Funded both intramurally and by external government agencies and commercial entities, SCIRC has a recognized obligation to fully disseminate the products of its research, consistent with its contractual assurances. To achieve these goals, SCIRC has teamed up with the Biorepository to serve as its “good faith” representative to administer the release of both deidentified data and archived biological samples.
About this archive
The SCIRC was created as a University of Florida-codified center in 2016 with the expressed goal to further our understanding of the immunological consequences of critical illness, particularly sepsis, trauma and perioperative injury.
For research funded by the Public Health Service and the Department of Health and Human Services, these agreements require that original de-identified clinical data and archived biological samples be made available to the general scientific community in a rapid and easily attainable manner.
Deidentified clinical data and archival samples will be released consistent with the policies of the CTSI Biorepository, and are independent of any input from SCIRC. These samples will be stored at the Biorepository and made available for researchers to use during and after the studies are completed. General policies regarding the requirement(s) for material transfer agreements, and any costs associated with the identification, removal and transport of biological samples are detailed in the CTSI Biorepository general policies.
Studies with available specimens
P50 GM-111182-05, PICS: A New Horizon in Surgical Critical Care
This is a prospective, observational long-term analysis of hospitalized patients with surgical sepsis1,2. Data and blood samples were collected from a single-center prospective 1-year longitudinal cohort study (NCT02276417) of critically ill surgical patients.
The study included 363 septic patients hospitalized in a 48-bed surgical intensive care unit (ICU) at a quaternary care academic hospital between January, 2015, and January, 2020. Ethics approval was obtained from the University of Florida Institutional Review Board (#201400611). Informed consent was obtained from each subject or their surrogate decision-maker. Detailed study cohort design and protocols utilized by the University of Florida (UF) Sepsis and Critical Illness Research Center (SCIRC) program have been published previously3,4; Outcome variables included 30, 90, 180 day and one-year mortality, development of chronic critical illness and incidence of secondary infections. Clinical data, inflammatory mediator data, flow cytometry, and selected transcriptomic data are available.
Because the study was not prospectively designed to collect additional samples for archival, only a very limited number of blood samples are available.
R01 GM-139046-01: Stratifying Patient Immune Endotypes in Sepsis (SPIES Study)
This is a prospective, observational, multicenter study (UF SCIRC, Washington University of St Louis, Department of Anesthesiology and the University of Cincinnati Department of Surgery) enrolling 270 patients with sepsis (using Sepsis-3 criteria) compared to 90 patients with critical illness without sepsis and 30 healthy subjects.
At 1, 4 and 7 days, and weekly thereafter post sepsis diagnosis, blood samples will be obtained and blood T-cell and monocyte production of IFN-gamma and TNF-alpha, respectively, will be determined by ELISpot5,6. In addition, samples will be obtained for other biomarkers, including plasma proteins (IL-6 and sPD-L1), CD14+cell expression of HLA-DR, total lymphocyte count and whole blood genomics. Secondary infections will be the primary clinical index of outcome7, with secondary indices including hospital readmission, and 180 day mortality. In addition, we will evaluate in this ELISpot platform the ex vivo response of IFN-gamma production by T-cells and TNF-alpha production by monocytes stimulated with varying concentrations of IL-7, anti-PD-1 mAb, anakinra, nivolumab, or dexamethasone, using a randomized block design. These immune adjuvants are currently under consideration as potential therapeutics for sepsis patients. This application proposes the validation of a novel functional bioassay to identify patients who would benefit from immunotherapy, and to identify different immune therapies that would benefit the individual patient.
As of September 1, 2021, 95 subjects have been enrolled since enrollment began in January, 2021, and data and archived samples will be available after October 1, 2021.
R01 GM-104481-04: Validation of a Genomics Based Prognostic in Severe Trauma
We propose that a significant proportion of patients who would generally meet the inclusion criteria for a study of severely injured patients, are not in need of immunomodulatory therapy, and are not only unlikely to benefit but also suffer direct toxicity from such therapies. In contrast, there exists a subset of patients who are going to have a protracted clinical course, and would benefit from interventional therapies with biological‐response modifiers. We believe that we have developed such a prospective genomic test8.
A prospective, observational cohort study of 127 severe trauma patients was conducted between October 2013 and August 2016 at 2 United States Level 1-trauma centers: SCIRC UFHealth Shands Hospital, Gainesville, Florida, and Harborview Medical Center, Seattle, Washington9. The Institutional Review Board of each institution granted approval prior to study initiation, and signed informed consent was obtained from the patient and/or their legally appointed representative. The study was prospectively registered with clinicaltrials.gov (NCT 01810328). In the trauma cohort, EDTA-anticoagulated blood samples were collected within 12 hours and at 24 hours following the traumatic insult. Gene expression analysis was conducted on the NanoString nCounter gene expression platform (NanoString Flex) using a custom code set consisting of a 63-gene panel as previously described.
