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Cerebrospinal Fluid Spermidine, Glutamine and Putrescine Predict Postoperative Delirium Following Elective Orthopaedic Surgery.
Pan, X, Cunningham, EL, Passmore, AP, McGuinness, B, McAuley, DF, Beverland, D, O'Brien, S, Mawhinney, T, Schott, JM, Zetterberg, H, et al
Scientific reports. 2019;(1):4191
Abstract
Delirium is a marker of brain vulnerability, associated with increasing age, pre-existing cognitive impairment and, recently, cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease. This nested case-control study used a targeted quantitative metabolomic methodology to profile the preoperative CSF of patients (n = 54) who developed delirium following arthroplasty (n = 28) and those who did not (n = 26). The aim was to identify novel preoperative markers of delirium, and to assess potential correlations with clinical data. Participants without a diagnosis of dementia (≥65 years) undergoing elective primary hip or knee arthroplasty were postoperatively assessed for delirium once-daily for three days. Groups were compared using multivariate, univariate and receiving operator characteristic (ROC) methods. Multivariate modelling using Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) of metabolomic data readily distinguished between delirium and control groups (R2 ≤ 0.56; Q2 ≤ 0.10). Three metabolites (spermidine, putrescine and glutamine) significantly differed between groups (P < 0.05; FDR < 0.07), and performed well as CSF biomarkers (ROC > 0.75). The biomarker performance of the two polyamines (spermidine/putrescine) was enhanced by ratio with CSF Aβ42 (ROC > 0.8), and spermidine significantly correlated with Aβ42 (pearson r = -0.32; P = 0.018). These findings suggest that spermidine and putrescine levels could be useful markers of postoperative delirium risk, particularly when combined with Aβ42, and this requires further investigation.
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The Inflammatory Phenotype in Failed Metal-On-Metal Hip Arthroplasty Correlates with Blood Metal Concentrations.
Paukkeri, EL, Korhonen, R, Hämäläinen, M, Pesu, M, Eskelinen, A, Moilanen, T, Moilanen, E
PloS one. 2016;(5):e0155121
Abstract
INTRODUCTION Hip arthroplasty is the standard treatment of a painful hip destruction. The use of modern metal-on-metal (MOM) bearing surfaces gained popularity in total hip arthroplasties during the last decade. Recently, worrisome failures due to adverse reaction to metal debris (ARMD), including pseudotumor response, have been widely reported. However, the pathogenesis of this reaction remains poorly understood. The aim of the present study was to investigate the ARMD response by flow cytometry approach. METHODS Sixteen patients with a failed Articular Surface Replacement (ASR) hip prosthesis were included in the study. Samples of pseudotumor tissues collected during revision surgery were degraded by enzyme digestion and cells were typed by flow cytometry. Whole blood chromium and cobalt concentrations were analyzed with mass spectrometry before revision surgery. RESULTS Flow cytometry analysis showed that the peri-implant pseudotumor tissue expressed two principal phenotypes, namely macrophage-dominated and T-lymphocyte-dominated response; the average portions being 54% (macrophages) and 25% (T-lymphocytes) in macrophage-dominated inflammation and 20% (macrophages) and 54% (T-lymphocytes) in T-lymphocyte-dominated response. The percentages of B-lymphocytes and granulocytes were lower in both phenotypes. Interestingly, the levels of blood chromium and cobalt were significantly higher in patients with macrophage-dominated response. CONCLUSIONS The results suggest that the adverse tissue reactions induced by MOM wear particles contain heterogeneous pathogeneses and that the metal levels are an important factor in the determination of the inflammatory phenotype. The present results support the hypothesis that higher metal levels cause cytotoxicity and tissue injury and macrophages are recruited to clear the necrotic debris. On the other hand, the adverse response developed in association with lower metal levels is T-lymphocyte-dominated and is likely to reflect hypersensitivity reaction.
