scholarly journals Neuroinflammation in cognitive decline post-cardiac surgery (the FOCUS study): an observational study protocol

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e044062
Author(s):  
Annemieke M Peters van Ton ◽  
Harmke B. Duindam ◽  
Julia van Tuijl ◽  
Wilson WL Li ◽  
Hendrik-Jan Dieker ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Observational Study ◽  
Systemic Inflammation ◽  
Study Protocol ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Postoperative Cognitive Dysfunction ◽  
Translocator Protein ◽  
Surgical Trauma ◽  
Cerebral Mri

IntroductionPostoperative cognitive dysfunction occurs frequently after coronary artery bypass grafting (CABG). The underlying mechanisms remain poorly understood, but neuroinflammation might play a pivotal role. We hypothesise that systemic inflammation induced by the surgical trauma could activate the innate immune (glial) cells of the brain. This could lead to an exaggerated neuroinflammatory cascade, resulting in neuronal dysfunction and loss of neuronal cells. Therefore, the aims of this study are to assess neuroinflammation in vivo presurgery and postsurgery in patients undergoing major cardiac surgery and investigate whether there is a relationship of neuroinflammation to cognitive outcomes, changes to brain structure and function, and systemic inflammation.Methods and analysisThe FOCUS study is a prospective, single-centre observational study, including 30 patients undergoing elective on-pump CABG. Translocator protein (TSPO) positron emission tomography neuroimaging will be performed preoperatively and postoperatively using the second generation tracer 18F-DPA-714 to assess the neuroinflammatory response. In addition, a comprehensive cerebral MRI will be performed presurgery and postsurgery, in order to discover newly developed brain and vascular wall lesions. Up to 6 months postoperatively, serial extensive neurocognitive assessments will be performed and blood will be obtained to quantify systemic inflammatory responses and peripheral immune cell activation.Ethics and disseminationPatients do not benefit directly from engaging in the study, but imaging neuroinflammation is considered safe and no side effects are expected. The study protocol obtained ethical approval by the Medical Research Ethics Committee region Arnhem-Nijmegen. This work will be published in peer-reviewed international medical journals and presented at medical conferences.Trial registration numberNCT04520802.

scholarly journals Immune Dysfunction and Albumin-Related Immunity in Liver Cirrhosis

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Benjamin Wilde ◽  
Antonios Katsounas
Keyword(s):  
Liver Cirrhosis ◽  
Systemic Inflammation ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Significant Risk ◽  
Kidney Injury ◽  
Immune Dysfunction ◽  
Developed Countries ◽  
Bacterial Peritonitis ◽  
End Stage

Liver cirrhosis yearly causes 1.2 million deaths worldwide, ranking as the 10th leading cause of death in the most developed countries. High susceptibility to infections along with a significant risk for infection-related mortality justifies the description of liver cirrhosis as the world’s most common immunodeficiency syndrome. Liver cirrhosis is an end-stage organic disease hallmarked by a multifaceted immune dysfunction due to deterioration of antimicrobial recognition and elimination mechanisms in macrophages along with an impaired antigen presentation ability in circulating monocytes. Bacterial translocation supports—and is supported by—uncontrolled activation of immune cell responses and/or loss of toll-like receptor (TLR) tolerance, which can turn exaggerated inflammatory responses to systemic inflammation. Lipopolysaccharide (LPS) or endotoxin boosts systemic inflammatory activity through activation of TLR-2- and TLR-4-dependent pathways and facilitate a massive production of cytokines. This, in turn, results into elevated secretion of reactive oxygen species (ROS), which further enhances intestinal hyperpermeability and thus sustains a vicious circle of events widely known as “leaky gut.” Albumin can be of particular benefit in cirrhotic patients with spontaneous bacterial peritonitis and/or hepatorenal syndrome type of acute kidney injury (HRS-AKI) due to anti-inflammatory and antioxidative stress as well as volume-expanding properties and endothelial-stabilizing attributes. However, presence of autoantibodies against albumin in patients with liver cirrhosis has been described. Although previous research suggested that these antibodies should be regarded as naturally occurring antibodies (NOA), the origin of the antialbumin immune response is obscure. High occurrence of NAO/albumin complexes in patients with liver disease might reflect a limited clearance capacity due to bypassing portal circulation. Moreover, high burden of oxidized albumin is associated with less favorable outcome in patients with liver cirrhosis. To date, there is no data available as to whether oxidized forms of albumin result in neoepitopes recognized by the immune system. Nevertheless, it is reasonable to hypothesize that these alterations may have the potential to induce antialbumin immune responses and thus favor systemic inflammation.

scholarly journals Tranexamic acid modulates the immune response and reduces postsurgical infection rates

2019 ◽  
Vol 3 (10) ◽  
pp. 1598-1609 ◽  
Author(s):  
Dominik F. Draxler ◽  
Kah Yep ◽  
Gryselda Hanafi ◽  
Anoushka Winton ◽  
Maria Daglas ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Immune System ◽  
Tranexamic Acid ◽  
Postoperative Infection ◽  
Immune Cell ◽  
Innate Immune ◽  
Innate Immune Cell ◽  
Independent Effect ◽  
Surgical Trauma ◽  
Infection Rates

