Differential Sources for 2 Neural Signatures of Target Detection: An Electrocorticography Study.

Electrophysiology and neuroimaging provide conflicting evidence for the neural contributions to target detection. Scalp electroencephalography (EEG) studies localize the P3b event-related potential component mainly to parietal cortex, whereas neuroimaging studies report activations in both frontal and parietal cortices. We addressed this discrepancy by examining the sources that generate the target-detection process using electrocorticography (ECoG). We recorded ECoG activity from cortex in 14 patients undergoing epilepsy monitoring, as they performed an auditory or visual target-detection task. We examined target-related responses in 2 domains: high frequency band (HFB) activity and the P3b. Across tasks, we observed a greater proportion of electrodes that showed target-specific HFB power relative to P3b over frontal cortex, but their proportions over parietal cortex were comparable. Notably, there was minimal overlap in the electrodes that showed target-specific HFB and P3b activity. These results revealed that the target-detection process is characterized by at least 2 different neural markers with distinct cortical distributions. Our findings suggest that separate neural mechanisms are driving the differential patterns of activity observed in scalp EEG and neuroimaging studies, with the P3b reflecting EEG findings and HFB activity reflecting neuroimaging findings, highlighting the notion that target detection is not a unitary phenomenon.

Preliminary results of a phase II randomized study to determine the efficacy and safety of genetically engineered allogeneic human chondrocytes expressing TGF-ß1 in patients with grade 3 chronic degenerative joint disease of the knee.

OBJECTIVE: The aim of this study was to preliminarily evaluate the efficacy and outcomes of injectable genetically engineered chondrocytes virally transduced with TGF-ß1 (GEC-TGF-ß1) compared to placebo. DESIGN: A multi-center, double-blinded, placebo-controlled, randomized study of adults with knee osteoarthritis. A total of 102 patients were 2:1 randomized to GEC-TGF-ß1 or placebo. Primary outcomes assessed were (1) function of the knee joint, scored using the International Knee Documentation Committee (IKDC); and (2) pain, measured by Visual Analog Scale (VAS). Secondary endpoints assessed were pain and analgesic use, quality of life (QOL), and adverse events (AEs) including need for total knee arthroplasty after treatment. RESULTS: IKDC showed significant improvement in the GEC-TGF-ß1 group over the placebo at week 12 (least mean square difference (LSMD): 10.3; P = 0.0342), week 52 (LSMD: 13.6; P = 0.0082), and overall (LSMD: 8.6; P = 0.0453). VAS Analysis showed a significant improvement in GEC-TGF-ß1 group compared to placebo at weeks 12 (LSMD: -13.8; P = 0.0162), 52 (LSMD: -13.1; P = 0.0332), and overall (LSMD: -10.1; P = 0.0350). Reduction in pain severity at week 12 and 52, frequency at 24 h and week 52, and the percentage of patients in the GEC-TGF-ß1 group receiving analgesics at week 4 (27 vs 40%) and 12 (27 vs 37%) was observed. CONCLUSIONS: GEC-TGF-ß1 patients had more positive responses on the IKDC, VAS, and were less likely to require analgesics. TRIAL NUMBER: ClinicalTrials.gov (NCT01221441) - "Study of TG-C in Patients with Grade 3 Degenerative Joint Disease of the Knee".

Molecular engineering of an orthopaedic implant: from bench to bedside.

The use of metallic implants has revolutionised the practice of orthopaedic surgery. While the safety and biocompatibility of these devices are excellent, a small percentage becomes infected. These infections are due to the formation of a biofilm that harbours bacteria encased in a complex extracellular matrix. The matrix serves as a barrier to immune surveillance as well as limiting the biocidal effects of systemic and local antibiotics. The objective of the review is to describe a novel approach to controlling implant infection using an antibiotic that is linked to titanium through a self-assembled monolayer of siloxy amines. We show that the hybrid-engineered surface is stable, biocompatible and resists colonisation by bacterial species most commonly associated with implant-related infections. Studies with rodent bone infection models suggest that the engineered titanium surface prevents bone infection. Results of a very recent investigation utilising a sheep model of infection indicate that the titanium-tethered antibiotic controls infection without compromising bone formation and remodelling. From all of these perspectives, the tethered antibiotic holds promise of providing a novel and practical approach to reducing implant-associated infections.

