The Role of Brain-Bone Marrow-Gut Interaction Following Major Trauma

Обзор

Traumatic injury followed by critical illness provokes pathophysiologic changes in the bone marrow and the gut that contribute to persistent anemia and changes in the microbiome which significantly impact long-term recovery. This project will define the interactions between the stress, chronic inflammation, bone marrow dysfunction, and an altered microbiome which will provide a strong foundation for future clinical interventions to help improve outcomes following severe trauma.

Подробное описание

Trauma remains the leading cause of death among people younger than 46 years of age and is the leading cause of years of potential life lost among those younger than 65. With more lives saved, trauma morbidity has increased, which has consequently revealed a lack of understanding of the impact of trauma survivorship on the patients' quality of life and long-term recovery. Severe injury when followed by chronic critical illness leads to persistent anemia, and the use of blood transfusions is associated with a linear increase in infectious complications. These conditions are due to prolonged bone marrow dysfunction associated with an exaggerated catecholamine response, chronic stress, and systemic inflammation. Our laboratory has conducted human research to establish that there are unique bone marrow transcriptomic differences related to inflammation, the innate immune response, and known inhibitors of erythropoiesis following trauma. The laboratory has also discovered that chronic stress after trauma contributes to persistent anemia with impaired iron and erythropoietin function along with the prolonged loss of hematopoietic stem progenitor cells (HSPC) from the bone marrow. Chronic stress after trauma also induces an altered microbiome with decreased alpha and beta diversity and changes in microbial composition leading to a persistent 'pathobiome'. All of these factors influence outcomes. We hypothesize that there is a unifying interaction between stress, inflammation, and the microbiome and this has an overall role in the regulation of HSPC and erythroid progenitor cell fate and function following trauma and critical illness. Therefore, the overarching goal for this study is to build upon this foundation and expand our understanding of HSPC fate and function following trauma, including examining interventions aimed at reducing stress/inflammation and restoring the microbiome, thus, improving long-term outcomes.

Вмешательства

• Другое Data and tissue collection
  Collection of bone marrow, blood, feces, medical record data, and patient response surveys.

Первичные конечные точки

• Link the changes in HSPC and erythroid progenitor cell fate and function with sympathetic stress-induced changes establishing brain-bone marrow communication following trauma. [Срок оценки: 3 years]
• Determine the connection between changes in the microbiome with sympathetic stress-induced changes establishing gut-brain communication following trauma. [Срок оценки: 3 years]
• Link changes in the microbiome with altered HSPC and erythroid progenitor cells fate establishing gut-bone marrow communication following trauma [Срок оценки: 3 years]

Критерии участия

Severe Trauma Cohort

Критерии включения

• All adults (age ≥18).
• Blunt trauma with an injury severity score > 15 and a long bone or pelvic fracture requiring open reduction internal fixation or intramedullary fixation
• Blunt trauma patients with shock, defined by either a systolic BP (SBP) <90 mm Hg or base deficit (BD) ≥5 meq or lactate ≥ 2 mmol/L or active red blood cell or whole blood transfusion within 6h or arrival

Критерии исключения

• Patients not expected to survive greater than 48 hours
• Prisoners
• Pregnancy
• Previous bone marrow transplantation
• Patients receiving chronic corticosteroids or immunosuppression therapies
• Patients with End Stage Renal Disease
• Patients with any pre-existing hematological disease
• Surgery for repair of injury is greater than seven days after admission to the hospital for trauma
• Burn injury greater than 20% TBSA

Elective Hip Cohort

Критерии включения

• All adults (age ≥55).
• Patient undergoing elective hip repair for non-infectious reasons.
• Ability to obtain Informed Consent prior to operation.

Критерии исключения

• Patients not expected to survive greater than 48 hours
• Prisoners
• Pregnancy
• Previous bone marrow transplantation
• Patients receiving chronic corticosteroids or immunosuppression therapies
• Patients with End Stage Renal Disease
• Patients with any pre-existing hematological disease

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

США · 3 центра

• UF Academic Research Building — Gainesville
• UF Health at Shands Hospital — Gainesville
• UF Laboratory of Inflammation Biology and Surgical Science and Shands Hospital at UF — Gainesville

Идентификаторы

NCT: NCT06606119 · IRB202400903 · 1R35GM152216-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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