The aim of this study was to identify patient- and surgery-related risk factors for sustaining an early periprosthetic fracture following primary total hip arthroplasty (THA) performed using a ...double-tapered cementless femoral component (Bi-Metric femoral stem; Biomet Inc., Warsaw, Indiana).
A total of 1598 consecutive hips, in 1441 patients receiving primary THA between January 2010 and June 2015, were retrospectively identified. Level of pre-operative osteoarthritis, femoral Dorr type and cortical index were recorded. Varus/valgus placement of the stem and canal fill ratio were recorded post-operatively. Periprosthetic fractures were identified and classified according to the Vancouver classification. Regression analysis was performed to identify risk factors for early periprosthetic fracture.
The mean follow-up was 713 days (1 to 2058). A total of 48 periprosthetic fractures (3.0%) were identified during the follow-up and median time until fracture was 16 days, (interquartile range 10 to 31.5). Patients with femoral Dorr type C had a 5.2 times increased risk of post-operative periprosthetic fracture compared with type B, while female patients had a near significant two times increased risk over time for post-operative fracture.
Dorr type C is an independent risk factor for early periprosthetic fracture, following THA using a double tapered cementless stem such as the Bi-Metric. Surgeons should take bone morphology into consideration when planning for primary THA and consider using cemented femoral components in female patients with poor bone quality. Cite this article:
2017;99-B:451-7.
High-dose glucocorticoid may reduce postsurgical pain and improve recovery. We hypothesized that 125 mg methylprednisolone (MP) would reduce time to meet functional discharge criteria after total hip ...arthroplasty (THA).
Forty-eight patients undergoing unilateral THA under spinal anaesthesia were consecutively included in this randomized, double-blind, placebo-controlled trial receiving preoperative i.v. MP or saline. All patients received a standardized, multimodal analgesic regime with paracetamol, celecoxib, and gabapentin. The primary outcome was time to meet well-defined functional discharge criteria. Secondary outcomes were handgrip strength and endurance, pain, nausea, vomiting, fatigue, sleep quality, and rescue analgesic-, antiemetic-, and hypnotic medicine requirements. The inflammatory response measured by C-reactive protein (CRP) and actual length of stay were also registered. Discharge criteria were assessed twice daily (at 09:00 and 14:00 h) until discharge. Other outcomes were assessed at 2, 4, 6, 8, and 24 h after operation, and also in a questionnaire from postoperative day (POD) 1–4.
Time to meet discharge criteria was median (IQR) (95% CI), MP vs placebo: 23.5 (23.3–23.7) (17.8–43.8) vs 23.5 (23.0–23.8) (20.0–46.8) h, the mean difference (95% CI) being −1.3 (−4.7 to 2.2) h, P=0.65. Overall pain for the first 24 h after surgery was significantly reduced in the MP vs the placebo group (P<0.01), as was CRP at 24 h (P<0.0001). No other between-group differences were observed. No drug-related complications were observed at follow-up on POD30.
MP 125 mg i.v. before surgery added to a multimodal oral analgesic regime did not reduce time to meet functional discharge criteria after THA, but improved analgesia for the first 24 h.
To investigate firstly the efficacy of three different dosages of one home-based, knee-extensor resistance exercise on knee-extensor strength in patients eligible for knee replacement, and secondly, ...the influence of exercise on symptoms, physical function and decision on surgery.
One-hundred and forty patients eligible for knee replacement were randomized to three groups: 2, 4 or 6 home-based knee-extensor resistance exercise-sessions per week (group 2, 4 and 6 respectively) for 12 weeks. Primary outcome: isometric knee-extensor strength. Secondary outcomes: Oxford Knee Score, Knee injury and Osteoarthritis Outcome Score, average knee pain last week (0–10 numeric rating scale), 6-min walk test, stair climbing test, exercise adherence and “need for surgery”.
Primary analysis: Intention-to-treat analysis of 140 patients did not find statistically significant differences between the groups from baseline to after 12 weeks of exercise in isometric knee-extensor strength: Group 2 vs 4 (0.003 Nm/kg (0.2%) 95% CI -0.15 to 0.15, P = 0.965) and group 4 vs 6 (−0.04 Nm/kg (−2.7%) 95% CI -0.15 to 0.12, P = 0.628). Secondary analysis: Intention-to-treat analyses showed statistically significant differences between the two and six sessions/week groups in favor of the two sessions/week group for Oxford Knee Score: 4.8 OKS points (15.2%) 1.3 to 8.3, P = 0.008) and avg. knee pain last week (NRS 0–10): −1.3 NRS points (−19.5%) -2.3 to −0.2, P = 0.018. After the 12-week exercise intervention, data were available for 117 patients (N = 39/group): 38 (32.5%) patients wanted surgery and 79 (67.5%) postponed surgery. This was independent of exercise dosage.
