scholarly journals Proteins regulating cap-dependent translation are downregulated during total knee arthroplasty

2012 ◽  
Vol 302 (6) ◽  
pp. R702-R711 ◽  
Author(s):  
Stephen M. Ratchford ◽  
Ashley N. Bailey ◽  
Hilary A. Senesac ◽  
Austin D. Hocker ◽  
Keith Smolkowski ◽  
...  

Total knee arthroplasty (TKA) utilizes a tourniquet to reduce blood loss, maintain a clear surgical “bloodless” field, and to ensure proper bone-implant cementing. In 2007, over 600,000 TKAs were performed in the United States, and this number is projected to increase to 3.48 million procedures performed annually by 2030. The acute effects of tourniquet-induced ischemia-reperfusion (I/R) on human skeletal muscle cells are poorly understood and require critical investigation, as muscle atrophy following this surgery is rapid and represents the most significant clinical barrier to long-term normalization of physical function. To determine the acute effects of I/R on skeletal muscle cells, biopsies were obtained at baseline, maximal ischemia (prior to tourniquet release), and reperfusion (following tourniquet release). Quadriceps volume was determined before and 2 wk post-TKA by MRI. We measured a 36% decrease in phosphorylation of Akt Ser473during ischemia and 37% during reperfusion ( P < 0.05). 4E-BP1 Thr37/46phosphorylation decreased 29% during ischemia and 22% during reperfusion ( P < 0.05). eEF2 Thr56phosphorylation increased 25% during ischemia and 43% during reperfusion ( P < 0.05). Quadriceps volume decreased 12% in the TKA leg ( P < 0.05) and tended to decrease (6%) in the contralateral leg ( P = 0.1). These data suggest cap-dependent translation initiation, and elongation may be inhibited during and after TKA surgery. We propose that cap-dependent translational events occurring during surgery may precipitate postoperative changes in muscle cells that contribute to the etiology of muscle atrophy following TKA.

Author(s):  
Sean S. Rajaee ◽  
Eytan M. Debbi ◽  
Guy D. Paiement ◽  
Andrew I. Spitzer

AbstractGiven a national push toward bundled payment models, the purpose of this study was to examine the prevalence as well as the effect of smoking on early inpatient complications and cost following elective total knee arthroplasty (TKA) in the United States across multiple years. Using the nationwide inpatient sample, all primary elective TKA admissions were identified from 2012 to 2014. Patients were stratified by smoking status through a secondary diagnosis of “tobacco use disorder.” Patient characteristics as well as prevalence, costs, and incidence of complications were compared. There was a significant increase in the rate of smoking in TKA from 17.9% in 2012 to 19.2% in 2014 (p < 0.0001). The highest rate was seen in patients < 45 years of age (27.3%). Hospital resource usage was significantly higher for smokers, with a length of stay of 3.3 versus 2.9 days (p < 0.0001), and hospital costs of $16,752 versus $15,653 (p < 0.0001). A multivariable logistic model adjusting for age, gender, and comorbidities showed that smokers had an increased odds ratio for myocardial infarction (5.72), cardiac arrest (4.59), stroke (4.42), inpatient mortality (4.21), pneumonia (4.01), acute renal failure (2.95), deep vein thrombosis (2.74), urinary tract infection (2.43), transfusion (1.38) and sepsis (0.65) (all p < 0.0001). Smoking is common among patients undergoing elective TKA, and its prevalence continues to rise. Smoking is associated with higher hospital costs as well as higher rates of immediate inpatient complications. These findings are critical for risk stratification, improving of bundled payment models as well as patient education, and optimization prior to surgery to reduce costs and complications.


2009 ◽  
Vol 468 (1) ◽  
pp. 45-51 ◽  
Author(s):  
Kevin J. Bozic ◽  
Steven M. Kurtz ◽  
Edmund Lau ◽  
Kevin Ong ◽  
Vanessa Chiu ◽  
...  

2019 ◽  
Vol 127 (2) ◽  
pp. 531-545 ◽  
Author(s):  
Jonathan B. Muyskens ◽  
Douglas M. Foote ◽  
Nathan J. Bigot ◽  
Lisa A. Strycker ◽  
Keith Smolkowski ◽  
...  

The purpose of this study was to investigate the underlying cellular basis of muscle atrophy (Placebo) and atrophy reduction (essential amino acid supplementation, EAAs) in total knee arthroplasty (TKA) patients by examining satellite cells and other key histological markers of inflammation, recovery, and fibrosis. Forty-one subjects (53–76 yr) scheduled for TKA were randomized into two groups, ingesting 20 g of EAAs or placebo, twice-daily, for 7 days before TKA and for 6 wk after surgery. A first set of muscle biopsies was obtained from both legs before surgery in the operating room, and patients were randomly assigned and equally allocated to have two additional biopsies at either 1 or 2 wk after surgery. Biopsies were processed for gene expression and immunohistochemistry. Satellite cells were significantly higher in patients ingesting 20 g of essential amino acids twice daily for the 7 days leading up to surgery compared with Placebo (operative leg P = 0.03 for satellite cells/fiber and P = 0.05 for satellite cell proportions for Type I-associated cells and P = 0.05 for satellite cells/fiber for Type II-associated cells.) Myogenic regulatory factor gene expression was different between groups, with the Placebo Group having elevated MyoD expression at 1 wk and EAAs having elevated myogenin expression at 1 wk. M1 macrophages were more prevalent in Placebo than the EAAs Group. IL-6 and TNF-α transcripts were elevated postsurgery in both groups; however, TNF-α declined by 2 wk in the EAAs Group. EAAs starting 7 days before surgery increased satellite cells on the day of surgery and promoted a more favorable inflammatory environment postsurgery. NEW & NOTEWORTHY Clinical studies by our group indicate that the majority of muscle atrophy after total knee arthroplasty (TKA) in older adults occurs rapidly, within the first 2 wks. We have also shown that essential amino acid supplementation (EAAs) before and after TKA mitigates muscle atrophy; however, the mechanisms are unknown. These results suggest that satellite cell numbers are elevated with EAA ingestion before surgery, and after surgery, EAA ingestion positively influences markers of inflammation. Combined, these data may help inform further studies designed to address the accelerated sarcopenia that occurs in older adults after major surgery.


