Identification of Neutrophil Phenotype Categories in Geriatric Hip Fracture Patients Aids in Personalized Medicine

Overview

Journal OTA Int

Date 2023 Dec 28

PMID 38152436

Authors

Thomas M P Nijdam

Bernard N Jukema

Emma J de Fraiture

Roy Spijkerman

Henk Jan Schuijt

Marcia Spoelder

Coen C W G Bongers

Maria T E Hopman

Leo Koenderman

Falco Hietbrink

Detlef van der Velde

Affiliations

Soon will be listed here.

Abstract

Objectives: The number of geriatric hip fracture patients is high and expected to rise in the coming years, and many are frail and at risk for adverse outcomes. Early identification of high-risk patients is crucial to balance treatment and optimize outcome, but remains challenging. Previous research in patients with multitrauma suggested that neutrophil phenotype analysis could aid in early identification of high-risk patients. This pilot study investigated the feasibility and clinical value of neutrophil phenotype analysis in geriatric patients with a hip fracture.

Methods: A prospective study was conducted in a regional teaching hospital in the Netherlands. At the emergency department, blood samples were collected from geriatric patients with a hip fracture and analyzed using automated flow cytometry. Flow cytometry data were processed using an automated clustering algorithm. Neutrophil activation data were compared with a healthy control cohort. Neutrophil phenotype categories were assessed based on two-dimensional visual assessment of CD16/CD62L expression.

Results: Blood samples from 45 geriatric patients with a hip fracture were included. Neutrophils showed an increased activation profile and decreased responsiveness to formyl peptides when compared to healthy controls. The neutrophil phenotype of all patients was categorized. The incidence of severe adverse outcome was significantly different between the different categories ( = 0.0331). Moreover, patients with neutrophil phenotype category 0 developed no severe adverse outcomes.

Conclusions: Using point-of-care fully automated flow cytometry to analyze the neutrophil compartment in geriatric hip fracture patients is feasible and holds clinical value in determining patients at risk for adverse outcome. This study is a first step toward immuno-based precision medicine for identifying geriatric hip fracture patients that are deemed fit for surgery.

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References

Hietbrink F, Koenderman L, Rijkers G, Leenen L . Trauma: the role of the innate immune system. World J Emerg Surg. 2006; 1:15. PMC: 1481567. DOI: 10.1186/1749-7922-1-15. View

Veronese N, Maggi S . Epidemiology and social costs of hip fracture. Injury. 2018; 49(8):1458-1460. DOI: 10.1016/j.injury.2018.04.015. View

Spijkerman R, Hesselink L, Hellebrekers P, Vrisekoop N, Hietbrink F, Leenen L . Automated flow cytometry enables high performance point-of-care analysis of leukocyte phenotypes. J Immunol Methods. 2019; 474:112646. DOI: 10.1016/j.jim.2019.112646. View

Kolaczkowska E, Kubes P . Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol. 2013; 13(3):159-75. DOI: 10.1038/nri3399. View

Wang J . Neutrophils in tissue injury and repair. Cell Tissue Res. 2018; 371(3):531-539. PMC: 5820392. DOI: 10.1007/s00441-017-2785-7. View

Hesselink L, Spijkerman R, van Wessem K, Koenderman L, Leenen L, Huber-Lang M . Neutrophil heterogeneity and its role in infectious complications after severe trauma. World J Emerg Surg. 2019; 14:24. PMC: 6542247. DOI: 10.1186/s13017-019-0244-3. View

de Fraiture E, Bongers S, Jukema B, Koenderman L, Vrisekoop N, van Wessem K . Visualization of the inflammatory response to injury by neutrophil phenotype categories : Neutrophil phenotypes after trauma. Eur J Trauma Emerg Surg. 2022; 49(2):1023-1034. PMC: 10175373. DOI: 10.1007/s00068-022-02134-3. View

Spijkerman R, Hesselink L, Bongers S, van Wessem K, Vrisekoop N, Hietbrink F . Point-of-Care Analysis of Neutrophil Phenotypes: A First Step Toward Immuno-Based Precision Medicine in the Trauma ICU. Crit Care Explor. 2020; 2(7):e0158. PMC: 7371075. DOI: 10.1097/CCE.0000000000000158. View

Hietbrink F, Koenderman L, Althuizen M, Pillay J, Kamp V, Leenen L . Kinetics of the innate immune response after trauma: implications for the development of late onset sepsis. Shock. 2013; 40(1):21-7. DOI: 10.1097/SHK.0b013e318295a40a. View

10.

Groeneveld K, Koenderman L, Warren B, Jol S, Leenen L, Hietbrink F . Early decreased neutrophil responsiveness is related to late onset sepsis in multitrauma patients: An international cohort study. PLoS One. 2017; 12(6):e0180145. PMC: 5493351. DOI: 10.1371/journal.pone.0180145. View

11.

Ferrucci L, Fabbri E . Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol. 2018; 15(9):505-522. PMC: 6146930. DOI: 10.1038/s41569-018-0064-2. View

12.

Gullberg B, Johnell O, Kanis J . World-wide projections for hip fracture. Osteoporos Int. 1997; 7(5):407-13. DOI: 10.1007/pl00004148. View

13.

Jette A, Harris B, Cleary P, Campion E . Functional recovery after hip fracture. Arch Phys Med Rehabil. 1987; 68(10):735-40. View

14.

van de Ree C, de Jongh M, Peeters C, de Munter L, Roukema J, Gosens T . Hip Fractures in Elderly People: Surgery or No Surgery? A Systematic Review and Meta-Analysis. Geriatr Orthop Surg Rehabil. 2017; 8(3):173-180. PMC: 5557195. DOI: 10.1177/2151458517713821. View

15.

Johnell O . The socioeconomic burden of fractures: today and in the 21st century. Am J Med. 1997; 103(2A):20S-25S; discussion 25S-26S. DOI: 10.1016/s0002-9343(97)90023-1. View

16.

Dizdarevic A, Farah F, Ding J, Shah S, Bryan A, Kahn M . A Comprehensive Review of Analgesia and Pain Modalities in Hip Fracture Pathogenesis. Curr Pain Headache Rep. 2019; 23(10):72. DOI: 10.1007/s11916-019-0814-9. View

17.

Ota K, Shimizu Y, Ichikawa H, Ueda M, Akiyama N, Higuchi C . Neutrophil activation in immunoadsorption. Ther Apher. 2000; 4(3):229-34. DOI: 10.1046/j.1526-0968.2000.00191.x. View

18.

Jukema B, Smit K, Hopman M, Bongers C, Pelgrim T, Rijk M . Neutrophil and Eosinophil Responses Remain Abnormal for Several Months in Primary Care Patients With COVID-19 Disease. Front Allergy. 2022; 3:942699. PMC: 9365032. DOI: 10.3389/falgy.2022.942699. View

19.

Botha A, Moore F, Moore E, Kim F, Banerjee A, Peterson V . Postinjury neutrophil priming and activation: an early vulnerable window. Surgery. 1995; 118(2):358-64; discussion 364-5. DOI: 10.1016/s0039-6060(05)80345-9. View

20.

Loggers S, Willems H, van Balen R, Gosens T, Polinder S, Ponsen K . Evaluation of Quality of Life After Nonoperative or Operative Management of Proximal Femoral Fractures in Frail Institutionalized Patients: The FRAIL-HIP Study. JAMA Surg. 2022; 157(5):424-434. PMC: 8892372. DOI: 10.1001/jamasurg.2022.0089. View