In patients eligible for knee-replacement we found no between-group differences in isometric knee extensor strength after 2, 4 and 6 knee-extensor resistance exercise sessions per week. We saw no indication of an exercise dose–response relationship for isometric knee-extensor strength and only clinically irrelevant within group changes. For some secondary outcome (e.g., KOOS subscales) we found clinically relevant within group changes, which could help explain why only one in three patients decided to have surgery after the simple home-based exercise intervention.
ClinicalTrials.gov identifier: NCT02931058. Preprint: https://doi.org/10.1101/2021.04.07.21254965.
Total knee arthroplasty (TKA) is associated with severe pain and inflammation despite an extensive multimodal analgesic approach, but the effect of high-dose glucocorticoid administration has not ...been studied.
Forty-eight patients undergoing unilateral TKA were included in a randomized, double-blind, placebo-controlled trial receiving preoperative methylprednisolone (MP) 125 mg i.v. or saline. All surgery was performed under lumbar spinal anaesthesia and patients received a standardized, multimodal analgesic regime. The primary endpoint was pain during walking 24 h after surgery, and secondary endpoints were pain at rest, pain upon hip flexion, and pain upon knee flexion. Pain assessments were performed repeatedly for the first 48 h after surgery, in a questionnaire from days 2 to 10, and at follow-up on days 21 and 30. Tertiary endpoints were postoperative nausea and vomiting (PONV), plasma C-reactive protein (CRP) concentrations, fatigue, sleep quality, and rescue analgesic and antiemetic requirements.
Pain during walking was significantly lower in the MP group up to 32 h after operation. Overall pain and cumulative pain scores (2–48 h) were lower for all pain assessments (P<0.04). Consumption of rescue oxycodone was lower from 0 to 24 h (P=0.02) and PONV, consumption of ondansetron reduced (P<0.05), and CRP concentrations were lower at 24 h (P<0.000001). Fatigue throughout the day of surgery was lower (P=0.02), but sleep quality was worse on the first night (P=0.002). No side-effects or complications were observed in other respects.
MP 125 mg before surgery improves analgesia and immediate recovery after TKA, even when combined with a multimodal analgesic regime. These findings call for further studies on safety aspects.
Registered with ClinicalTrails.gov under the US National Library of Medicine (registration number: NCT00968578).
Tau is a microtubule (MT)-stabilizing protein that is altered in Alzheimer's disease (AD) and other tauopathies. It is hypothesized that the hyperphosphorylated, conformationally altered, and ...multimeric forms of tau lead to a disruption of MT stability; however, direct evidence is lacking in vivo. In this study, an in vivo stable isotope-mass spectrometric technique was used to measure the turnover, or dynamicity, of MTs in brains of living animals. We demonstrated an age-dependent increase in MT dynamics in two different tau transgenic mouse models, 3xTg and rTg4510. MT hyperdynamicity was dependent on tau expression, since a reduction of transgene expression with doxycycline reversed the MT changes. Treatment of rTg4510 mice with the epothilone, BMS-241027, also restored MT dynamics to baseline levels. In addition, MT stabilization with BMS-241027 had beneficial effects on Morris water maze deficits, tau pathology, and neurodegeneration. Interestingly, pathological and functional benefits of BMS-241027 were observed at doses that only partially reversed MT hyperdynamicity. Together, these data suggest that tau-mediated loss of MT stability may contribute to disease progression and that very low doses of BMS-241027 may be useful in the treatment of AD and other tauopathies.
Summary
In a well‐defined fast‐track setup for total hip and knee arthroplasty, with a multimodal analgesic regimen consisting of intra‐operative local anaesthetic infiltration and oral celecoxib, ...gabapentin and paracetamol for 6 days postoperatively, we conducted a prospective, consecutive, observational study. The purpose was to describe the prevalence and intensity of subacute postoperative pain and opioid related side effects, use of analgesics and functional ability 1–10 and 30 days postoperatively. Fast‐track total hip and knee arthroplasty with early discharge (< 3 days) resulted in acceptable levels of pain and postoperative nausea and vomiting with concomitant low use of opioids in > 95% of patients after discharge before day 10 after total hip arthroplasty. However, after total knee arthroplasty 52% patients reported moderate pain (VAS 30–59 mm), and 16% severe pain (VAS ≥ 60 mm) when walking 1 month after surgery with a concomitant increase in the use of strong opioids. These results emphasise the need for improvement in analgesia after discharge following total knee arthroplasty, to facilitate rehabilitation.
Background: High‐volume infiltration analgesia may be effective with a low risk of side effects in hip and knee arthroplasty. The present placebo‐controlled study was carried out to evaluate the ...analgesic effect of high‐volume infiltration analgesia in bilateral total knee arthroplasty, along with a detailed description of the infiltration technique.
