Pilot Study of Systemic Inflammatory and Transcriptomic Responses in Patients Undergoing Open Retromuscular Ventral Hernia Repair
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Determine whether fascial closure tension correlates with systemic and peritoneal fluid cytokine activation.
研究概览
简要总结
This is a prospective, observational translational study of patients undergoing major abdominal wall reconstruction with primary fascial closure. The project integrates perioperative cytokine profiling, direct measurement of intra-abdominal pressure, and detailed clinical outcomes to define the biologic and physiologic consequences of high-tension closure.
The study includes three cohorts: 1) Healthy controls (N=5), 2) High-tension fascial closure AWR patients (N=10), 3) Low-tension fascial closure AWR patients (N=10). Fascial closure tension will not be altered for the purpose of the study and will be determined by the operating surgeon as part of routine clinical decision-making.
详细描述
Major abdominal wall reconstruction (AWR) for large ventral hernias is among the most physiologically demanding procedures performed in general surgery. These patients often have a history of multiple prior abdominal operations, chronically altered abdominal wall mechanics and significant loss of domain. Reduction of visceral contents and abdominal wall reconstruction frequently require high-tension closure, resulting in an abrupt increase in intra-abdominal pressure (IAP) that impairs diaphragmatic excursion, reduces splanchnic perfusion, causes renal venous congestion and induces global physiologic stress. Consequently, these patients face a high risk of postoperative complications including respiratory failure, renal dysfunction, and prolonged intensive care unit (ICU) stays.
A critical gap in AWR research is the lack of characterization of the biologic inflammatory and cytokine responses associated with high-tension abdominal wall closure. This gap stands in contrast to robust evidence from the trauma and critical care literature demonstrating that cytokine activation correlates with injury severity and contributes to organ dysfunction and postoperative morbidity.
Defining the inflammatory and cytokine signaling pathways activated during high-tension closure would provide a framework to inform operative planning and perioperative management, particularly in patients with significant comorbidities who may be less tolerant to postoperative physiologic stress. These insights would enable validation of current techniques and establish the foundation for future interventional trials targeting inflammatory pathways to improve postoperative outcomes. The Digestive Health Institute at Northwestern University is uniquely positioned to support this translational research, bridging surgical physiology, inflammation, and patient outcomes.
The investigators hypothesize that:
- Major abdominal wall reconstruction induces a trauma-like systemic inflammatory response characterized by elevations in GM-CSF, IFN-Gamma, IL-1, IL-2, IL-5, IL-6, IL-8, and TNF-alpha with a concomitant decrease in the anti-inflammatory cytokines, IL-4 and IL-10.
- Increased intra-abdominal pressure (IAP) following high-tension closure amplifies cytokine activation and is associated with early postoperative organ dysfunction and increased postoperative complications.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Surgical Participants
- •Adults aged 18 years or older
- •Scheduled to undergo open retromuscular ventral hernia repair
- •Able to provide written informed consent Healthy Control Participants
- •Adults aged 18 years or older
- •No known inflammatory, autoimmune, or immunologic disease
- •Able to provide written informed consent
排除标准
- •Emergent or urgent cases
- •Pregnancy
- •Chronic systemic steroid use or immunosuppressive therapy
- •Active infection at the time of enrollment
- •Known autoimmune or inflammatory disease
- •End-stage organ failure
- •Abdominal surgery within the preceding 60 days
研究组 & 干预措施
High tension group
Massive incisional ventral hernias with loss of domain undergoing open ventral hernia repair with transversus abdominis release with placement of mesh and closure of fascia under high tension.
干预措施: Not applicable- observational study (Other)
Low tension group
Incisional ventral hernias undergoing open ventral hernia repair with transversus abdominis release with placement of mesh and closure of fascia under low tension.
干预措施: Not applicable- observational study (Other)
Control
Healthy human subjects
结局指标
主要结局
Determine whether fascial closure tension correlates with systemic and peritoneal fluid cytokine activation.
时间窗: Baseline through postoperative day 5
Blood and peritoneal fluid will be collected at baseline (intra-operative), immediately following fascial closure and on postoperative days 1, 3, and 5. Serum cytokine concentrations of GM-CSF, IFN-gamma, IL-1, IL-2, IL-5, IL-6, IL-8, and TNF-alpha (inflammatory); IL-4 and IL-10 (anti-inflammatory) will be measured via multiplex immunoassays (Luminex). Cytokine area under the curve will also be calculated to allow analysis of total cytokine exposure over time.
次要结局
- Differences in peripheral blood mononuclear cells and peritoneal macrophage transcriptomic signatures via bulk RNA sequencing between baseline profiles from healthy control subjects, high-tension and low-tension abdominal wall closures.(Baseline through postoperative day 5)
- Differences in peak intra-abdominal values, intra-abdominal hypertension grading, abdominal perfusion pressure, plateau pressure between baseline profiles from healthy control subjects, high-tension and low-tension abdominal wall closures.(Baseline through postoperative day 5)
- Incidence of respiratory compromise(From surgery through hospital discharge (up to 30 days))
- Incidence of acute kidney injury(From surgery through hospital discharge (up to 30 days))
- Incidence of vasopressor use(From surgery through hospital discharge (up to 30 days))
- Incidence of postoperative ileus(From surgery through hospital discharge (up to 30 days))
- Incidence of wound complications(From surgery through hospital discharge (up to 30 days))
- ICU length of stay(From surgery through hospital discharge (up to 30 days))
- Hospital length of stay(From surgery through hospital discharge (up to 30 days))
研究者
Megan Melland-Smith
Principal Investigator
Northwestern University