Age-Related Decline in Patient-Reported Outcomes 2 and 5 Years Following Total Hip Arthroplasty.

BACKGROUND: Patient-reported outcome measures (PROMs) help assess therapeutic effectiveness. This study assessed the effect of advanced age on the Hip Disability and Osteoarthritis Outcome Score (HOOS) and Lower Extremity Activity Scale (LEAS) after total hip arthroplasty (THA). METHODS: A prospective cohort of patients underwent primary THA at our institution between May 2007 and December 2011. Exposure was age at the time of surgery and outcomes were HOOS and LEAS scores 2 and 5 years postsurgery. We used a multivariable longitudinal generalized estimating equation to elucidate the effect of age on PROM scores. RESULTS: Our analysis of 3700 THA patients (mean age, 66 years; 56.4% female) demonstrated a decline in scores by age for the LEAS, HOOS Activities of Daily Living, and HOOS Sport and Recreation domains. There was also association between age and HOOS Symptoms and HOOS Quality of Life domains, but not between age and the HOOS Pain domain. Critical ages at which the relationship between age and outcome changed was 63 years for the HOOS Pain, Symptom, Activities of Daily Living, and Quality of Life domains, and 72 years for the HOOS Sport and Recreation domain and the LEAS. CONCLUSION: Patients undergoing THA at older ages reported lower activity and sports and recreation scores than younger patients, but similar pain, symptoms, and quality of life scores. This knowledge can help physicians guide patients' expectations before THA. Our findings also indicate that PROM scores should be age adjusted when used for quality or value comparisons between hospitals or physicians.

Age-Related Functional Decline Following Total Knee Arthroplasty: Risk Adjustment is Mandatory.

BACKGROUND: Patient-reported outcome measures (PROMs) are being used increasingly to determine the success of total knee arthroplasty (TKA). Our goal is to investigate whether advanced age is associated with lower PROM scores. METHODS: We used our hospital's TKA registry to examine the relationship between age and PROMs in all patients 50-90 years of age who underwent unilateral or simultaneous bilateral primary TKA between 2007 and 2011 with a primary diagnosis of osteoarthritis. All 5 domains of the Knee Injury and Arthritis Outcomes Score (KOOS) and the Lower Extremity Activity Scale (LEAS) at baseline, 2 years, and 5 years were collected. The association between age and PROM score was assessed by piecewise linear regression using generalized estimating equations, adjusting for demographics, comorbidity, and baseline score. RESULTS: Significant nonlinear relationships among age, KOOS subdomains, and LEAS were found. The placement of the age spline knot was at 70 years for KOOS Symptom and 68 years for KOOS Pain, KOOS Activities of Daily Living (ADL), and LEAS. The KOOS Symptom domain showed a significant worsening between 2-year and 5-year follow-up (P < .05) as patients got older. CONCLUSION: We found an age-related decline in KOOS Pain, KOOS Symptom, KOOS ADL, and LEAS scores. The best fitting spline knots were at 68 (KOOS Pain, KOOS ADL, and LEAS) and 70 years (KOOS Symptoms), respectively. This demonstrates that there is a critical age at which functional decline begins regardless of the quality of the TKA surgery. Our findings will help surgeons accurately guide patient expectations after TKA based on age. LEVEL OF EVIDENCE: Level II, prognostic study.

Failure After Modern Total Knee Arthroplasty: A Prospective Study of 18,065 Knees.

BACKGROUND: We sought is to determine the mechanism of failure among primary total knee arthroplasties (TKAs) performed at a single high-volume institution by asking the following research questions: (1) What are the most common failure modes for modern TKA designs? and (2) What are the preoperative risk factors for failure following primary TKA? METHODS: From May 2007 to December 2012, 18,065 primary TKAs performed on 16,083 patients at a single institution were recorded in a prospective total joint arthroplasty registry with a minimum of 5-year follow-up. We retrospectively reviewed patient charts to determine a cause of failure for primary TKAs. A cox proportional hazard model was used to determine the risk of revision surgery following primary TKA. RESULTS: The most common reasons for failure within 2 years after TKA were infection and stiffness. The multivariable regression identified the following preoperative risk factors for TKA failure: history of drug abuse (hazard ratio [HR] 4.68; P = 0.03), deformity/mechanical preoperative diagnosis (HR 3.52; P < .01), having a constrained condylar knee implant over posterior-stabilized implant (HR 1.99; P < .01), post-traumatic/trauma preoperative diagnosis (HR 1.78; P = .03), and younger age (HR 0.61; P < .01) CONCLUSION: These findings add to the growing data that primary TKAs are no longer failing from polyethylene wear-related issues. This study identified preoperative risk factors for failure of primary TKAs, which may be useful information for developing strategies to improve outcomes following TKA.