Methods: In a randomized, double‐blind, placebo‐controlled trial in 12 patients undergoing bilateral knee arthroplasty, saline or high‐volume (170 ml) ropivacaine (0.2%) with epinephrine was infiltrated around each knee, with repeated doses administered through an intra‐articular catheter for 24 h and pain and opioid requirements assessed for 48 h in a fast‐track setting.
Results: Pain at rest and during movement was significantly reduced for up to 32 h with the high‐volume local anesthetic infiltration technique. No major side effects were observed. The median hospital stay was 4 days.
Conclusion: High‐volume infiltration analgesia is effective in knee arthroplasty and, due to its simplicity, may be preferable compared with other analgesic techniques in knee arthroplasty.
Abstract Synaptic plasticity plays a crucial role in learning, memory, and cognitive disorders. Cytoskeletal reorganization underlies neuronal synaptic plasticity, but little is known about the ...regulation of cytoskeletal dynamics in living animals. We used stable isotope labeling to measure the turnover of tubulin in defined microtubule (MT) populations in murine brain. Neuronal MTs generally exhibited low turnover rates in vivo . Basal turnover was highest in tau-associated MTs, intermediate in microtubule-associated protein 2 (MAP2)–associated MTs, and lowest in cold-stable MTs. Labeling of MTs in mature neurons in cell culture yielded similar turnover results. Intracerebroventricular glutamate injection stimulated, via N -methyl- d -aspartic acid receptors, label incorporation (turnover) in cold-stable, tau-associated, and MAP2-associated MTs, the last of which was shown to be dependent on cyclic adenosine-3′, 5′-monophosphorothioate–protein kinase A. Contextual fear conditioning, a hippocampus-mediated form of memory formation, was accompanied by increased turnover of hippocampal MAP2-associated and cold-stable MTs. Treatment with the MT-depolymerizing drug nocodazole reversed the conditioning-induced increase in label incorporation in MAP2-associated MTs, reduced dendritic spine density, and impaired memory formation. The effects of nocodazole on MT turnover were prevented by the MT-stabilizing agent Taxol (Sigma-Aldrich, St. Louis, MO, USA) and by brain-derived nerve growth factor, both of which also restored dendritic spine density and memory formation in this model. In conclusion, these results suggest that changes in hippocampal MT turnover are required for, and are a biomarker of, the synaptic plasticity that is involved in memory formation.
Purpose
The Forgotten Joint Score (FJS) is a novel measurement for patients’ awareness of their knee in daily life. By identifying factors that could explain pre-operative FJS levels, the clinician ...could better prioritize and single out patients who would benefit most from TKA. The aim of this study was to identify possible factors that may explain the variance of pre-operative FJS levels and evaluate the relationship between pre-operative FJS and pre-operative Oxford Knee Score (OKS).
Methods
Four-hundred and six individual knees undergoing primary TKA between 2014 and 2016 were included in the study. Age, gender, body mass index (BMI), pre-operative FJS and pre-operative OKS were obtained maximum 2 weeks prior to surgery. Kellgren–Lawrence (K–L) grade, alignment and joint space width (JSW) were evaluated on pre-operative radiographs.
Results
Mean FJS was 21.1 ± 15.6. Females, younger patients and patients with high BMI had significantly the worst pre-operative FJS
(p
< 0.005). Females scored 6.5 FJS points lower than males. A 0.2-point increase in FJS for every added year indicated improvement in knee awareness with age. A 0.4-point decrease in FJS points for every added BMI point indicated worse knee awareness with higher BMI. There was a strong positive correlation between pre-operative FJS and pre-operative OKS according to the Spearman’s rank order test
(p
< 0.005).
Conclusions
Females, younger patients and patients with high BMI had significantly the worst pre-operative joint awareness. FJS had a strong positive correlation to OKS in pre-operative patients for primary TKA. This information can be used for improved patient selection; clinically continuous low FJS despite weight loss and/or the passing of time may be indication for TKA.
Level of evidence
Prospective cohort study, Level II.
Mutations in copper/zinc superoxide dismutase 1 (SOD1), a genetic cause of human amyotrophic lateral sclerosis, trigger motoneuron death through unknown toxic mechanisms. We report that transgenic ...SOD1G93A mice exhibit striking and progressive changes in neuronal microtubule dynamics from an early age, associated with impaired axonal transport. Pharmacologic administration of a microtubule-modulating agent alone or in combination with a neuroprotective drug to symptomatic SOD1G93A mice reduced microtubule turnover, preserved spinal cord neurons, normalized axonal transport kinetics, and delayed the onset of symptoms, while prolonging life by up to 26%. The degree of reduction of microtubule turnover was highly predictive of clinical responses to different treatments. These data are consistent with the hypothesis that hyperdynamic microtubules impair axonal transport and accelerate motor neuron degeneration in amyotrophic lateral sclerosis. Measurement of microtubule dynamics in vivo provides a sensitive biomarker of disease activity and therapeutic response and represents a new pharmacologic target in neurodegenerative disorders.