International Consensus Meeting on Venous Thromboembolism (ICM-VTE) after orthopedic procedures, any change in our clinical practice? / Consenso Internacional sobre Tromboembolismo Venoso (ICM-VTE) en COT, ¿cambiará en algo nuestra práctica clínica?

The International Consensus Meeting on Venous Thromboembolism (ICM-VTE), will change our current practice as most recent evidence is included. This fact is not usual in most clinical practice guidelines to date. Many orthopedic and trauma procedures do not require thromboembolic prophylaxis, but it should be considered depending on individual risk factors or major surgeries (total hip or knee arthroplasty, spine surgery or fractures that require immobilization and weight bearing restriction). Within the prophylaxis options, we must notice the strengh of the drug preventing venous thromboembolism, but also the effect of hemorrhage and bleeding that it may produce. The use of aspirin and mechanical prophylaxis has been described as the safest and most effective combination in most cases.

[Translated article] International Consensus Meeting on Venous Thromboembolism (ICM-VTE) after orthopedic procedures, any change in our clinical practice?

The International Consensus on Venous Thromboembolism (ICM-VTE), will change our current practice as most recent evidence is included. This fact is not usual in most clinical practice guidelines to date. Many orthopedic and trauma procedures do not require thromboembolic prophylaxis, but it should be considered depending on individual risk factors or major surgeries (total hip or knee arthroplasty, spine surgery or fractures that require immobilization and weight bearing restriction). Within the prophylaxis options, we must notice the strength of the drug preventing venous thromboembolism, but also the effect of hemorrhage and bleeding that it may produce. The use of aspirin and mechanical prophylaxis has been described as the safest and most effective combination in most cases.

Three-dimensional magnetic resonance imaging analysis of hip morphology in the assessment of femoral acetabular impingement.

AIM: To determine a possible association between femoral-acetabular impingement (FAI) volume and the development of labral tear using a three-dimensional (3D) model reconstruction of the acetabulum and the femoral head. MATERIALS AND METHODS: Magnetic resonance arthrography images of the hip in 42 patients with pain and suspected labral tear were acquired using a 1.5T MRI machine. Using 3D analysis software, outlines of the acetabular cup and femoral head were drawn and 3D reconstruction obtained. To control for differences in patient size, ratios of acetabulum : femoral head volume (AFV) and acetabulum : femoral head surface area (AFA) were used for analysis. The association between volume of acetabulum : femoral head and FAI was investigated using ANOVA analysis. RESULTS: There were 19 men and 23 women with a mean age of 39 years (range 18-78 years). The average AFV was 0.64 (range 0.37-1.05, SD 0.16) and AFA was 0.73 (range 0.36-1.26, SD 0.23). Herniation pit was significantly associated with a small AFV. CONCLUSION: Femoral neck herniation pits are associated with a low AFV. Gross volume and surface area ratios do not appear to correlate with labral tears or cartilage loss. This technique will enable more advanced analysis of morphological variations associated with FAI.

Preclinical animal models in single site cartilage defect testing: a systematic review.

OBJECTIVE: Review the literature for single site cartilage defect research and evaluate the respective strengths and weaknesses of different preclinical animal models. METHOD: A literature search for animal models evaluating single site cartilage defects was performed. Variables tabulated and analyzed included animal species, age and number, defect depth and diameter and study duration. Cluster analyses were then used to separate animals with only distal femoral defects into similar groups based on defect dimensions. Representative human studies were included allowing comparison of common clinical lesions to animal models. The suitability of each species for single site cartilage defect research and its relevance to clinical human practice is then discussed. RESULTS: One hundred thirteen studies relating to single site cartilage defects were reviewed. Cluster analysis included 101 studies and placed the murine, laprine, ovine, canine, porcine and caprine models in group 1. Group 2 contained ovine, canine, porcine, caprine and equine models. Group 3 contained only equine models and humans. Species in each group are similar with regard to defect dimensions. Some species occur in multiple groups reflecting utilization of a variety defect sizes. We report and discuss factors to be considered when selecting a preclinical animal model for single site cartilage defect research. DISCUSSION: Standardization of study design and outcome parameters would help to compare different studies evaluating various novel therapeutic concepts. Comparison to the human clinical counterpart during study design may help increase the predictive value of preclinical research using animal models and improve the process of developing efficacious therapies.

