Preoperative Emergency Department Visits Are Predictive of 90-Day Postoperative Emergency Department Visits and Discharge Disposition in Total Knee Arthroplasty Patients.

The increasing number of patients undergoing total knee arthroplasty (TKA) has resulted in efforts to better understand patient utilization of healthcare services in the 90-day postoperative period. The primary purpose of this study was to examine whether emergency department (ED) visits in the year prior to elective TKA were predictive of postoperative ED visits in the 90-day global period following surgery. A retrospective chart review was performed for all patients undergoing TKA from June 1, 2011 to December 31, 2015 at a Veterans Affairs hospital. Total number of ED visits in the year prior to surgery and 90 days following surgery were tabulated. Binary and ordinal logistic regression analyses were utilized to determine if preoperative ED visits were predictive of postoperative ED visits. The significance level was set to α = 0.05. Overall, 611 eligible TKA procedures were performed. The logistic regression model for postoperative ED visits was significant (p < 0.001), with the number of preoperative ED visits (1 vs. 0: p < 0.001; 2 vs. 1: p = 0.012) and presence of diabetes (p = 0.007) both predicting the likelihood of a postoperative ED visit. Healthcare changes that are redefining the concept of quality of care to include the postoperative care episode, coupled with an increasingly aging population in need of TKA, will continue to challenge orthopaedic surgeons to provide safe, competent, and cost-effective care to patients. The results of this study demonstrate that a patient's propensity to visit the ED prior to TKA is predictive of a tendency to do so postoperatively and is of use to surgeons when evaluating and counselling patients who will be undergoing a TKA.

Biomechanical Comparison of Tape Versus Suture in Simulated Achilles Tendon Midsubstance Rupture.

As sutures have progressed in strength, increasing evidence supports the suture tendon interface as the site where most tendon repairs fail. We hypothesized that suture tape would have a higher load to failure versus polyblend suture due to its larger surface area. Eleven matched pairs of cadaveric Achilles tendons were sutured with 2 mm wide braided ultrahigh molecular weight polyethylene tape (Tape) or 2 mm wide braided ultrahigh molecular weight polyethylene suture (Suture) using a Krackow repair method. All Achilles repair constructs were cyclically loaded, after which they were loaded to failure. Change in suture footprint height, clinical and ultimate load to failure, and location of failure was recorded. Clinical loads to failure for Tape and Suture were 290.4 ± 74.8 and 231.7 ± 70.4 Newtons, respectively (p= .01). Ultimate loads to failure for Tape and Suture were 352.9 ± 108.1 and 289.8 ± 53.7 Newtons, respectively (p = .11). Cyclic testing resulted in significant changes in footprint height for both Tape and Suture, but the 2 sutures did not differ in terms of the magnitude of change in footprint height (p = .52). The suture tendon interface was the most common site of failure for both Tape and Suture. Our results suggest that Tape may provide added repair strength in vivo for Achilles midsubstance rupture.

Multimodal Pain Management With Adductor Canal Block Decreases Opioid Consumption Following Total Knee Arthroplasty.

BACKGROUND: Ease of access to opioids in the perioperative period is a risk factor for subsequent opioid misuse. The purpose of this study was to quantify a decrease in opioid consumption following implementation of a new analgesic protocol after total knee arthroplasty (TKA). METHODS: A retrospective cohort study was performed analyzing patients who underwent TKA at a US Department of Veterans Affairs medical center. Patients were divided into 2 groups by multimodal analgesic regimen: Analgesia with intraoperative general anesthesia, a patient-controlled analgesia pump, and oral opioids (control group) or analgesia with intraoperative spinal anesthesia, a multimodal medication regimen, and an adductor canal block (protocol group). RESULTS: A total of 533 TKAs were included. The mean (SD) IV morphine equivalent dose (MED) requirement was 178.2 (98.0) for the control and 12.0 (24.6) for the protocol group (P < .001). Total mean (SD) opioid MED requirement was 241.7 (120.1) for the control group and 74.8 (42.7) for the protocol group (P < .001). The protocol group required only 6.7% of the IV opioids and the control group 30.9%. No difference in oral opioid requirements was found (P = .85). The control group required more opioid refills at the first postoperative visit (P < .001). CONCLUSIONS: The described analgesic protocol resulted in significant decreases in IV and total opioid requirement, and lower rates of opioid prescriptions at the first postoperative visit. These findings demonstrate a decrease in opioid utilization with modern perioperative analgesia protocols and reinforce multiple recommendations to decrease opioid exposure and access.

SGA scores have poor correlation with serum albumin in obese hemodialysis patients: a secondary analysis.

