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BACKGROUND. The kynurenine pathway (KP) has been identified as a potential mediator linking acute illness to cognitive dysfunction by generating neuroactive metabolites in response to inflammation. Delirium (acute confusion) is a common complication of acute illness and is associated with increased risk of dementia and mortality. However, the molecular mechanisms underlying delirium, particularly in relation to the KP, remain elusive. METHODS. We undertook a multicenter observational study with 586 hospitalized patients (248 with delirium) and investigated associations between delirium and KP metabolites measured in cerebrospinal fluid (CSF) and serum by targeted metabolomics. We also explored associations between KP metabolites and markers of neuronal damage and 1-year mortality. RESULTS. In delirium, we found concentrations of the neurotoxic metabolite quinolinic acid in CSF (CSF-QA) (OR 2.26 [1.78, 2.87], P < 0.001) to be increased and also found increases in several other KP metabolites in serum and CSF. In addition, CSF-QA was associated with the neuronal damage marker neurofilament light chain (NfL) (p 0.43, P < 0.001) and was a strong predictor of 1-year mortality (HR 4.35 [2.93, 6.45] for CSF-QA > 100 nmol/L, P < 0.001). The associations between CSF-QA and delirium, neuronal damage, and mortality remained highly significant following adjustment for confounders and multiple comparisons. CONCLUSION. Our data identified how systemic inflammation, neurotoxicity, and delirium are strongly linked via the KP and should inform future delirium prevention and treatment clinical trials that target enzymes of the KP. FUNDING. Norwegian Health Association and South-Eastern Norway Regional Health Authorities., Introduction The kynurenine pathway (KP) has been identified as a potential mediator linking acute illness to cognitive dysfunction by generating neuroactive metabolites in response to inflammation (1, 2). An imbalance [...]

Alterations in brain energy metabolism have long been proposed as one of several neurobiological processes contributing to delirium. This is supported by previous findings of altered CSF lactate and neuron-specific enolase concentrations and decreased glucose uptake on brain-PET in patients with delirium. Despite this, there are limited data on metabolic alterations found in CSF samples, and targeted metabolic profiling of CSF metabolites involved in energy metabolism has not been performed. The aim of the study was to investigate whether metabolites related to energy metabolism in the serum and CSF of patients with hip fracture are associated with delirium. The study cohort included 406 patients with a mean age of 81 years (standard deviation 10 years), acutely admitted to hospital for surgical repair of a hip fracture. Delirium was assessed daily until the fifth postoperative day. CSF was collected from all 406 participants at the onset of spinal anaesthesia, and serum samples were drawn concurrently from 213 participants. Glucose and lactate in CSF were measured using amperometry, whereas plasma glucose was measured in the clinical laboratory using enzymatic photometry. Serum and CSF concentrations of the branched-chain amino acids, 3-hydroxyisobutyric acid, acetoacetate and β-hydroxybutyrate were measured using gas chromatography-tandem mass spectrometry (GC-MS/MS). In total, 224 (55%) patients developed delirium pre- or postoperatively. Ketone body concentrations (acetoacetate, β-hydroxybutyrate) and branched-chain amino acids were significantly elevated in the CSF but not in serum among patients with delirium, despite no group differences in glucose concentrations. The level of 3-hydroxyisobutyric acid was significantly elevated in both CSF and serum. An elevation of CSF lactate during delirium was explained by age and comorbidity. Our data suggest that altered glucose utilization and a shift to ketone body metabolism occurs in the brain during delirium. [ABSTRACT FROM AUTHOR]

