TY - JOUR
T1 - Preoperative protein profiles in cerebrospinal fluid in elderly hip fracture patients at risk for delirium
T2 - A proteomics and validation study
AU - Westhoff, Dunja
AU - Witlox, Joost
AU - van Aalst, Corneli
AU - Scholtens, Rikie M.
AU - de Rooij, Sophia E
AU - van Munster, Barbara C
AU - de Jonghe, Jos F M
AU - Houdijk, Alexander P J
AU - Eikelenboom, Piet
AU - van Westerloo, David J
AU - van de Beek, Diederik
AU - van Gool, Willem A
AU - Koenderman, Leo
PY - 2015/12
Y1 - 2015/12
N2 - BACKGROUND: A neuroinflammatory response is suggested to play an important role in delirium, a common complication in older hospitalized patients. We examined whether hip fracture patients who develop postoperative delirium have a different proteome in cerebrospinal fluid (CSF) prior to surgery.METHODS: Patients (≥ 75 years) were admitted for hip fracture surgery. CSF was collected during spinal anaesthesia; proteins were separated using gel electrophoresis and identified with mass spectrometry. We compared the proteome of patients with and without postoperative delirium. Findings were validated in an independent, comparable cohort using immuno-assays.RESULTS: In the derivation cohort 53 patients were included, 35.8% developed postoperative delirium. We identified differences in levels of eight CSF proteins between patients with and without subsequent delirium: complement factor C3, contactin-1, fibulin-1 and I-beta-1,3-N-acetylglucosaminyltransferase were significantly lower in patients with postoperative delirium, while neural cell adhesion molecule-2, fibrinogen, zinc-α-2-glycoprotein and haptoglobin levels were significantly higher. In the validation cohort 21.2% of 52 patients developed postoperative delirium. Immuno-assays confirmed contactin-1 results although not statistically significant. Complement factor C3 was significantly higher in patients with postoperative delirium.CONCLUSION: Our results show the complexity of pathophysiological mechanisms involved in delirium and emphasizes the need of independent validation of findings.GENERAL SIGNIFICANCE: This study highlights the challenges and inconsistent findings in studies of delirium, a serious complication in older patients. We analysed proteins in CSF, the most proximal fluid to the brain. All patients were free from delirium at the time of sampling.
AB - BACKGROUND: A neuroinflammatory response is suggested to play an important role in delirium, a common complication in older hospitalized patients. We examined whether hip fracture patients who develop postoperative delirium have a different proteome in cerebrospinal fluid (CSF) prior to surgery.METHODS: Patients (≥ 75 years) were admitted for hip fracture surgery. CSF was collected during spinal anaesthesia; proteins were separated using gel electrophoresis and identified with mass spectrometry. We compared the proteome of patients with and without postoperative delirium. Findings were validated in an independent, comparable cohort using immuno-assays.RESULTS: In the derivation cohort 53 patients were included, 35.8% developed postoperative delirium. We identified differences in levels of eight CSF proteins between patients with and without subsequent delirium: complement factor C3, contactin-1, fibulin-1 and I-beta-1,3-N-acetylglucosaminyltransferase were significantly lower in patients with postoperative delirium, while neural cell adhesion molecule-2, fibrinogen, zinc-α-2-glycoprotein and haptoglobin levels were significantly higher. In the validation cohort 21.2% of 52 patients developed postoperative delirium. Immuno-assays confirmed contactin-1 results although not statistically significant. Complement factor C3 was significantly higher in patients with postoperative delirium.CONCLUSION: Our results show the complexity of pathophysiological mechanisms involved in delirium and emphasizes the need of independent validation of findings.GENERAL SIGNIFICANCE: This study highlights the challenges and inconsistent findings in studies of delirium, a serious complication in older patients. We analysed proteins in CSF, the most proximal fluid to the brain. All patients were free from delirium at the time of sampling.
KW - Journal Article
U2 - 10.1016/j.bbacli.2015.10.002
DO - 10.1016/j.bbacli.2015.10.002
M3 - Article
C2 - 26675981
SN - 1555-9041
VL - 4
SP - 115
EP - 122
JO - Clinical Journal of the American Society of Nephrology
JF - Clinical Journal of the American Society of Nephrology
ER -