Biology of implant osseointegration.

Osseointegration refers to a direct structural and functional connection between ordered, living bone and the surface of a load-carrying implant. Currently, an implant is considered as osseointegrated when there is no progressive relative movement between the implant and the bone with which it has direct contact. A direct bone contact as observed histologically may be indicative of the lack of a local or systemic biological response to that surface. It is therefore proposed that osseointegration is not the result of an advantageous biological tissue response but rather the lack of a negative tissue response. The rationale of the present review is to evaluate the basic science work performed on the concept of biology of osseointegration, and to discuss the specific factors as they may relate to osseous healing around an implant.

Age alone is not a risk factor for periprosthetic joint infection.

BACKGROUND: It is not known whether age alone or the increased comorbidities in older patients are responsible for the higher rate of periprosthetic joint infection (PJI) in older patients. AIM: To test the hypothesis that age alone is not a risk factor for PJI after total joint arthroplasty. METHODS: This retrospective study included the review of 23,966 patients undergoing primary total hip and knee arthroplasty between January 1st, 2010 and December 31st, 2016 at a single institution. Patients who developed PJI, as defined by International Consensus Meeting criteria, were identified. All enrolled patients were divided into three groups that included patients aged <65 years (N = 12,761), 65-74 years (N = 6850) and ≥75 years (N = 4355). Using multivariate analysis and propensity score matching analysis, the possible association between age and PJI was examined. FINDINGS: The incidence of PJI in the entire cohort was 0.72% (171 out of 23,966). Multivariate analysis adjusting for all variables, except age, demonstrated that, compared to the patients aged <65 years, there was no statistically significant difference in the rate of PJI for patients aged 65-74 years (odds ratio: 0.89; 95% confidence interval: 0.55-1.42; P = 0.62) or for patients aged ≥75 years (0.69; 0.36-1.32; P = 0.26). CONCLUSION: When adjusting for confounding variables, age alone is not a risk factor for PJI. Studies evaluating the influence of age on the incidence of PJI should take into account the other confounding variables that contribute to PJI.

2019 John Insall Award: Fructosamine is a better glycaemic marker compared with glycated haemoglobin (HbA1C) in predicting adverse outcomes following total knee arthroplasty: a prospective multicentre study.

AIMS: The best marker for assessing glycaemic control prior to total knee arthroplasty (TKA) remains unknown. The purpose of this study was to assess the utility of fructosamine compared with glycated haemoglobin (HbA1c) in predicting early complications following TKA, and to determine the threshold above which the risk of complications increased markedly. PATIENTS AND METHODS: This prospective multi-institutional study evaluated primary TKA patients from four academic institutions. Patients (both diabetics and non-diabetics) were assessed using fructosamine and HbA1c levels within 30 days of surgery. Complications were assessed for 12 weeks from surgery and included prosthetic joint infection (PJI), wound complication, re-admission, re-operation, and death. The Youden's index was used to determine the cut-off for fructosamine and HbA1c associated with complications. Two additional cut-offs for HbA1c were examined: 7% and 7.5% and compared with fructosamine as a predictor for complications. RESULTS: Overall, 1119 patients (441 men, 678 women) were included in the study. Fructosamine level of 293 µmol/l was identified as the optimal cut-off associated with complications. Patients with high fructosamine (> 293 µmol/l) were 11.2 times more likely to develop PJI compared with patients with low fructosamine (p = 0.001). Re-admission and re-operation rates were 4.2 and 4.5 times higher in patients with fructosamine above the threshold (p = 0.005 and p = 0.019, respectively). One patient (1.7%) from the elevated fructosamine group died compared with one patient (0.1%) in the normal fructosamine group (p = 0.10). These complications remained statistically significant in multiple regression analysis. Unlike fructosamine, all three cut-offs for HbA1c failed to show a significant association with complications. CONCLUSION: Fructosamine is a valid and an excellent predictor of complications following TKA. It better reflects the glycaemic control, has greater predictive power for adverse events, and responds quicker to treatment compared with HbA1c. These findings support the screening of all patients undergoing TKA using fructosamine and in those with a level above 293 µmol/l, the risk of surgery should be carefully weighed against its benefit. Cite this article: Bone Joint J 2019;101-B(7 Supple C):3-9.