Author(s):  
Nequesha S. Mohamed ◽  
Wayne A. Wilkie ◽  
Ethan A. Remily ◽  
Iciar M. Dávila Castrodad ◽  
Mirlande Jean-Pierre ◽  
...  

AbstractIn the United States, one-third of adults are considered obese, and demand for total knee arthroplasty (TKA) is expected to rise in these patients. Surgeons are reluctant to operate on obese patients, but it is important to understand how obesity has affected TKA utilization. This study utilizes a national database to evaluate incidence, demographics, outcomes, charges, and cost in nonobese, overweight, nonmorbidly obese, and morbidly obese TKA patients. We queried the National Inpatient Sample from 2009 to 2016 for primary TKA patients identifying 4,053,037 nonobese patients, 40,077 overweight patients, 809,649 nonmorbidly obese patients, and 428,647 morbidly obese patients. Chi-square was used to analyze categorical variables, and one-way analysis of variance was used to analyze continuous variables. Nonmorbidly obese and morbidly obese patients represented 23.2% of all TKAs. TKA utilization increased 4.1% for nonobese patients, 121.6% for overweight patients, 73.6% for nonmorbidly obese patients, and 83.9% for morbidly obese patients. Morbidly obese patients were younger (p < 0.001), female (p < 0.001), Black (p < 0.001), poor (p < 0.001), and utilized private insurance (p < 0.001). They also had the longest length of stay (p < 0.001) and the highest mortality rate (p < 0.001). More morbidly obese patients were discharged to other facilities (p < 0.001), and they had the highest rate of complications (p < 0.001). Patients with morbid obesity had the highest charges (p < 0.001), but overweight patients had the highest costs (p < 0.001). The results of this study demonstrate the rise in obese and morbidly obese patients seeking TKAs, which may be reflection of the obesity epidemic in America. Although TKA utilization has increased for morbidly obese patients, this body mass index (BMI) category also has the highest rates of charges and complications, suggesting morbid obesity to be a modifiable risk factor leading to worse surgical and economic outcomes. Obese patients undergoing TKA may benefit from preoperative optimization of their weight, in an effort to reduce the risk of adverse outcomes.


2019 ◽  
Vol 5 (3) ◽  
pp. 94-101
Author(s):  
Yuki Kitsuda ◽  
Chika Tanimura ◽  
Kazuoki Inoue ◽  
Daeho Park ◽  
Mari Osaki ◽  
...  

2019 ◽  
Vol 33 (02) ◽  
pp. 100-105 ◽  
Author(s):  
Jesus M. Villa ◽  
Tejbir S. Pannu ◽  
Aldo M. Riesgo ◽  
Preetesh D. Patel ◽  
Michael A. Mont ◽  
...  

AbstractThe risk of surgical site infection in primary total knee arthroplasty (TKA) has been reduced with the use of prophylactic antibiotics. First or second generation cephalosporins are still recommended as the primary prophylactic choice, but with the rise in the incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections, evidence has emerged in favor of using dual antibiotics including vancomycin. However, it is unclear whether these combinations of antibiotic regimens further reduce postoperative infection rates. As a result, the objective of this review is to summarize the current literature concerning the use of dual prophylactic antibiotics in TKA. The most common dual prophylactic antibiotic combination is cefazolin (C) and vancomycin (V). In general, when comparing the effectiveness of single versus dual antibiotics, conflicting results have been reported. Three studies demonstrated no substantial decrease in overall postoperative infection rates with the use of dual antibiotics when compared with cefazolin alone. One found a significant decrease only in MRSA infection rates when using cefazolin and vancomycin (CV) (0.8% C alone vs. 0.08% CV, p < 0.05). Another investigation evaluated revision TKA patients who had combined cefazolin and vancomycin prophylaxis and showed a significant decline in both overall infection (7.89% [C] vs. 3.13% [CV]) and MRSA infection rates (4.21% [C] vs. 0.89% [CV]; p < 0.05). Concerning the safety profile of dual antibiotics, particular precautions must be adopted with the use of vancomycin because of the risk of acute kidney injury. Instead of vancomycin, an alternate less nephrotoxic antibiotic option might be teicoplanin. Unfortunately, this latter agent is only available outside of the United States. In conclusion, the value of dual antibiotic prophylaxis for the prevention of periprosthetic knee infections remains unclear primarily because all comparative studies performed between dual and single antibiotics have been of low evidence with retrospective designs. Larger multicenter randomized controlled trials are warranted.


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