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Endoplasmic Reticulum Stress Activation during Total Knee Arthroplasty.

ABSTRACT: Total knee arthroplasty (TKA) is the most common remediation for knee pain from osteoarthritis (OA) and is performed 650,000 annually in the U.S. A tourniquet is commonly used during TKA which causes ischemia and reperfusion (I/R) to the lower limb but the effects of I/R on muscle are not fully understood. Previous reports suggest upregulation of cell-stress and catabolism and downregulation of markers of cap-dependent translation during and after TKA. I/R has also been shown to cause endoplasmic reticulum (ER) stress and induce the unfolded protein response (UPR). We hypothesized that the UPR would be activated in response to ER stress during TKA. We obtained muscle biopsies from the vastus lateralis at baseline, before TKA; at maximal ischemia, prior to tourniquet deflation; and during reperfusion in the operating room. Phosphorylation of 4E-BP1 and AKT decreased during ischemia (-28%, p < .05; -20%, p < .05 respectively) along with an increase in eIF2α phosphorylation (64%, p < .05) suggesting decreased translation initiation. Cleaved ATF6 protein increased in ischemia (39%, p = .056) but returned to baseline during reperfusion. CASP3 activation increased during reperfusion compared to baseline (23%, p < .05). XBP1 splicing assays revealed an increase in spliced transcript during ischemia (31%, p < .05) which diminished during reperfusion. These results suggest that in response to I/R during TKA all three branches of the ER stress response are activated.

SUBMITTER: Hocker AD

PROVIDER: S-EPMC3804266 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Expression data from total knee arthroplasty patients

Project description:Ischaemic preconditioning is a method of protecting tissue against ischaemia-reperfusion injury. It is an innate protective mechanism that increases a tissue's tolerance to prolonged ischaemia when it is first subjected to short burst of ischaemia and reperfusion. It is thought to provide this protection by increasing the tissue's tolerance to ischaemia, therby reducing oxidative stress, inflammation and apoptosis in the preconditioned tissue. We used microarrays to investigate the genomic response induced by ischaemic preconditioning in muscle biopsies taken from the operative leg of total knee arthroplasty patients in order to gain insight into the ischaemic preconditioning mechanism. Patients undergoing primary knee arthroplasty were randomised to control and treatment (ischaemic preconditioning) groups. Patients in the treatment group received a preconditioning stimulus immediately prior to surgery. The ischaemic preconditioning stimulus consisted of three five-minute periods of tourniquet insufflation on the lower operative limb, interrupted by five minute periods of reperfusion. All patients had a tourniquet applied to the lower limb after the administration of spinal anaesthesia, as per normal protocol for knee arthroplasty surgery. Muscle biopsies were taken from the quadriceps muscle of the operative knee at the immediate onset of surgery (T0) and at 1 hour into surgery (T1). Total RNA was extracted from biospies of four control and four treatment patients and hybridised to the Affymetrix Human U133 2.0 chip.

2010-04-12 | E-GEOD-21164 | biostudies-arrayexpress

Expression data from total knee arthroplasty patients

2010-04-02 | GSE21164 | GEO

Popliteal artery damage during total knee arthroplasty.

Project description:Injury of popliteal artery during total knee arthroplasty is a relatively rare complication. We report on one case of transverse semi-dissection of the popliteal artery during the tibial cut and one case of popliteal pseudoaneurysm formation caused by Hohmann retractors. Diagnosis was made early in the first case but it was delayed in the second due to misdiagnosis of deep vein thrombosis. Both injuries were managed eventually by open surgery. Postoperative clinical examination and ultrasound imaging confirmed the successful restoration of the blood flow. This case report also describes the classification system of the type of vascular damage and describes the mechanism, the clinical presentation, diagnostic modalities and treatment options for these rare complications of total knee arthroplasty surgery.

| S-EPMC4956686 | biostudies-literature

Gait comparison of unicompartmental knee arthroplasty and total knee arthroplasty during level walking.