Subcortical and cortical brain activity during the feeling of self-generated emotions.

In a series of [15O]PET experiments aimed at investigating the neural basis of emotion and feeling, 41 normal subjects recalled and re-experienced personal life episodes marked by sadness, happiness, anger or fear. We tested the hypothesis that the process of feeling emotions requires the participation of brain regions, such as the somatosensory cortices and the upper brainstem nuclei, that are involved in the mapping and/or regulation of internal organism states. Such areas were indeed engaged, underscoring the close relationship between emotion and homeostasis. The findings also lend support to the idea that the subjective process of feeling emotions is partly grounded in dynamic neural maps, which represent several aspects of the organism's continuously changing internal state.

Can next generation sequencing play a role in detecting pathogens in synovial fluid?

AIMS: The diagnosis of periprosthetic joint infection can be difficult due to the high rate of culture-negative infections. The aim of this study was to assess the use of next-generation sequencing for detecting organisms in synovial fluid. MATERIALS AND METHODS: In this prospective, single-blinded study, 86 anonymized samples of synovial fluid were obtained from patients undergoing aspiration of the hip or knee as part of the investigation of a periprosthetic infection. A panel of synovial fluid tests, including levels of C-reactive protein, human neutrophil elastase, total neutrophil count, alpha-defensin, and culture were performed prior to next-generation sequencing. RESULTS: Of these 86 samples, 30 were alpha-defensin-positive and culture-positive (Group I), 24 were alpha-defensin-positive and culture-negative (Group II) and 32 were alpha-defensin-negative and culture-negative (Group III). Next-generation sequencing was concordant with 25 results for Group I. In four of these, it detected antibiotic resistant bacteria whereas culture did not. In another four samples with relatively low levels of inflammatory biomarkers, culture was positive but next-generation sequencing was negative. A total of ten samples had a positive next-generation sequencing result and a negative culture. In five of these, alpha-defensin was positive and the levels of inflammatory markers were high. In the other five, alpha-defensin was negative and the levels of inflammatory markers were low. While next-generation sequencing detected several organisms in each sample, in most samples with a higher probability of infection, there was a predominant organism present, while in those presumed not to be infected, many organisms were identified with no predominant organism. CONCLUSION: Pathogens causing periprosthetic infection in both culture-positive and culture-negative samples of synovial fluid could be identified by next-generation sequencing. Cite this article: Bone Joint J 2018;100-B:127-33.

Increased postoperative glucose variability is associated with adverse outcomes following orthopaedic surgery.

Aims: The aim of this study was to examine the association between postoperative glycaemic variability and adverse outcomes following orthopaedic surgery. Patients and Methods: This retrospective study analyzed data on 12 978 patients (1361 with two operations) who underwent orthopaedic surgery at a single institution between 2001 and 2017. Patients with a minimum of either two postoperative measurements of blood glucose levels per day, or more than three measurements overall, were included in the study. Glycaemic variability was assessed using a coefficient of variation (CV). The length of stay (LOS), in-hospital complications, and 90-day readmission and mortality rates were examined. Data were analyzed with linear and generalized linear mixed models for linear and binary outcomes, adjusting for various covariates. Results: The cohort included 14 339 admissions, of which 3302 (23.0%) involved diabetic patients. Patients with CV values in the upper tertile were twice as likely to have an in-hospital complication compared with patients in the lowest tertile (19.4% versus 9.0%, p < 0.001), and almost five times more likely to die compared with those in the lowest tertile (2.8% versus 0.6%, p < 0.001). Results of the adjusted analyses indicated that the mean LOS was 1.28 days longer in the highest versus the lowest CV tertile (p < 0.001), and the odds of an in-hospital complication and 90-day mortality in the highest CV tertile were respectively 1.91 (p < 0.001) and 2.10 (p = 0.001) times larger than the odds of these events in the lowest CV tertile. These associations were significant even for non-diabetic patients. After adjusting for hypoglycaemia, the relationships remained significant, except that the CV tertile no longer predicted mortality in diabetics. Conclusion: These results indicate that higher glycaemic variability is associated with longer LOS and in-hospital complications. Glycaemic variability also predicted death, although that primarily held for non-diabetic patients in the highest CV tertile following orthopaedic surgery. Prospective studies should examine whether ensuring low postoperative glycaemic variability may reduce complication rates and mortality. Cite this article: Bone Joint J 2018;100-B:1125-32.