Intravenous administration of tranexamic acid effectively reduces blood loss in primary total knee arthroplasty in a 610-patient consecutive case series.

BACKGROUND: Tranexamic acid (TXA) has been reported to demonstrate efficacy in reducing blood loss during arthroplasty procedures. STUDY DESIGN AND METHODS: This study examines the effectiveness of TXA as a central element of a patient blood management program (PBMP) by evaluating blood loss and transfusion of red blood cells in three consecutive groups of patients undergoing routine total knee arthroplasty (TKA). Approximately 200 patients were in each group as follows: Group 1 was a control without TXA, Group 2 was intraarticular administration, and Group 3 was intravenous (IV) administration. RESULTS: The IV group demonstrated a small but significant lower blood loss compared to the two other groups measured by hemoglobin (Hb) drift and nadir Hb levels. The routine use of TXA along with the other aspects of our PBMP provided significant cost savings due to the reduction in transfusions as well as a decrease in length of stay and has been an important element of our successful implementation of a PBMP. CONCLUSION: This study demonstrates a significant benefit from the routine use of TXA for total knee arthroplasty and is one of the first studies to demonstrate a small but significant benefit for IV administration in comparison to intraarticular administration. The routine use of TXA as a central element of a PBMP provides a cost savings and can help reduce the rate of transfusions for total knee arthroplasty.

Hip arthroplasty for osteonecrosis of the femoral head secondary to alcohol abuse.

Although the challenges of hip arthroplasty for avascular necrosis (AVN) are known, limited data exist to describe patient demographics and outcomes in the setting of AVN attributed to alcoholism. We retrospectively identified 43 patients (62 hips) who underwent primary hip arthroplasty between 1999 and 2016 for a diagnosis of AVN of the femoral head with a concomitant diagnosis of alcohol abuse and minimum follow-up of 2 years (mean, 8.6 years). The mean age was 51 years, predominantly male (88%), with a high rate of comorbidities. History of cigarette smoking was prevalent (65%). Mean length of stay was 5.3 days, which is prolonged due to a high prevalence of acute postoperative alcohol withdrawal (14.5% of cases). There were 5 early (≤2 years) reoperations (8% of hips) for instability, periprosthetic acetabular fracture and component loosening, heterotopic ossification, superficial infection, and acute periprosthetic infection. There were no additional radiographic failures. The mean postoperative Hip dysfunction and Osteoarthritis Outcome Score for Joint Replacement was 97.8 ± 7.8, indicative of excellent outcomes at final follow-up of 2 to 18 years. Early risks associated with hip replacement surgery must be communicated to the predominantly young male subgroup of patients with AVN attributed to alcoholism, but these patients may achieve excellent mid- to long-term outcomes.

Minimal Increase in Total Hip Arthroplasty Surgical Procedural Time with the Use of a Novel Surgical Navigation Tool.

BACKGROUND: Computer-assisted navigation has proven effective at improving the accuracy of component placement during Total Hip Arthroplasty (THA); however, the material costs, line-of-site issues and potential for significant time increases have limited their widespread use. OBJECTIVE: The purpose of this study was to investigate the impact of an imageless navigation device on surgical time, when compared with standard mechanical guides. METHODS: We retrospectively reviewed prospectively collected data from 61 consecutive primary unilateral THA cases (posterior approach) performed by a single surgeon. Procedural time (incision to closure) for THA performed with (intervention) or without (control) a computer-assisted navigation system was compared. In the intervention group, the additional time associated with the use of the device was recorded. Mean times were compared using independent samples t-tests with statistical significance set a priori at p<0.05. RESULTS: There was no statistically significant difference between procedural time in the intervention and control groups (102.3±28.3 mins vs. 99.1±14.7 mins, p=0.60). The installation and use of the navigation device accounted for an average of 2.9 mins (SD: 1.6) per procedure, of which device-related setup performed prior to skin incision accounted for 1.1 mins (SD: 1.1) and intra-operative tasks accounted for 1.6 mins (SD: 1.2). CONCLUSION: In this series of 61 consecutive THAs performed by a single surgeon, the set-up and hands-on utilization of a novel surgical navigation tool required an additional 2.9 minutes per case. We suggest that the intraoperative benefits of this novel computer-assisted navigation platform outweigh the minimal operative time spent using this technology.