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Prevalence of adverse reactions to metal debris following metal-on-metal THA.
Hasegawa, M, Yoshida, K, Wakabayashi, H, Sudo, A
Orthopedics. 2013;(5):e606-12
Abstract
The purpose of this study was to determine the prevalence of adverse reactions to metal debris (ARMD) following large-diameter metal-on-metal total hip arthroplasty. The authors examined the potential for using magnetic resonance imaging to screen for pseudotumors in 108 hips 2 years postoperatively. Serum cobalt and chromium concentrations were measured in 80 hips that underwent unilateral total hip arthroplasty. The authors considered pseudotumors and aseptic lymphocyte-dominated vasculitis-associated lesions to be ARMD and compared metal ion levels between hips with ARMD (ARMD group) with hips with no ARMD (non-ARMD group). Magnetic resonance imaging revealed pseudotumors in 9 patients (10 hips, 9%). Five of these 10 hips were symptomatic and underwent revision surgery. Two other patients underwent revision surgery due to symptomatic cup loosening with aseptic lymphocyte-dominated vasculitis-associated lesions. Ten patients (12 hips) had ARMD. Serum cobalt and chromium concentrations were significantly higher in hips with ARMD than hips without ARMD. Other factors, including age, body mass index, sex, clinical score, acetabular cup inclination angle, and femoral head diameter, were not significantly different between the groups. Elevated metal ion levels suggest that ARMD is associated with increased metal wear. Magnetic resonance imaging provides sensitive screening for pseudotumors following metal-on-metal total hip arthroplasty.
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Dabigatran, rivaroxaban and apixaban versus enoxaparin for thomboprophylaxis after total knee or hip arthroplasty: pool-analysis of phase III randomized clinical trials.
Nieto, JA, Espada, NG, Merino, RG, González, TC
Thrombosis research. 2012;(2):183-91
Abstract
OBJECTIVES To compare the main efficacy and safety endpoints of the pivotal randomised clinical trials (RCTs) on venous thromboembolism (VTE) prevention after total hip (THR) or knee (TKR) replacement with the new oral anticoagulants (NAs) versus enoxaparin. METHODS A pool-analysis of 10 RCTs that included 32.144 randomised patients was performed. Efficacy outcomes were total VTE and all-cause mortality, major VTE, and proximal DVT. Safety outcomes were major bleeding, and clinically relevant (major or non-major) bleeding. RESULTS Overall, a significant effect favouring NAs was found for the primary efficacy outcome (RR 0.71; 95%CI 0.56-0.90), major VTE (RR 0.59; 95%CI 0.41-0.84), and proximal DVT (RR 0.51; 95%CI 0.35-0.76). Compared to enoxaparin 40 mg QD, rivaroxaban showed superiority (RR 0.50; 95%CI 0.34-0.73), followed by apixaban (RR 0.63; 95%CI 0.36-1.01) and dabigatran (RR 1.02; 95%CI 0.86-1.20). There was significant heterogeneity among trials and subgroups analysed for these efficacy outcomes. Major bleeding (RR 1.04; 95% CI 0.74-1.46) and clinically relevant bleeding (RR 1.03; 95%CI 0.88-1.21) was similar with NAs or enoxaparin. Rivaroxaban showed a trend toward more major bleeding episodes than enoxaparin (RR 1.88; 95%CI 0.92-3.82) and apixaban showed the lowest clinically relevant bleeding risk (RR 0.81; 95%CI 0.64-1.01). CONCLUSIONS Overall, NAs showed more efficacy and same safety when compared to the recommended dose of enoxaparin after THR and TKR. There are little differences in efficacy and bleeding risk among NAs and the type of prophylaxis that should be analysed further.
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Cushion bearings versus large diameter head metal-on-metal bearings in total hip arthroplasty: a short-term metal ion study.