Venous thromboembolic prophylaxis after simultaneous bilateral total knee arthroplasty: aspirin versus warfarin.

AIMS: The aims of this study were to compare the efficacy of two agents, aspirin and warfarin, for the prevention of venous thromboembolism (VTE) after simultaneous bilateral total knee arthroplasty (SBTKA), and to elucidate the risk of VTE conferred by this procedure compared with unilateral TKA (UTKA). PATIENTS AND METHODS: A retrospective, multi-institutional study was conducted on 18 951 patients, 3685 who underwent SBTKA and 15 266 who underwent UTKA, using aspirin or warfarin as VTE prophylaxis. Each patient was assigned an individualised baseline VTE risk score based on a system using the Nationwide Inpatient Sample. Symptomatic VTE, including pulmonary embolism (PE) and deep vein thrombosis (DVT), were identified in the first 90 days post-operatively. Statistical analyses were performed with logistic regression accounting for baseline VTE risk. RESULTS: The adjusted incidence of PE following SBTKA was 1.0% (95% confidence interval (CI) 0.86 to 1.2) with aspirin and 2.2% (95% CI 2.0 to 2.4) with warfarin. Similarly, the adjusted incidence of VTE following SBTKA was 1.6% (95% CI 1.1 to 2.3) with aspirin and 2.5% (95% CI 1.9 to 3.3) with warfarin. The risk of PE and VTE were reduced by 66% (odds ratio (OR) 0.44, 95% CI 0.25 to 0.78) and 38% (OR 0.62, 95% CI 0.38 to 1.0), respectively, using aspirin. In addition, the risk of PE was 204% higher for patients undergoing SBTKA relative to those undergoing UTKA. For each ten-point increase in baseline VTE risk, the risk of PE increased by 25.5% for patients undergoing SBTKA compared with 10.5% for those undergoing UTKA. Patients with a history of myocardial infarction or peripheral vascular disease had the greatest increase in risk from undergoing SBTKA instead of UTKA. CONCLUSION: Aspirin is more effective than warfarin for the prevention of VTE following SBTKA, and serves as the more appropriate agent for VTE prophylaxis for patients in all risk categories. Furthermore, patients undergoing SBTKA are at a substantially increased risk of VTE, even more so for those with significant underlying risk factors. Patients should be informed about the risks associated with undergoing SBTKA. Cite this article: Bone Joint J 2018;100-B(1 Supple A):68-75.

Prevention of periprosthetic joint infection: new guidelines.

The World Health Organization (WHO) and the Centre for Disease Control and Prevention (CDC) recently published guidelines for the prevention of surgical site infection. The WHO guidelines, if implemented worldwide, could have an immense impact on our practices and those of the CDC have implications for healthcare policy in the United States. Our aim was to review the strategies for prevention of periprosthetic joint infection in light of these and other recent guidelines. Cite this article: Bone Joint J 2017;99-B(4 Supple B):3-10.

Aspirin and the prevention of venous thromboembolism following total joint arthroplasty: commonly asked questions.

The number of arthroplasties being performed increases each year. Patients undergoing an arthroplasty are at risk of venous thromboembolism (VTE) and appropriate prophylaxis has been recommended. However, the optimal protocol and the best agent to minimise VTE under these circumstances are not known. Although many agents may be used, there is a difference in their efficacy and the risk of bleeding. Thus, the selection of a particular agent relies on the balance between the desire to minimise VTE and the attempt to reduce the risk of bleeding, with its undesirable, and occasionally fatal, consequences. Acetylsalicylic acid (aspirin) is an agent for VTE prophylaxis following arthroplasty. Many studies have shown its efficacy in minimising VTE under these circumstances. It is inexpensive and well-tolerated, and its use does not require routine blood tests. It is also a 'milder' agent and unlikely to result in haematoma formation, which may increase both the risk of infection and the need for further surgery. Aspirin is also unlikely to result in persistent wound drainage, which has been shown to be associated with the use of agents such as low-molecular-weight heparin (LMWH) and other more aggressive agents. The main objective of this review was to summarise the current evidence relating to the efficacy of aspirin as a VTE prophylaxis following arthroplasty, and to address some of the common questions about its use. There is convincing evidence that, taking all factors into account, aspirin is an effective, inexpensive, and safe form of VTE following arthroplasty in patients without a major risk factor for VTE, such as previous VTE. Cite this article: Bone Joint J 2017;99-B:1420-30.