Lumbar chance fracture after direct anterior total hip arthroplasty.

This report describes a patient with ankylosing spondylitis (AS) who underwent total hip arthroplasty (THA) by the direct anterior approach and sustained a L4-5 extension fracture dislocation with neural deficits. A magnetic resonance imaging revealed an epidural hematoma at the site of the fracture causing critical stenosis. The patient was taken to the operating room for a L3-S1 posterior decompression with L2-pelvis posterior spinal fusion. AS and diffuse idiopathic skeletal hyperostosis create a stiff spine that predisposes to fractures because of the larger moment arms experienced than normal spines. The arthroplasty surgeon performing THA should be aware and take precautions to reduce stress on the spine.

Arthroscopic Management of Osteoarthritis.

Arthroscopic surgery is commonly performed in the knee, shoulder, elbow, and hip. However, the role it plays in the management of osteoarthritis is controversial. Routine arthroscopic management of osteoarthritis was once common, but this practice has been recently scrutinized. Although some believe that there is no role for arthroscopic treatment in the management of osteoarthritis, it may be appropriate and beneficial in certain situations. The clinical success of such treatment may be rooted in appropriate patient selection and adherence to a specific surgical technique. Arthroscopy may serve as an effective and less invasive option than traditional methods of managing osteoarthritis.

Intramedullary Nailing of Open Tibial Fractures: Provisional Plate Fixation.

Tibia fracture is the most common type of long bone fracture, and intramedullary nailing is the preferred treatment. In open fractures, a provisional plate is often used to maintain reduction. It is unknown whether this practice increases the risk of infection or other complications. This study retrospectively compared patients who were treated at a level 1 trauma center with intramedullary nailing of an open tibia fracture. Patients who were included: (1) were 18 years or older; (2) were treated between January 1, 2005, and June 30, 2013; (3) had an open fracture of the tibia; and (4) were treated operatively with intramedullary nailing, with or without provisional plate fixation. Patient sex, history of diabetes, history of smoking, mechanism of injury, and side of injury were analyzed. Postoperative complications included infection, delayed union or non-union, compartment syndrome, and death. After the authors controlled for age, Gustilo-Anderson type, and AO/Orthopaedic Trauma Association classification, they found that provisional plate use did not significantly increase the risk of infection (adjusted odds ratio, 1.64; 95% confidence interval, 0.51-5.32; P=.41) or any other complications (adjusted odds ratio, 1.24; 95% confidence interval, 0.46-3.35; P=.67). In the subgroup of patients who had a provisional plate (n=35), removal of the plate did not significantly decrease the risk of infection (adjusted odds ratio, 0.43; 95% confidence interval, 0.07-2.69; P=.36) or other complications (adjusted odds ratio, 0.55; 95% confidence interval, 0.12-2.46; P=.44). In open tibia fractures treated with intramedullary nailing, provisional plate stabilization, a valuable reduction aid, did not increase the risk of infection or other complications. Because of the small subgroup size, however, definitive conclusions cannot be drawn about removal of these provisional plates. [Orthopedics. 2016; 39(5):e931-e936.].

Driving after orthopedic surgery.

EDUCATIONAL OBJECTIVES: As a result of reading this article, physicians should be able to: (1) Identify preoperative factors that may contribute to a patient's ability to return to driving after orthopedic surgery. (2) Understand the role of upper-extremity immobilization and how it may impair a patient's ability to operate a motor vehicle. (3) Recognize how various forms of lower-extremity immobilization (e.g., controlled ankle-motion boot, cast, and Aircast Walker) affect braking reaction times and total braking times. (4) Be aware of current guidelines about when it is appropriate to return to driving following arthroscopy, lower-extremity fracture, and hip and knee arthroplasty. Few guidelines are available to assist orthopedic surgeons in advising patients about when to return to driving after orthopedic surgery. A patient's surgical procedure, postoperative weight-bearing restrictions, immobilization, and other factors influence a patient's ability to drive after orthopedic surgery. Multiple studies have used driving simulators to predict when it may be safe to return to driving after orthopedic surgery. However, study conclusions and recommendations vary significantly. This article reviews the factors contributing to a patient's ability to return to driving after orthopedic surgery and reviews recommendations based on the available literature following fracture, arthroscopy, and arthroplasty.

Nicotinamide forestalls pathology and cognitive decline in Alzheimer mice: evidence for improved neuronal bioenergetics and autophagy procession.

