NCT07667153尚未招募不适用

Myeloid Bias in the Bone Marrow of Septic Patients

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology0 个研究点目标入组 45 人开始时间: 2026年10月15日最近更新: 2026年9月24日

适应症

干预措施

试验速览

阶段: 不适用
状态: 尚未招募
发起方
入组人数: 45
主要终点: Percentage and Absolute Count of Hematopoietic Stem Cells (HSCs) in Bone Marrow

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者记录与标识符相似试验

研究概览

简要总结

Sepsis remains a leading cause of critical illness worldwide, yet the underlying mechanisms driving its profound and persistent immune dysfunction are incompletely understood. The bone marrow, as the birthplace of all immune cells, plays a central role in orchestrating systemic immune responses. Emerging evidence from animal models suggests that sepsis triggers emergency myeloid-biased hematopoiesis in the bone marrow, characterized by expansion of myeloid progenitors and myeloid-derived suppressor cells (MDSCs) at the expense of lymphoid and erythroid lineages. This bone marrow remodeling precedes peripheral immune alterations and may represent the initiating event of sepsis-induced immunosuppression. However, direct clinical evidence in humans is scarce. This prospective, single-center cohort study aims to systematically characterize bone marrow hematopoietic remodeling in patients with septic shock, compared to critically ill non-septic patients and healthy volunteers, and to determine whether the degree of myeloid lineage bias correlates with disease severity, immunosuppression, and adverse clinical outcomes.

This study will enroll three cohorts. Bone marrow aspirates and peripheral blood samples will be collected at 48-72 hours post-enrollment for flow cytometric immunophenotyping of hematopoietic stem/progenitor cells, MDSC subsets, and PD-L1 expression, as well as cytokine profiling and exploratory single-cell transcriptomics. Rectal swabs will be collected synchronously for 16S rRNA sequencing and untargeted metabolomics to investigate the association between gut microbiota, microbial metabolites, and bone marrow myeloid skewing, testing the gut-bone marrow-immune axis hypothesis. Clinical severity (SOFA/APACHE II), secondary infections, and 90-day mortality will be assessed to evaluate prognostic value. By integrating bone marrow hematopoiesis, gut microbiome, and clinical outcomes, this study seeks to provide novel mechanistic insights into sepsis-induced immunoparalysis and identify potential biomarkers or therapeutic targets for immune restoration.

研究设计

研究类型: Observational
观察模型: Cohort
时间视角: Prospective

入排标准

年龄范围: 18 Years 至 80 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 是

入选标准

•1. Inclusion Criteria
•(1) Sepsis-Associated Critical Illness Cohort
•Age 18-80 years, both genders;
•Meets the Sepsis-3.0 criteria: confirmed or suspected infection with an acute increase in SOFA score of ≥2 points;
•Admitted to the intensive care unit (ICU) for 48-72 hours at the time of enrolment;
•Expected ICU length of stay ≥7 days;
•Written informed consent provided by the patient or their legally authorized representative.
•(2) Non-Septic Critical Illness Cohort
•Age 18-80 years, both genders;
•Admitted to the ICU for 48-72 hours with a diagnosis of non-infectious critical illness, including but not limited to: (a) severe acute pancreatitis; (b) major trauma (Injury Severity Score ≥16); (c) post-major surgery (e.g., cardiovascular surgery, hepatectomy); (d) acute cerebrovascular disease (ischaemic stroke, intracerebral haemorrhage); (e) other critical conditions requiring ICU support;
•Expected ICU length of stay ≥7 days;
•Written informed consent provided by the patient or their legally authorized representative.
•(3) Healthy Volunteer Control Cohort
•Age 18-80 years, both genders.
•No acute or chronic medical history; recent health check-up results are normal.
•Normal complete blood count: white blood cell count, haemoglobin, and platelet count within the normal reference ranges;
•Willing and able to provide written informed consent.

排除标准

•(1) Sepsis-Associated Critical Illness Cohort
•Haematological disorders: previous or current primary haematological diseases affecting bone marrow haematopoiesis, including leukaemia, myelodysplastic syndromes, aplastic anaemia, multiple myeloma, lymphoma, etc;
•Active malignancy or receipt of chemotherapy/radiotherapy within the past 3 years;
•Immunosuppressed state: (a) use of immunosuppressive agents within the past 3 months (including glucocorticoids ≥0.5 mg/kg/day for ≥2 weeks); (b) history of solid organ or haematopoietic stem cell transplantation; (c) HIV infection or AIDS; (d) congenital immunodeficiency;
•Blood transfusion or bone marrow transplantation within the past 3 months;
•Severe chronic organ dysfunction: (a) Child-Pugh Class C liver disease; (b) end-stage renal disease (eGFR <30 mL/min) without regular dialysis;
•Abnormalities at the puncture site: infection, rash, trauma, or anatomical deformity at the posterior superior iliac spine;
•Pregnancy or breastfeeding;
•Moribund state with expected survival <24 hours;
•Participation in another interventional clinical trial within 3 months before or at enrolment;
•Refusal to sign informed consent by the patient or legal representative.
•(2) Non-Septic Critical Illness Cohort
•Evidence of infection: confirmed or suspected active infection (including pneumonia, intra-abdominal infection, urinary tract infection, bloodstream infection, etc.) within 48 hours of ICU admission;
•All other exclusion criteria listed for the Sepsis-Associated Critical Illness Cohort (items 1-10) apply.
•(3) Healthy Volunteer Control Cohort
•History of infection within the past 1 month;
•Abnormalities at the puncture site: infection, rash, trauma, or anatomical deformity at the posterior superior iliac spine;
•Pregnancy or breastfeeding.

研究组 & 干预措施

Sepsis-Associated Critical Illness Cohort

Patients admitted to the intensive care unit (ICU) with a confirmed or highly suspected infection and meeting the Sepsis-3 criteria (an acute change in Sequential Organ Failure Assessment [SOFA] score ≥ 2 points in the presence of infection).

干预措施: Bone marrow aspirate collection (Procedure)

Non-Septic Critical Illness Cohort

Critically ill patients admitted to the same ICU with an acute life-threatening condition that is not attributed to infection. Typical etiologies include severe trauma, major elective or emergency surgery (e.g., abdominal, or neurosurgical procedures), acute pancreatitis, or massive haemorrhage, all without any clinical or microbiological evidence of infection at enrolment.

干预措施: Bone marrow aspirate collection (Procedure)

Healthy Volunteer Control Cohort

Community-dwelling adults with no acute or chronic medical conditions that could affect haematopoiesis or immune function. They are recruited from the same geographical region and during the same calendar period to minimise seasonal and demographic biases.

干预措施: Bone marrow aspirate collection (Procedure)