RecruitingNot ApplicableNCT02577731

Hematopoietic Stem Cell Dysfunction in the Elderly After Severe Injury

Hematopoietic Stem Cell Dysfunction in the Elderly After Severe Injury: Chronic Stress and Anemia Recovery Following Major Trauma

Sponsor

University of Florida

Enrollment

400 participants

Start Date

Jan 1, 2014

Study Type

INTERVENTIONAL

Conditions

Trauma Injury

Summary

Traumatic injury is a leading cause of morbidity and mortality in young adults, and remains a substantial economic and health care burden. Despite decades of promising preclinical and clinical investigations in trauma, investigators understanding of these entities is still incomplete, and few therapies have shown success. During severe trauma, bone marrow granulocyte stores are rapidly released into the peripheral circulation. This release subsequently induces the expansion and repopulation of empty or evacuated space by hematopoietic stem cells (HSCs). Although the patient experiences an early loss of bone marrow myeloid-derived cells, stem cell expansion is largely skewed towards the repopulation of the myeloid lineage/compartment. The hypothesis is that this 'emergency myelopoiesis' is critical for the survival of the severely traumatized and further, failure of the emergency myelopoietic response is associated with global immunosuppression and susceptibility to secondary infection. Also, identifying the release of myeloid derived suppressor cells (MDSCs) in the circulation of human severe trauma subjects. This process is driven by HSCs in the bone marrow of trauma subjects. Additionally, MDSCs may have a profound effect on the nutritional status of the host. The appearance of these MDSCs after trauma is associated with a loss of muscle tissue in these subjects. This muscle loss and possible increased catabolism have huge effects on long term outcomes for these subjects. It is the investigator's goal to understand the differences that occur in these in HSCs and muscle cells as opposed to non-injured and non-infected controls. This work will lead to a better understanding of the myelopoietic and catabolic response following trauma.

Eligibility

Min Age: 18 Years

Inclusion Criteria14

Severe Trauma Population
All adults (age ≥18 to 54)
Blunt and/or penetrating trauma resulting in long bone or pelvic fractures requiring ORIF or closed reduction percutaneous pinning (CRPP).
Blunt and/or penetrating trauma patient with either:
hemorrhagic shock defined by: i. systolic BP (SBP) ≤ 90 mmHg or ii. mean arterial pressure≤ 65 mmHg or iii. base deficit (BD) ≥ 5 meq or iv. lactate ≥ 2
Or injury severity score (ISS) greater than or equal to 15.
All adults (age 55 and older) require:
Blunt and/or penetrating trauma resulting in log bone or pelvic fractures requiring ORIF or CRPP
Either hemorrhagic shock defined by: i. Systolic BP (SBP) ≤ 90 mmHg or ii. Mean arterial pressure ≤ 65 mmHg or iii. Base deficit (BD) ≥5 meq or iv. Lactate ≥ 2
Or Injury Severity Score (ISS) greater than or equal to 15.
Ability to obtain Informed Consent prior to OR repair of injury.
All adults (age ≥18)
Patient undergoing elective hip repair for non-infectious reasons.
Ability to obtain Informed Consent prior to operation.

Exclusion Criteria14

Patients not expected to survive greater than 48 hours.
Prisoners.
Pregnancy.
Patients receiving chronic corticosteroids or immunosuppression therapies.
Previous bone marrow transplantation.
Patients with End Stage Renal Disease.
Patients with any pre-existing hematological disease.
Elective Hip Repair Population
Pregnancy.
Prisoners.
Patients receiving chronic corticosteroids or immunosuppression therapies.
History of receiving Chemotherapy or Radiation within the last 6 months
Previous bone marrow transplantation
\. Patients with End Stage Renal Disease 8. Patients with any pre-existing hematological disease

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Interventions

OTHERBone marrow collection

Bone marrow will be collected from the patient at time of orthopedic repair in the operating room. A second sample may be collected if the patient is required to return to the operating room for further repair of orthopedic injury.

OTHERBlood collection

Blood sample collection will be collected from the patient at time of orthopedic repair in the operating room. A second sample may be collected if the patient is required to return to the operating room for further repair of orthopedic injury.

OTHERClinical data collection

Clinical data collection will encompass demographic information, past and present medical records, laboratory, microbiology, and all other test results, x-ray, CT, MRI, US and all other imaging test results, records about any medication received during admission, records of physical exam during admission, records of all vital signs and hemodynamic monitoring during admission, records of any procedure or intervention during admission, records of any procedure or intervention during hospital admission, condition at the discharge and discharge facility.