Impaired brain energy metabolism and oxidative stress are implicated in cognitive decline and the pathologic accumulations of amyloid ß-peptide (Aß) and hyperphosphorylated tau in Alzheimer's disease (AD). To determine whether improving brain energy metabolism will forestall disease progress in AD, the impact of the ß-nicotinamide adenine dinucleotide precursor nicotinamide on brain cell mitochondrial function and macroautophagy, bioenergetics-related signaling, and cognitive performance were studied in cultured neurons and in a mouse model of AD. Oxidative stress resulted in decreased mitochondrial mass, mitochondrial degeneration, and autophagosome accumulation in neurons. Nicotinamide preserved mitochondrial integrity and autophagy function, and reduced neuronal vulnerability to oxidative/metabolic insults and Aß toxicity. ß-Nicotinamide adenine dinucleotide biosynthesis, autophagy, and phosphatidylinositol-3-kinase signaling were required for the neuroprotective action of nicotinamide. Treatment of 3xTgAD mice with nicotinamide for 8 months resulted in improved cognitive performance, and reduced Aß and hyperphosphorylated tau pathologies in hippocampus and cerebral cortex. Nicotinamide treatment preserved mitochondrial integrity, and improved autophagy-lysosome procession by enhancing lysosome/autolysosome acidification to reduce autophagosome accumulation. Treatment of 3xTgAD mice with nicotinamide resulted in elevated levels of activated neuroplasticity-related kinases (protein kinase B [Akt] and extracellular signal-regulated kinases) and the transcription factor cyclic adenosine monophosphate (AMP) response element-binding protein in the hippocampus and cerebral cortex. Thus, nicotinamide suppresses AD pathology and cognitive decline in a mouse model of AD by a mechanism involving improved brain bioenergetics with preserved functionality of mitochondria and the autophagy system.

Evidence that OGG1 glycosylase protects neurons against oxidative DNA damage and cell death under ischemic conditions.

7,8-Dihydro-8-oxoguanine DNA glycosylase (OGG1) is a major DNA glycosylase involved in base-excision repair (BER) of oxidative DNA damage to nuclear and mitochondrial DNA (mtDNA). We used OGG1-deficient (OGG1(-/-)) mice to examine the possible roles of OGG1 in the vulnerability of neurons to ischemic and oxidative stress. After exposure of cultured neurons to oxidative and metabolic stress levels of OGG1 in the nucleus were elevated and mitochondria exhibited fragmentation and increased levels of the mitochondrial fission protein dynamin-related protein 1 (Drp1) and reduced membrane potential. Cortical neurons isolated from OGG1(-/-) mice were more vulnerable to oxidative insults than were OGG1(+/+) neurons, and OGG1(-/-) mice developed larger cortical infarcts and behavioral deficits after permanent middle cerebral artery occlusion compared with OGG1(+/+) mice. Accumulations of oxidative DNA base lesions (8-oxoG, FapyAde, and FapyGua) were elevated in response to ischemia in both the ipsilateral and contralateral hemispheres, and to a greater extent in the contralateral cortex of OGG1(-/-) mice compared with OGG1(+/+) mice. Ischemia-induced elevation of 8-oxoG incision activity involved increased levels of a nuclear isoform OGG1, suggesting an adaptive response to oxidative nuclear DNA damage. Thus, OGG1 has a pivotal role in repairing oxidative damage to nuclear DNA under ischemic conditions, thereby reducing brain damage and improving functional outcome.

The KATP channel activator diazoxide ameliorates amyloid-ß and tau pathologies and improves memory in the 3xTgAD mouse model of Alzheimer's disease.

Compromised cellular energy metabolism, cerebral hypoperfusion, and neuronal calcium dysregulation are involved in the pathological process of Alzheimer's disease (AD). ATP-sensitive potassium (KATP) channels in plasma membrane and inner mitochondrial membrane play important roles in modulating neuronal excitability, cell survival, and cerebral vascular tone. To investigate the therapeutic potential of drugs that activate KATP channels in AD, we first characterized the effects of the KATP channel opener diazoxide on cultured neurons, and then determined its ability to modify the disease process in the 3xTgAD mouse model of AD. Plasma and mitochondrial membrane potentials, cell excitability, intracellular Ca2+ levels and bioenergetics were measured in cultured cerebral cortical neurons exposed to diazoxide. Diazoxide hyperpolarized neurons, reduced the frequency of action potentials, attenuated Ca2+ influx through NMDA receptor channels, and reduced oxidative stress. 3xTgAD mice treated with diazoxide for 8 months exhibited improved performance in a learning and memory test, reduced levels of anxiety, decreased accumulation of Aß oligomers and hyperphosphorylated tau in the cortex and hippocampus, and increased cerebral blood flow. Our findings show that diazoxide can ameliorate molecular, cytopathological, and behavioral alterations in a mouse model of AD suggesting a therapeutic potential for drugs that activate KATP channels in the treatment of AD.