Clinical data, inflammatory mediator data, and selected transcriptomic data are available. Because the study was not prospectively designed to collect additional samples for archival, only a very limited number of blood samples are available.
RM1 GM-139690-01: Dysfunctional Myelopoiesis and Myeloid-Derived Suppressor Cells in Sepsis Pathobiology
Earlier recognition of sepsis and improved implementation of best practices have significantly reduced in-hospital mortality over the past decade. As in-hospital survival has improved, the number of patients who do not fully recover has dramatically increased; nearly 30% of surgical sepsis patients will never fully recover and nearly one-third of these patients will die within 6 months1. Currently, one important critical question that vexes medical practitioners is: why do some surgical sepsis patients rapidly recover while others have poor long-term outcomes? The overarching hypothesis is that the consequences of surgical sepsis (death and poor quality of life) are the result of an unresolving host leukocyte dyscrasia, similar to other chronic conditions such as cancer and autoimmune disease10. Specifically, the preferential expansion and self-perpetuation of myeloid-derived suppressor cells (MDSCs), propagated in part through epigenetic changes in both bone marrow (BM) progenitors and MDSCs11, drives non-acute infectious and noninfectious complications after sepsis. This prospective observational study in 300 septic patients will investigate the underlying mechanisms that drive dysfunctional myelopoiesis, expansion of MDSC populations, suppressed T-cell quantities/function, and the development of patient’s immunosuppressive/ inflammatory endotypes. We will primarily focus on how MDSC expansion evolves over time in surgical sepsis patients who do or do not rapidly recover; how myelopoiesis is regulated transcriptionally and epigenetically in the bone marrow of trauma patients who are at high risk of developing sepsis. Using the established clinical infrastructure of the Sepsis and Critical Illness Research Center (SCIRC), a team science approach is being employed with collaborating PI’s coming from multiple clinical and basic science disciplines.
Enrollment is beginning September 1, 2021 (IRB#202100559), and deidentified data and archived samples will be available after January 1, 2022. Registration of the study with clinicaltrials.gov is pending.
How to access specimens
- Call or e-mail the CTSI Biorepository Client Coordinator, Erin Kelly, (352) 273-6138, firstname.lastname@example.org or email the Biorepository general email at Biorepository@pathology.ufl.edu
- Biorepository will provide an inventory report of available specimens as well as a quote for the cost of retrieving them
- Implement a Material Transfer Agreement between the University of Florida and your institution
- Submit a Statement of Work (SOW) for the specific specimens of interest
Additional considerations for researchers:
- Depending on the availability of specimens, there may be limitations on how many samples or volumes of each sample researchers can access
- All researchers may access these specimens after completing the appropriate steps for acquisition
CTSI Biorepository Client Coordinator | 352-273-6138
Researchers may also contact the Biorepository directly at Biorepository@pathology.ufl.edu
¹ Scott C Brakenridge, Philip A Efron, Michael C Cox , Julie A Stortz , Russell B Hawkins, Gabriela Ghita, Anna Gardner, Alicia M Mohr, Stephen D Anton, Lyle L Moldawer, Frederick A Moore. Current Epidemiology of Surgical Sepsis: Discordance Between Inpatient Mortality and 1-year Outcomes. Ann Surg. 2019 Sep;270(3):502-510.
² McKenzie K Hollen, Julie A Stortz, Dijoia Darden, Marvin L Dirain, Dina C Nacionales, Russell B Hawkins, Michael C Cox, Maria-Cecilia Lopez, Jaimar C Rincon, Ricardo Ungaro, Zhongkai Wang, Quran Wu, Babette Brumback, Marie-Pierre L Gauthier, Michael Kladde, Christiaan Leeuwenburgh, Mark Segal, Azra Bihorac, Scott Brakenridge, Frederick A Moore, Henry V Baker, Alicia M Mohr, Lyle L Moldawer, Philip A Efron. Myeloid-derived suppressor cell function and epigenetic expression evolves over time after surgical sepsis. Crit Care. 2019 Nov 13;23(1):355.
³ Tyler J Loftus, Juan C Mira, Tezcan Ozrazgat-Baslanti, Gabriella L Ghita, Zhongkai Wang, Julie A Stortz, Babette A Brumback, Azra Bihorac, Mark S Segal, Stephen D Anton, Christiaan Leeuwenburgh, Alicia M Mohr, Philip A Efron, Lyle L Moldawer, Frederick A Moore, Scott C Brakenridge. Sepsis and Critical Illness Research Center investigators: protocols and standard operating procedures for a prospective cohort study of sepsis in critically ill surgical patients BMJ Open. 2017 Aug 1;7(7):e015136.
