Primary care patient interests in joining a planned multi-cancer early detection clinical trial.

INTRODUCTION: Clinical trials are being conducted and are being planned to assess the safety and efficacy of multi-cancer early detection (MCED) tests for use in cancer screening. This study aimed to determine the feasibility of primary care patient outreach in recruiting participants to a planned MCED clinical trial, assess patient interest in trial participation, and measure decisional conflict related to participation. METHODS: The research team used the electronic medical record of a large, urban health care system to identify primary care patients 50-80 years of age who were potentially eligible for a planned MCED trial. We mailed information about the planned MCED trial to identified patients and then contacted the patients by telephone to obtain consent and administer a baseline survey. Subsequently, we contacted consented patients to complete an interview to review the mailed information and elicit perceptions about trial participation. Finally, a research coordinator administered an endpoint telephone survey to assess patient interest in and decisional conflict related to joining the trial. RESULTS: We randomly identified 1000 eligible patients and were able to make contact with 690 (69%) by telephone. Of the patients contacted, 217 (31%) completed the decision counseling session and 219 (32%) completed the endpoint survey. Among endpoint survey respondents, 177 (81%) expressed interest in joining the MCED trial and 162 (74%) reported low decisional conflict. CONCLUSIONS: Most patients were contacted and about a quarter of those contacted expressed interest in and low decisional conflict about joining the planned MCED trial. Research is needed to determine how to optimize patient outreach and engage patients in shared decision-making about MCED trial participation.

Primary Care Provider Receptivity to Multi-Cancer Early Detection Test Use in Cancer Screening.

Multi-cancer early detection tests (MCEDs) are blood-based tests that detect biomarkers released or induced by cancer cells. If MCED tests are shown to be safe and effective in cancer screening, they are likely to be ordered and managed in primary care. To understand primary care providers' support for and concerns about the implementation and management of MCED testing, the research team developed a cross-sectional survey that was sent to 939 primary care providers (physicians, residents/fellows, and advanced practice providers) in a large academic health system in the greater Philadelphia area. The survey included standard items used to assess provider background characteristics and to measure provider awareness of challenges related to MCED test use (7 items), perceived competence in MCED testing (5 items), and receptivity to MCED test use in the future (4 items). A total of 351 (37.4%) primary care providers completed the survey. Among respondents, the awareness of challenges in MCED testing (mean = 3.95, sd = 0.64), perceived competence (3.67, sd = 0.85), and receptivity to MCED use in practice (mean = 3.62, 0.75) were moderately high. Multiple regression was performed to identify factors associated with receptivity to MCED testing. We found that provider number of years in practice (DATA), awareness of challenges related to MCED testing (DATA), and perceived competence in MCED test use (DATA) were positively and significantly associated with receptivity to MCED test use in practice. An exploratory factor analysis extracted two components: receptivity to MCEDs and awareness of challenges. Surprisingly, these factors had a positive correlation (r = 0.124, p = 0.024). Providers' perceived competence in using MCED tests and providers' experience level were significantly associated with receptivity to MCED testing. While there was strong agreement with potential challenges to implementing MCEDs, PCPs were generally receptive to using MCEDs in cancer screening. Keeping PCPs updated on the evolving knowledge of MCEDs is likely critical to building receptivity to MCED testing.

Primary Care Patient Interest in Multi-Cancer Early Detection for Cancer Screening.

Multi-cancer early detection (MCED) tests are being developed, but little is known about patient receptivity to their use for cancer screening. The current study assessed patient interest in such testing. Our team conducted a prospective, observational study among primary care patients in a large, urban health system. They were asked to complete a telephone survey that briefly described a new blood test in development to identify multiple types of cancer, but was not currently recommended or covered by insurance. The survey included items to assess respondent background characteristics, perceptions about MCED testing, and interest in having such an MCED test. We also used multivariable analyses to identify factors associated with patient interest in test use. In 2023, we surveyed 159 (32%) of 500 identified patients. Among respondents, 125 (79%) reported a high level of interest in having an MCED test. Interest was not associated with personal background characteristics, but was positively associated with the following expectations: testing would be recommended for cancer screening, be convenient, and be effective in finding early-stage disease (OR = 11.70, 95% CI: 4.02, 34.04, p < 0.001). Research is needed to assess patient interest and actual uptake when detailed information on testing is presented in routine care.

Corticosteroid Injections for Symptomatic Treatment of Osteoarthritis of the Knee: A Pilot Blinded Randomized Trial.