Nicotinamide prevents NAD+ depletion and protects neurons against excitotoxicity and cerebral ischemia: NAD+ consumption by SIRT1 may endanger energetically compromised neurons.

Neurons require large amounts of energy to support their survival and function, and are therefore susceptible to excitotoxicity, a form of cell death involving bioenergetic stress that may occur in several neurological disorders including stroke and Alzheimer's disease. Here we studied the roles of NAD(+) bioenergetic state, and the NAD(+)-dependent enzymes SIRT1 and PARP-1, in excitotoxic neuronal death in cultured neurons and in a mouse model of focal ischemic stroke. Excitotoxic activation of NMDA receptors induced a rapid decrease of cellular NAD(P)H levels and mitochondrial membrane potential. Decreased NAD(+) levels and poly (ADP-ribose) polymer (PAR) accumulation in nuclei were relatively early events (<4 h) that preceded the appearance of propidium iodide- and TUNEL-positive cells (markers of necrotic cell death and DNA strand breakage, respectively) which became evident by 6 h. Nicotinamide, an NAD(+) precursor and an inhibitor of SIRT1 and PARP1, inhibited SIRT1 deacetylase activity without affecting SIRT1 protein levels. NAD(+) levels were preserved and PAR accumulation and neuronal death induced by excitotoxic insults were attenuated in nicotinamide-treated cells. Treatment of neurons with the SIRT1 activator resveratrol did not protect them from glutamate/NMDA-induced NAD(+) depletion and death. In a mouse model of focal cerebral ischemic stroke, NAD(+) levels were decreased in both the contralateral and ipsilateral cortex 6 h after the onset of ischemia. Stroke resulted in dynamic changes of SIRT1 protein and activity levels which varied among brain regions. Administration of nicotinamide (200 mg/kg, i.p.) up to 1 h after the onset of ischemia elevated brain NAD(+) levels and reduced ischemic infarct size. Our findings demonstrate that the NAD(+) bioenergetic state is critical in determining whether neurons live or die in excitotoxic and ischemic conditions, and suggest a potential therapeutic benefit in stroke of agents that preserve cellular NAD(+) levels. Our data further suggest that, SIRT1 is linked to bioenergetic state and stress responses in neurons, and that under conditions of reduced cellular energy levels SIRT1 enzyme activity may consume sufficient NAD(+) to nullify any cell survival-promoting effects of its deacetylase action on protein substrates.

Preventing NAD(+) depletion protects neurons against excitotoxicity: bioenergetic effects of mild mitochondrial uncoupling and caloric restriction.

Neurons are excitable cells that require large amounts of energy to support their survival and functions and are therefore prone to excitotoxicity, which involves energy depletion. By examining bioenergetic changes induced by glutamate, we found that the cellular nicotinamide adenine dinucleotide (NAD(+)) level is a critical determinant of neuronal survival. The bioenergetic effects of mitochondrial uncoupling and caloric restriction were also examined in cultured neurons and rodent brain. 2, 4-dinitrophenol (DNP) is a chemical mitochondrial uncoupler that stimulates glucose uptake and oxygen consumption on cultured neurons, which accelerates oxidation of NAD(P)H to NAD(+) in mitochondria. The NAD(+)-dependent histone deacetylase sirtulin 1 (SIRT1) and glucose transporter 1 (GLUT1) mRNA are upregulated mouse brain under caloric restriction. To examine whether NAD(+) mediates neuroprotective effects, nicotinamide, a precursor of NAD(+) and inhibitor of SIRT1 and poly (ADP-ribose) polymerase 1 (PARP1) (two NAD(+)-dependent enzymes), was employed. Nicotinamide attenuated excitotoxic death and preserved cellular NAD(+) levels to support SIRT1 and PARP 1 activities. Our findings suggest that mild mitochondrial uncoupling and caloric restriction exert hormetic effects by stimulating bioenergetics in neurons thereby increasing tolerance of neurons to metabolic stress.