OBJECTIVE: The objective of this study was to determine the relationship between serum albumin and the Subjective Global Assessment (SGA) in a sample of obese hemodialysis (HD) patients. DESIGN AND METHOD: Study subjects (N = 253) included patients who were categorized into well-nourished (68%, SGA score 6-7) and malnourished (score 1-5) groups, and, on the basis of the body mass index (BMI), into obese (BMI > 30 kg/m(2); 35%) and nonobese (BMI < 30 kg/m(2)). The mean baseline data (±standard deviation) were as follows: age, 63.5 ± 14.3 years; BMI, 29 ± 8 kg/m(2); and serum albumin, 3.8 ± 0.4 mg/dL (bromocresol green). The secondary analysis of data from the SGA Validation Project and Nutrition Algorithm Preliminary Report determined the relationship between the 7-point SGA and serum albumin concentrations in a sample of obese HD patients. Data were analyzed at Case Western Reserve University from a total of 253 HD patients. MAIN OUTCOME MEASURE: The SGA scores in the BMI groups were compared with serum albumin as an objective measure of nutrition and inflammation risk. RESULTS: By using analysis of variance, the obese and nonobese populations showed statistically significant differences in SGA scores (obese: P < .3468, nonobese: P < .0080) and serum albumin values (obese, P < .0943; nonobese, P < .0183) between well-nourished and malnourished groups. A multivariable nominal logistic fit was used to predict SGA group with age and gender as covariates. Serum albumin values (P < .0057) and BMI values greater than 30 (P < .0090) predicted SGA group. CONCLUSION: The secondary analysis showed that SGA does not correlate well with serum albumin; thus, it may not be a valid nutrition assessment tool among obese HD patients.

Optimization of alpha-ketoamide based p38 inhibitors through modifications to the region that binds to the allosteric site.

We have optimized a novel series of potent p38 MAP kinase inhibitors based on an alpha-ketoamide scaffold through structure based design that due to their extended molecular architecture bind, in addition to the ATP site, to an allosteric pocket. In vitro ADME, in vivo PK and efficacy studies show these compounds to have drug-like characteristics and have resulted in the nomination of a development candidate which is currently in phase II clinical trials for the oral treatment of inflammatory conditions.

KR-003048, a potent, orally active inhibitor of p38 mitogen-activated protein kinase.

The tumor necrosis factor-alpha (TNF-alpha) cytokine, secreted by activated monocytes/macrophages and T lymphocytes, is implicated in several diseases, including rheumatoid arthritis, chronic obstructive pulmonary disease, inflammatory bowel disease, and osteoporosis. Monocyte/macrophage production of TNF-alpha is largely driven by p38alpha mitogen-activated protein kinase (MAP kinase), an intracellular soluble serine-threonine kinase. p38alpha MAP kinase is activated by growth factors, cellular stresses, and cytokines such as TNF-alpha and interleukin-l (IL-I). The primary contribution of p38alpha activation to excess TNF-alpha in settings of both chronic and acute inflammation has instigated efforts to find inhibitors of this enzyme as possible therapies for associated disease states. Analogue design, synthesis, and structure-activity studies led to the identification of 5-tert-butyl-N-cyclopropyl-2-methoxy-3-{2-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-2-oxo-acetylamino}-benzamide (KR-003048) as a potent inhibitor of the p38 MAP kinase signaling pathway in vitro and in vivo. The inhibition in vitro of human p38alpha enzyme activity and lipopolysaccharide (LPS)-induced p38 activation and subsequent TNF-alpha release is described. KR-00348 was demonstrated to be a potent inhibitor of inflammatory cytokine production ex vivo in rat and human whole blood, and showed good oral bioavailability. Additionally, efficacy in mouse and rat models of acute and chronic inflammation was obtained. KR-003048 possessed therapeutic activity in acute models, demonstrating substantial inhibition of carrageenan-induced paw edema and in vivo LPS-induced TNF release at 30mg/kg p.o. Collagen-induced arthritis in mice was significantly inhibited by 10 and 30mg/kg doses of KR-003048. Evidence for disease-modifying activity in this model was indicated by histological evaluation of joints.

'Reverse' alpha-ketoamide-based p38 MAP kinase inhibitors.

We have identified a second series of potent p38 inhibitors. As with our first generation series, these compounds are based on an alpha-ketoamide scaffold. The reversal of the ketoamide order, however, introduces more chemical flexibility and in addition results in improve potencies against p38.

The design and synthesis of novel alpha-ketoamide-based p38 MAP kinase inhibitors.

We have identified a novel series of potent p38 MAP kinase inhibitors through structure-based design which due to their extended molecular architecture bind, in addition to the ATP site, to an allosteric pocket. In vitro ADME and in vivo PK studies show these compounds to have drug-like characteristics which could result in the development of an oral treatment for inflammatory conditions.