Introduction Cartilage wear is a concern after hemiarthroplasty. The precise pattern of the progression of wear has not been evaluated. We previously reported the application of radiostereonetric analysis (RSA) for the measurement of cartilage wear in patients. The purpose of this study was to report the amount and the orientation of the steady state wear of cartilage between 1 and 3 years after bipolar hemiarthroplasty. Methods 22 patients with a bipolar hemiarthroplasty for displaced femoral neck fracture were included. 10 patients completed the mean follow up of 37 months. The cartilage wear was evaluated by calculating the migration of the bipolar head in reference to the markers in the acetabulum using RSA. Results The mean age of the patients at the final follow-up was 80 (range 67-91) years. The 3-D migration was -0.02 mm (SD 0.30) between 1 and 3 years. The migration in each direction was 0.03 mm (SD 0.49) in medial, 0.03 mm (SD 0.14) in proximal and 0.11 mm (SD 0.29) in posterior directions. 2 patients showed migration of more than 0.2 mm. The large initial migration seen in some patients up to 1 year did not progress further. Total wear after 37 months was 0.43 mm (SD 0.17). Conclusions Cartilage wear progressed slowly in 2 of 10 patients from 1 to 3 years. No pelvic penetration was seen. We believe that RSA will give a basic knowledge about the development and the progression of cartilage wear after hemiarthroplasty. [ABSTRACT FROM AUTHOR]

Background and purpose - Registry-based studies have reported an increased risk of aseptic tibial loosening for the cemented Low Contact Stress (LCS) total knee replacement compared with other cemented designs; however, the reasons for this have not been established. We made a retrieval analysis with the aim of identifying the failure mechanism. Patients and methods - We collected implants, cement, tissue, blood, and radiographs from 32 failed LCS Complete cases. Damage to the tibial baseplate and insert was assessed. Exposure to wear products was quantified in 11 cases through analysis of periprosthetic tissue and blood. Implant alignment and bone cement thickness was compared with a control group of 43 nonrevised cases. Results - Loosening of the tibial baseplate was the reason for revision in 25 retrievals, occurring at the implant-cement interface in 16 cases. Polishing was observed on the lower surface of the baseplate and correlated to the level of cobalt, chromium, and zirconium in the blood. No evidence of abnormally high polyethylene wear was present. For each 1 mm increase in cement thickness the odds of failure due to aseptic loosening decreased by 61%. Greater varus alignment was associated with a shorter time to failure. The roughness, Ra, of a new LCS baseplate's lower surface was 3.7 (SD 0.7) µm. Interpretation - Debonding of the tibial component at the implant-cement interface was the predominant cause of tibial aseptic loosening. A thin cement layer may partly explain the poor performance. Furthermore, the comparatively low tibial surface roughness and the lack of a keeled stem may have played a role in the failures observed. [ABSTRACT FROM AUTHOR]

Cartilage wear is a concern after hemiarthroplasty. The precise pattern of the progression of wear has not been evaluated. We previously reported the application of radiostereonetric analysis (RSA) for the measurement of cartilage wear in patients. The purpose of this study was to report the amount and the orientation of the steady state wear of cartilage between 1 and 3 years after bipolar hemiarthroplasty.~Introduction~Background~22 patients with a bipolar hemiarthroplasty for displaced femoral neck fracture were included. 10 patients completed the mean follow up of 37 months. The cartilage wear was evaluated by calculating the migration of the bipolar head in reference to the markers in the acetabulum using RSA.~Methods~Methods~The mean age of the patients at the final follow-up was 80 (range 67-91) years. The 3-D migration was -0.02 mm (SD 0.30) between 1 and 3 years. The migration in each direction was 0.03 mm (SD 0.49) in medial, 0.03 mm (SD 0.14) in proximal and 0.11 mm (SD 0.29) in posterior directions. 2 patients showed migration of more than 0.2 mm. The large initial migration seen in some patients up to 1 year did not progress further. Total wear after 37 months was 0.43 mm (SD 0.17).~Results~Results~Cartilage wear progressed slowly in 2 of 10 patients from 1 to 3 years. No pelvic penetration was seen. We believe that RSA will give a basic knowledge about the development and the progression of cartilage wear after hemiarthroplasty.~Conclusions~Conclusions [ABSTRACT FROM AUTHOR]