Consenso Internacional sobre Tromboembolismo Venoso (ICM-VTE) en COT, cambiará en algo nuestra práctica clínica? / International Consensus Meeting on Venous Thromboembolism (ICM-VTE) after orthopedic procedures, any change in our clinical practice?

Las aportaciones del Consenso Internacional sobre Tromboembolismo Venoso (ICM-VTE) modificarán nuestra práctica diaria, recogiendo la evidencia actual que no aparece en la mayoría de las guías de práctica clínica hasta la fecha. Muchos de nuestros procedimientos de cirugía ortopédica y traumatología no requieren de una profilaxis tromboembólica que solo se administra cuando existen factores de riesgos individuales o cirugías mayores (artroplastia total de miembros inferiores, cirugía de columna o fracturas que requieran inmovilización y limitación en la carga precoz). Dentro de las opciones de profilaxis debemos tener en cuenta la potencia del fármaco para prevenir el tromboembolismo venoso, pero también el efecto de hemorragia y sangrado que pueda producir. El uso de aspirina y medidas mecánicas se establece como la combinación más segura y eficaz en muchos de los casos.(AU)

The International Consensus Meeting on Venous Thromboembolism (ICM-VTE), will change our current practice as most recent evidence is included. This fact is not usual in most clinical practice guidelines to date. Many orthopedic and trauma procedures do not require thromboembolic prophylaxis, but it should be considered depending on individual risk factors or major surgeries (total hip or knee arthroplasty, spine surgery or fractures that require immobilization and weight bearing restriction). Within the prophylaxis options, we must notice the strengh of the drug preventing venous thromboembolism, but also the effect of hemorrhage and bleeding that it may produce. The use of aspirin and mechanical prophylaxis has been described as the safest and most effective combination in most cases.(AU)

[Translated article] International Consensus Meeting on Venous Thromboembolism (ICM-VTE) after orthopedic procedures, any change in our clinical practice? / Consenso Internacional sobre Tromboembolismo Venoso (ICM-VTE) en COT, cambiará en algo nuestra práctica clínica?

Las aportaciones del Consenso Internacional sobre Tromboembolismo Venoso (ICM-VTE) modificarán nuestra práctica diaria, recogiendo la evidencia actual que no aparece en la mayoría de las guías de práctica clínica hasta la fecha. Muchos de nuestros procedimientos de cirugía ortopédica y traumatología no requieren de una profilaxis tromboembólica que solo se administra cuando existen factores de riesgos individuales o cirugías mayores (artroplastia total de miembros inferiores, cirugía de columna o fracturas que requieran inmovilización y limitación en la carga precoz). Dentro de las opciones de profilaxis debemos tener en cuenta la potencia del fármaco para prevenir el tromboembolismo venoso, pero también el efecto de hemorragia y sangrado que pueda producir. El uso de aspirina y medidas mecánicas se establece como la combinación más segura y eficaz en muchos de los casos.(AU)

The International Consensus Meeting on Venous Thromboembolism (ICM-VTE), will change our current practice as most recent evidence is included. This fact is not usual in most clinical practice guidelines to date. Many orthopedic and trauma procedures do not require thromboembolic prophylaxis, but it should be considered depending on individual risk factors or major surgeries (total hip or knee arthroplasty, spine surgery or fractures that require immobilization and weight bearing restriction). Within the prophylaxis options, we must notice the strengh of the drug preventing venous thromboembolism, but also the effect of hemorrhage and bleeding that it may produce. The use of aspirin and mechanical prophylaxis has been described as the safest and most effective combination in most cases.(AU)