Moroni, A, Nocco, E, Hoque, M, Diremigio, E, Buffoli, D, Cantù, F, Catalani, S, Apostoli, P
Archives of orthopaedic and trauma surgery. 2012;(1):123-9
Abstract
INTRODUCTION Metal-on-metal total hip arthroplasty (MOM THA) has the advantage of replicating the femoral head size, but the postoperative elevation of serum metal ion levels is a cause for concern. Metal-on-polycarbonate-urethane is a new cushion bearing featuring a large diameter metal head coupled with a polycarbonate-urethane liner. AIM: The aim of this study was to assess and compare serum cobalt (Co) and chromium (Cr) levels in a group of 15 patients treated with a cushion bearing THA system (Group A) and a group of 15 patients treated with a MOM THA system (Group B) at short-term. At a mean follow-up of 27.3 months (18-35 months), in Group A the median Cr and Co serum levels were significantly lower than in Group B, measuring 0.24 μg/L (0.1-2.1 μg/L) and 0.6 μg/L (0.29-2.3 μg/L) compared to 1.3 μg/L (0.1-9 μg/L, p < 0.001) and 2.9 μg/L (0.85-13.8 μg/L, p < 0.001) respectively. RESULTS All patients demonstrated an excellent clinical result, as shown by the Harris and Oxford hip scores. The cushion bearing THA studied in this paper showed clinical outcomes similar to the MOM THA bearing, with the advantage of no significant metal ion elevation in the serum. CONCLUSION These findings warrant the continued clinical study of compliant bearing options.
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The effect of iron supplementation on the level of haemoglobin after lower limb arthroplasty.
Mundy, GM, Birtwistle, SJ, Power, RA
The Journal of bone and joint surgery. British volume. 2005;(2):213-7
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Abstract
We randomised 120 patients who were undergoing either primary total hip or knee arthroplasty to receive either ferrous sulphate or a placebo for three weeks after surgery. The level of haemoglobin and absolute reticulocyte count were measured at one and five days, and three and six weeks after operation. Ninety-nine patients (ferrous sulphate 50, placebo 49) completed the study. The two groups differed only in the treatment administered. Recovery of level of haemoglobin was similar at five days and three weeks and returned to 85% of the pre-operative level, irrespective of the treatment group. A small, albeit greater recovery in the level of haemoglobin was identified at six weeks in the ferrous sulphate group in both men (ferrous sulphate 5%, placebo 1.5%) and women (ferrous sulphate 6%, placebo 3%). The clinical significance of this is questionable and may be outweighed by the high incidence of reported side effects of oral iron and the cost of the medication. Administration of iron supplements after elective total hip or total knee arthroplasty does not appear to be worthwhile.
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Clinical outcome of salmon calcitonin nasal spray treatment in postmenopausal women after total hip arthroplasty.
Peichl, P, Griesmacher, A, Kumpan, W, Schedl, R, Prosquil, E, Bröll, H
Gerontology. 2005;(4):242-52
Abstract
OBJECTIVE The increasing rate of hip fractures is giving rise to a number of socio-economic problems for the aging community. In addition to being unable to resume their previous living habits, many patients fail to achieve full functional recovery after the fractures. Total hip arthroplasty (THA) is a successful operation for the majority of patients with all forms of hip fractures, being performed increasingly often throughout the world. Revision rates for THA range up to 20% per year. Aseptic loosening is the reason for 75% of the revisions. An additional problem post-THA is the rate of heterotopic soft tissue calcification after THA, resulting in severely impaired function, pain, and a reduced range of hip movement. SUBJECTS In an open study, 37 women who had undergone cementless THA after accidental hip fractures were treated twice daily with 200 IU of salmon calcitonin nasal spray for 12 months. Simultaneously the patients received one bag of 1,000 mg calcium plus 880 IU vitamin D daily throughout the treatment period of 1 year. A parallel group of 38 women with a similar clinical status in terms of hip fractures and cementless THA were treated with only one bag of 1,000 mg calcium plus 880 IU vitamin D daily through the treatment period. RESULTS The results of this 12-month clinical trial show that 200 IU of salmon calcitonin nasal spray per day significantly improves the clinical outcome of postmenopausal elderly women following THA. Treatment with a salmon calcitonin nasal spray significantly reduces bone turnover, loss of bone density, and pain. The functional status of the patients was improved and the risk of falling reduced by rehabilitation during the observation period of 12 months. Additionally, calcitonin promoted the repair of hip fractures and was associated with a significantly lesser rate of refractures as well as periprosthetic ossifications. CONCLUSION The increasing revision rate for THA during the first year and the patient's problem of resuming their previous living habits are the main foci of our study. Calcitonin nasal spray seems to cause few side effects. The additive treatment appears to improve the clinical outcome of THA in elderly postmenopausal women.