Abstract Tranexamic acid (TXA) is an antifibrinolytic agent that blocks plasmin formation. Because plasmin is known to promote inflammatory and immunosuppressive responses, we explored the possibility that plasmin-mediated immunosuppression in patients undergoing cardiac surgery can be directly reversed by TXA and decrease postoperative infection rates. The modulatory effect of TXA on inflammatory cytokine levels and on innate immune cell activation were evaluated with multiplex enzyme-linked immunosorbent assay and flow cytometry, respectively. Postoperative infection rates were determined in patients undergoing cardiac surgery and randomized to TXA (ACTRN12605000557639; http://www.anzca.edu.au). We demonstrate that TXA-mediated plasmin blockade modulates the immune system and reduces surgery-induced immunosuppression in patients following cardiac surgery. TXA enhanced the expression of immune-activating markers while reducing the expression of immunosuppressive markers on multiple myeloid and lymphoid cell populations in peripheral blood. TXA administration significantly reduced postoperative infection rates, despite the fact that patients were being administered prophylactic antibiotics. This effect was independent of the effect of TXA at reducing blood loss. TXA was also shown to exert an immune-modulatory effect in healthy volunteers, further supporting the fibrin-independent effect of TXA on immune function and indicating that baseline plasmin levels contribute to the regulation of the immune system in the absence of any comorbidity or surgical trauma. Finally, the capacity of TXA to reduce infection rates, modulate the innate immune cell profile, and generate an antifibrinolytic effect overall was markedly reduced in patients with diabetes, demonstrating for the first time that the diabetic condition renders patients partially refractory to TXA.

The 1000Plus study protocol – a prospective observational study on the mismatch concept in a 3.0 T MRI

2009 ◽  
Vol 36 (S 02) ◽  
Author(s):  
B Hotter ◽  
S Pittl ◽  
M Ebinger ◽  
G Oepen ◽  
K Jegzentis ◽  
...  
Keyword(s):  
Observational Study ◽  
Study Protocol ◽  
Prospective Observational Study ◽  
3.0 T ◽  
3.0 T Mri

scholarly journals Troponin Testing After Non-Cardiac Surgery in Ontario: An Observational Study

CJC Open ◽  
2021 ◽  
Author(s):  
Paymon M. Azizi ◽  
Duminda N. Wijeysundera ◽  
Harindra C. Wijeysundera ◽  
Peter C. Austin ◽  
Angela Jerath ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Observational Study

scholarly journals Neurological Complications of Cardiac Procedures

2021 ◽  
Author(s):  
Courtney M. Hrdlicka ◽  
Jeffrey Wang ◽  
Magdy Selim
Keyword(s):  
Cardiac Surgery ◽  
Cognitive Dysfunction ◽  
Postoperative Cognitive Dysfunction ◽  
Neurological Complications ◽  
Diagnostic Workup ◽  
Diagnosis And Management ◽  
Percutaneous Interventions ◽  
Cardiac Procedures ◽  
Appropriate Treatment ◽  
Periprocedural Stroke

AbstractNeurological complications after cardiac surgery and percutaneous cardiac interventions are not uncommon. These include periprocedural stroke, postoperative cognitive dysfunction after cardiac surgery, contrast-induced encephalopathy after percutaneous interventions, and seizures. In this article, we review the incidence, pathophysiology, diagnosis, and management of these complications. Improved understanding of these complications could lead to their prevention, faster detection, and facilitation of diagnostic workup and appropriate treatment.

Develop a Clinical Prediction Model for Postoperative Cognitive Dysfunction after Major Noncardiac Surgery in Elderly Patients: A Protocol for a Prospective Observational Study

Gerontology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Yang Shen ◽  
Xianchen Li ◽  
Junyan Yao
Keyword(s):  
Observational Study ◽  
Prediction Model ◽  
Cognitive Decline ◽  
Cognitive Dysfunction ◽  
Prospective Observational Study ◽  
Postoperative Cognitive Dysfunction ◽  
Noncardiac Surgery ◽  
Clinical Prediction ◽  
Clinical Prediction Model ◽  
Postoperative Cognitive Decline

Perioperative neurocognitive disorders (PNDs) refer to cognitive decline identified in the preoperative or postoperative period. It has been reported that the incidence of postoperative neurocognitive impairment after noncardiac surgery in patients older than 65 at 1 week was 25.8∼41.4%, and at 3 months 9.9∼12.7%. PNDs will last months or even develop to permanent dementia, leading to prolonged hospital stays, reduced quality of life, and increased mortality within 1 year. Despite the high incidence and poor prognosis of PNDs in the aged population, no effective clinical prediction model has been established to predict postoperative cognitive decline preoperatively. To develop a clinical prediction model for postoperative neurocognitive dysfunction, a prospective observational study (Clinical trial registration number: ChiCTR2000036304) will be performed in the Shanghai General Hospital during January 2021 to October 2022. A sample size of 675 patients aged &#x3e;65 years old, male or female, and scheduled for elective major noncardiac surgery will be recruited. A battery of neuropsychological tests will be used to test the cognitive function of patients at 1 week, 1 month, and 3 months postoperatively. We will evaluate the associations of PNDs with a bunch of candidate predictors including general characteristics of patients, blood biomarkers, indices associated with anesthesia and surgery, retinal nerve-fiber layer thickness, and frailty index to develop the clinical prediction model by using multiple logistic regression analysis and least absolute shrinkage and the selection operator (LASSO) method. The <i>k</i>-fold cross-validation method will be utilized to validate the clinical prediction model. In conclusion, this study was aimed to develop a clinical prediction model for postoperative cognitive dysfunction of old patients. It is anticipated that the knowledge gained from this study will facilitate clinical decision-making for anesthetists and surgeons managing the aged patients undergoing noncardiac surgery.

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