4 Chasen A Croft, Frederick A Moore, Philip A Efron, Peggy S Marker, Andrea Gabrielli, Lynn S Westhoff, Lawrence Lottenberg, Janeen Jordan, Victoria Klink, R Matthew Sailors, Bruce A McKinley. Computer versus paper system for recognition and management of sepsis in surgical intensive care. J Trauma Acute Care Surg. 2014 Feb;76(2):311-7.
5 Monty B Mazer, Charles C Caldwel, Jodi Hanson, Daniel Mannion, Isaiah R Turnbull, Anne Drewry, Dale Osborne, Andrew Walton, Tessa Blood, Lyle L Moldawer, Scott Brakenridge, Kenneth E Remy, Richard S Hotchkiss. A Whole Blood Enzyme-Linked Immunospot Assay for Functional Immune Endotyping of Septic Patients. J Immunol. 2021 Jan 1;206(1):23-36.
6 Kenneth E Remy, Monty Mazer, David A Striker, Ali H Ellebedy, Andrew H Walton, Jacqueline Unsinger, Teresa M Blood, Philip A Mudd, Daehan J Yi, Daniel A Mannion, Dale F Osborne, R Scott Martin, Nitin J Anand, James P Bosanquet, Jane Blood, Anne M Drewry, Charles C Caldwell, Isaiah R Turnbull, Scott C Brakenridge, Lyle L Moldwawer, Richard S Hotchkiss. Severe immunosuppression and not a cytokine storm characterizes COVID-19 infections. JCI Insight. 2020 Sep 3;5(17):e140329.
7 Julie A Stortz, Michael C Cox, Russell B Hawkins, Gabriela L Ghita, Babette A Brumback, Alicia M Mohr, Lyle L Moldawer, Philip A Efron, Scott C Brakenridge, Frederick A Moore. Phenotypic heterogeneity by site of infection in surgical sepsis: a prospective longitudinal study. Crit Care. 2020 May 7;24(1):203.
8 Steven L Raymond, Russell B Hawkins, Zhongkai Wang, Juan C Mira, Julie A Stortz, Feifei Han, Jennifer D Lanz, Laura V Hennessy, Babette A Brumback, Henry V Baker, Philip A Efron, Scott C Brakenridge, Wenzhong Xiao, Ronald G Tompkins, Joseph Cuschieri, Frederick A Moore, Ronald V Maier, Lyle L Moldawer. Prospective Validation of a Transcriptomic Metric in Severe Trauma. Ann Surg. 2020 May;271(5):802-810.
9 Juan C Mira, Joseph Cuschieri, Tezcan Ozrazgat-Baslanti, Zhongkai Wang, Gabriela L Ghita, Tyler J Loftus, Julie A Stortz, Steven L Raymond, Jennifer D Lanz, Laura V Hennessy, Babette Brumback, Philip A Efron, Henry V Baker, Frederick A Moore, Ronald V Maier, Lyle L Moldawer, Scott C Brakenridge. The Epidemiology of Chronic Critical Illness After Severe Traumatic Injury at Two Level-One Trauma Centers. Crit Care Med. 2017 Dec;45(12):1989-1996.
10 Brittany P Fenner, D B Darden, Lauren S Kelly, Jaimar Rincon, Scott C Brakenridge, Shawn D Larson, Frederick A Moore, Philip A Efron, Lyle L Moldawer. Immunological Endotyping of Chronic Critical Illness After Severe Sepsis. Front Med (Lausanne). 2021 Feb 15;7:616694. doi: 10.3389/fmed.2020.616694. eCollection 2020.
11 McKenzie K Hollen, Julie A Stortz, Dijoia Darden, Marvin L Dirain, Dina C Nacionales, Russell B Hawkins, Michael C Cox, Maria-Cecilia Lopez, Jaimar C Rincon, Ricardo Ungaro, Zhongkai Wang, Quran Wu, Babette Brumback, Marie-Pierre L Gauthier, Michael Kladde, Christiaan Leeuwenburgh, Mark Segal, Azra Bihorac, Scott Brakenridge, Frederick A Moore, Henry V Baker, Alicia M Mohr, Lyle L Moldawer, Philip A Efron. Myeloid-derived suppressor cell function and epigenetic expression evolves over time after surgical sepsis. Crit Care. 2019 Nov 13;23(1):355. doi: 10.1186/s13054-019-2628-x