Project description:This meta-analysis compared the gait patterns of unicompartmental knee arthroplasty (UKA) patients and total knee arthroplasty (TKA) patients during level walking by evaluating the kinetics, kinematics, and spatiotemporal parameters. Studies were included in the meta-analysis if they assessed the vertical ground reaction force (GRF), joint moment at stance, flexion at initial contact, flexion at swing, overall range of motion (ROM), coronal knee angle at stance, walking speed, cadence, and stride length in UKA patients or TKA patients. Seven non-randomized studies met the criteria for inclusion in this meta-analysis. UKA patients and TKA patients were similar in terms of vertical GRF (95% CI: -0.36 to 0.20; P = 0.60), joint moment (95% CI: -0.55 to 0.63; P = 0.90), kinematic outcomes (95% CI: -0.72 to 1.02; P = 0.74), walking speed (95% CI: -0.27 to 0.81; P = 0.32), and cadence (95% CI: -0.14 to 0.68; P = 0.20). In contrast, the stride length (95% CI: 0.01 to 0.80; P = 0.04) differed significantly between groups. Subgroup analyses revealed that the pooled data were similar between the groups: 1st maximum (heel strike), -0.18 BW (P = 0.53); 1st minimum (mid-stance), -0.43 BW (P = 0.08); and 2nd maximum (toe off), -0.03 BW (P = 0.87). On gait analysis, there were no significant differences in vertical GRF, joint moment at stance, overall kinematics, walking speed, or cadence between UKA patients and TKA patients during level walking. However, the TKA group had significantly shorter stride length than UKA patients. Although the comparison was inconclusive in determining which types of knee arthroplasty offered the closest approximation to normal gait, we consider it important to provide better rehabilitation programs to reduce the abnormal stride length in TKA patients compared to UKA patients.

| S-EPMC6117028 | biostudies-literature

Robotic Total Knee Arthroplasty vs Conventional Total Knee Arthroplasty: A Nationwide Database Study.

Project description:BackgroundAs robot-assisted equipment is continuously being used in orthopaedic surgery, the past few decades have seen an increase in the usage of robotics for total knee arthroplasty (TKA). Thus, the purpose of the present study is to investigate the differences between robotic TKA and nonrobotic TKA on perioperative and postoperative complications and opioid consumption.MethodsAn administrative database was queried from 2010 to Q2 of 2017 for primary TKAs performed via robot-assisted surgery vs non-robot-assisted surgery. Systemic and joint complications and average morphine milligram equivalents were collected and compared with statistical analysis.ResultsPatients in the nonrobotic TKA cohort had higher levels of prosthetic revision at 1-year after discharge (P < .05) and higher levels of manipulation under anesthesia at 90 days and 1-year after discharge (P < .05). Furthermore, those in the nonrobotic TKA cohort had increased occurrences of deep vein thrombosis, altered mental status, pulmonary embolism, anemia, acute renal failure, cerebrovascular event, pneumonia, respiratory failure, and urinary tract infection during the inpatient hospital stay (all P < .05) and at 90 days after discharge (all P < .05). All of these categories remained statistically increased at the 90-days postdischarge date, except pneumonia and stroke. Patients in the nonrobotic TKA cohort had higher levels of average morphine milligram equivalents consumption at all time periods measured (P < .001).ConclusionsIn the present study, the use of robotics for TKA found lower revision rates, lower incidences of manipulation under anesthesia, decreased occurrence of systemic complications, and lower opiate consumption for postoperative pain management. Future studies should look to further examine the long-term outcomes for patients undergoing robot-assisted TKA.Level of evidenceLevel III.

| S-EPMC7772451 | biostudies-literature

Adolescent total knee arthroplasty.

Project description:BackgroundManagement of adolescent patients with end-stage arthritis is challenging. Nonoperative treatments may be ineffective and total knee arthroplasty (TKA) is rarely performed. Currently, minimal long-term data are available on the outcomes in this patient population. Our goal was to describe TKA for patients with end-stage arthritis who were aged 20 years and younger.MethodsThe Joint Registry at our institution was used to identify 19 patients (29 TKAs) aged 20 years and younger that underwent a primary TKA. The average age was 18 years (range 14-20 years) and follow-up was 14.5 years (range: 2.1-25.5 years).ResultsThe preoperative diagnoses were juvenile idiopathic arthritis (n = 19), avascular necrosis (n = 4), sepsis (n = 2), trauma (n = 2), dysplasia (n = 1), and hemophilia (n = 1). There was a decrease in the number of TKAs performed for inflammatory arthritis over the last several decades. Implant survivorship at 5 and 10 years was 96% and 94%, respectively.ConclusionsWe identified a 95% 10-year implant survivorship utilizing standard TKA components in pediatric patients. Performing a TKA in adolescent patients has long-term potential risks including infection and bone loss but may provide pain relief and good long-term results and should be used with caution.

| S-EPMC5484984 | biostudies-literature

Muscle transcriptome analysis following Total Knee Arthroplasty with Tourniquet

Project description:Transcriptome profiling was performed on muscle biopsies from patients immediately before Total Knee Arthroplasty and two hours after TKA and tourniquet application.