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Bioactive cement or ceramic/porous coating vs. conventional cement to obtain early stability of the acetabular cup. Randomised study of 96 hips followed with radiostereometry.
Digas, G, Thanner, J, Anderberg, C, Kärrholm, J
Journal of orthopaedic research : official publication of the Orthopaedic Research Society. 2004;(5):1035-43
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Abstract
Ninety patients (96 hips) scheduled for THA were stratified to fixation of the acetabular component in three main groups of about equal size. Fluoride cement, porous coated press-fit cup with ceramic coating or Palacos cum Gentamicin cement were used. All patients received Spectron EF stem. The migration of the cups and the femoral head penetration into the socket were measured with radiostereometric analysis. At 2 years the choice of fixation did not influence the migration or rotation of the cup. Patients with compromised bone quality showed increased three-dimensional (3D or total) migration. Proximal and 3D penetration rates were increased in cemented compared with the uncemented cups (p<0.001), which probably not could be related to the choice of fixation. Appearance of radiolucent lines was almost equal in the two cemented groups. Uncemented cups had less radiolucent lines at 2 years. Fluoride containing cement or uncemented fixation did not improve the early postoperative stability of the socket.
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Mid-term results of a polyethylene-free metal-on-metal articulation.
Lombardi, AV, Mallory, TH, Cuckler, JM, Williams, J, Berend, KR, Smith, TM
The Journal of arthroplasty. 2004;(7 Suppl 2):42-7
Abstract
Beginning in December 1995, 193 patients (195 hips) were enrolled into this prospective, randomized, controlled multicenter investigational device exemption study. Ninety-eight patients (99 hips) with 46 polyethylene liners and 53 metal liners had minimum 5-year follow-up (mean, 5.7 years). Average follow-up, Harris hip score improvement, and radiographic analysis were not statistically different between groups. No stress shielding or osteolysis was observed in either group. Three polyethylene liners and no metal liners had acetabular radiolucencies <1 mm in 1 or more zones. There have been no device-related complications, no acetabular revisions performed, and none pending in either group. Based on these mid-term results, the authors conclude that a metal-on-metal articulation represents a viable alternative in young, high-demand, active patients.
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Treatment of anaemia after joint replacement. A double-blind, randomised, controlled trial of ferrous sulphate versus placebo.
Sutton, PM, Cresswell, T, Livesey, JP, Speed, K, Bagga, T
The Journal of bone and joint surgery. British volume. 2004;(1):31-3
Abstract
After total hip and knee replacement arthroplasty, patients may become anaemic and may be prescribed oral iron. There is, however, no published evidence that this is of benefit when used postoperatively. We treated 72 patients who were anaemic after primary total hip and knee arthroplasty by randomly allocating them to receive six weeks of either oral ferrous sulphate (35 patients) or a placebo (37 patients). Both groups of patients were similar in all aspects except for the treatment given. There was no statistically significant difference in the change of haemoglobin levels between the two groups. We therefore believe that the prescription of iron to all anaemic patients post-operatively should be avoided. The level of serum ferritin should be monitored at preoperative assessment.