2016-02-01 | GSE75432 | GEO

Compromised knee internal rotation in total knee arthroplasty patients during stair climbing.

Project description:Due to the significant role of rotational properties for normal knee function, this study aimed to investigate transverse plane kinematics and kinetics in total knee arthroplasty and unicondylar knee arthroplasty patients during activities of daily living compared to a healthy control group, including stair ascent and descent. The study participants consisted of a total knee arthroplasty group including posterior cruciate retaining and posterior stabilized designs as well as a unicondylar knee arthroplasty group and a healthy control group. Three-dimensional kinematics and kinetics were captured using a Vicon system and two Kistler force plates embedded in the floor and another two in a staircase. Inverse dynamics of the lower limbs was computed in Anybody™ Modeling System. Transverse plane joint angles and joint moments were analyzed utilizing the statistical non-parametric mapping approach, considering the entire curve shape for statistical analysis. The patients with total knee arthroplasty exhibited significantly reduced knee internal rotation of the operated knee compared to the control group and the patients' unimpaired limb, especially during the stair climbing tasks. Both unicondylar and total knee arthroplasty patients were found to have similar reduced internal rotation motion time series in stair descent. In conclusion, potential kinematic and kinetic benefits of unicondylar knee arthroplasty over total knee arthroplasty could not be proven in the current study. Aside from the usually mentioned reasons inducing constrained knee internal rotation in total knee arthroplasty patients, future studies should investigate to what extent co-contraction may contribute to this functional impairment in patients after knee arthroplasty surgery.

| S-EPMC6179266 | biostudies-literature

Activation of endoplasmic reticulum stress response during the development of ischemic heart disease.

Project description:Endoplasmic reticulum (ER) stress has been found to be associated with neurodegenerative diseases and diabetes mellitus. Whether ER stress is involved in the development of heart disease is not known. Cardiac-specific expression of monocyte chemoattractant protein-1 (MCP-1) in mice causes the development of ischemic heart disease. Here we report that microarray analysis of gene expression changes in the heart of these transgenic mice revealed that a cluster of ER stress-related genes was transcriptionally activated in the heart during the development of ischemic heart disease. The gene array results were verified by quantitative real-time PCR that showed highly elevated transcript levels of genes involved in unfolded protein response such as ER and cytoplasmic chaperones, oxidoreductases, protein disulfide isomerase (PDI) family, and ER-associated degradation system such as ubiquitin. Immunoblot analysis confirmed the expression of chaperones, PDI, and ubiquitin. Immunohistochemical analyses showed that ER stress proteins were associated mainly with the degenerating cardiomyocytes. A novel ubiquitin fold modifier (Ufm1) that has not been previously associated with ER stress and not found to be induced under any condition was also found to be upregulated in the hearts of MCP mice (transgenic mice that express MCP-1 specifically in the heart). The present results strongly suggest that activation of ER stress response is involved in the development of ischemic heart disease in this murine model.

| S-EPMC1575464 | biostudies-literature

Gout After Total Knee Arthroplasty.

Project description:Crystalline arthropathies are well-known pathologies in a native knee; however, the literature is scarce with regards to crystalline arthropathies in a total knee arthroplasty (TKA). The presentation of crystalline arthropathy in a TKA can be similar to a periprosthetic joint infection (PJI), making it difficult to distinguish between the 2 diagnoses. We present 1 case highlighting the similarity between crystalline arthropathy and PJI. A 71-year-old man with a history of bilateral TKAs presented with bilateral painful knee effusions and was initially presumed to have PJIs; however, he was later diagnosed with gout and successfully treated medically. A complete review of the literature demonstrates that crystalline arthropathies after TKA are infrequently reported and can be difficult to decipher from PJIs, and there is a lack of standardized treatment.

| S-EPMC7303497 | biostudies-literature

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