OBJECTIVE: To quantify the effect of corticosteroids compared to lidocaine-only injections over 12 weeks among patients with knee osteoarthritis (KOA). METHODS: Participants with KOA were randomized to receive a knee injection of methylprednisolone acetate 1 mL (40 mg) plus 2 mL lidocaine (1%) or 1 mL saline and 2 mL lidocaine. Participants and providers were blinded to treatment allocation using an opacified syringe. The outcome was the average change from baseline of the total Knee Injury and Osteoarthritis Outcome Score (KOOS) (range 0-100) assessed at 2-week intervals over 12 weeks. Participants received KOOS questionnaires on their smartphones through a web-based platform. We used linear mixed-effects regressions with robust variance estimators to evaluate the association between the intervention and change in KOOS total and subscales (ClinicalTrials.gov identifier NCT03835910; registered 2019-02-11). RESULTS: Of the 33 randomized participants, 31 were included in the final analysis. The predicted mean (SE) change in total KOOS over the 12-week follow-up was 9.4 (3.2) in the corticosteroids arm versus -1.3 (1.4) in the control arm (P = 0.003). Of participants, 47% achieved change as large as the minimal clinically important difference (16 units) in the intervention arm compared to 6% of participants in the lidocaine arm. Further, there were greater improvements in the intervention arm for KOOS subscales and for Patient Reported Outcomes Measurement Information System (PROMIS) assessments of pain intensity, behavior, and interference. CONCLUSION: Corticosteroid injections demonstrated clinically meaningful improvements in KOA symptoms over 12 weeks of follow-up. These data support larger studies to better quantify short-term benefits.

Protocol for a multi-center randomized controlled trial to evaluate the benefits of exercise incentives and corticosteroid injections in osteoarthritis of the knee (MOVE-OK).

BACKGROUND: Knee osteoarthritis (KOA) is a high-priority problem among the aging population. While exercise has been shown to be beneficial in management of the disease, scalable and low-cost interventions to improve exercise in this population are lacking. Recent controversy over the value of corticosteroid injections for palliation has also arisen. Therefore, we designed a randomized, double-blind, placebo-controlled clinical trial with a 2-period crossover design to study (1) behavioral incentives to promote exercise and (2) corticosteroid injections to reduce pain and improve function in patients with KOA when compared to lidocaine only. METHODS: The study design is a pragmatic factorial and crossover randomized clinical trial. Patients with KOA who are deemed eligible by their provider to receive knee injections and are able to walk without assistive devices will be recruited from clinical practices at four sites within the Veterans Affairs (VA) Health System in the USA. In total, 220 participants will be randomized to receive social incentives with gamification (i.e., incorporation of game elements) to promote exercise and compared to controls that receive a Fitbit but no incentive. Each patient will also be assigned to receive a blinded corticosteroid injection and a lidocaine-only injection in random order. The primary outcomes are the change in average daily step counts from baseline and the change in Knee Osteoarthritis Outcome Score (KOOS) from baseline. The study team will continuously collect step count, heart rate, and sleep data using activity monitors and patient-reported outcomes using the Way to Health (WTH) platform at two four-week intervals over eight months of follow-up. Mixed effects regression incorporating all available data points will be used for analysis. DISCUSSION: The "Marching on for Veterans with Osteoarthritis of the Knee" (MOVE-OK) trial will take a pragmatic approach to evaluate (1) whether incentives based on behaviorally enhanced gamification can improve physical activity in this patient population and (2) whether corticosteroids injections reduce pain and disability in patients with KOA. Results of this trial will help to direct clinical practice and inform management guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT05035810 . Registered on 5 September 2021.

Understanding components of embodiment: Evidence from the mirror box illusion.

Past studies have examined embodiment in the rubber hand illusion, using principal components analysis (PCA) to identify factors from questionnaire responses during synchronous and asynchronous stroking. To better understand the phenomenology of embodiment, we used PCA in the mirror box illusion to examine performance across conditions that varied in movement synchrony to examine multisensory integration and movement type to vary the amount of multisensory congruence. We found three dissociable components in all conditions: embodiment, deafference and attentiveness. We also examined how these embodiment ratings varied across the four conditions. As hypothesized, embodiment ratings were highest for synchronous movement, with feelings of deafference highest for asynchronous movement. Furthermore, there was a movement by timing interaction, such that sliding resulted in greater differences in synchronous versus asynchronous ratings than tapping. These results suggest that embodiment or deafference can be changed as a function of the amount of multisensory congruence.

Vancomycin Wrap for Anterior Cruciate Ligament Surgery: Molecular Insights.

BACKGROUND: The use of the vancomycin wrap to pretreat the hamstring graft in anterior cruciate ligament reconstruction (ACLR) has grown in popularity since it was first described in 2012 and has significantly reduced rates of postoperative infection. However, it remains unknown if this antibiotic treatment affects the molecular composition of the graft. PURPOSE: To establish whether treatment with vancomycin at 5 mg/mL, the most commonly used concentration, alters the molecular function of the hamstring graft in ACLR. STUDY DESIGN: Controlled laboratory study. METHODS: Surplus hamstring tendon collected after routine ACLR surgery was used for in vitro cell culture and ex vivo tissue experiments. Vancomycin was used at 5 mg/mL in RPMI or saline diluent to treat cells and tendon tissue, respectively, with diluent control conditions. Cell viability at 30, 60, and 120 minutes was assessed via colorimetric viability assay. Tendon cells treated with control and experimental conditions for 1 hour was evaluated using semiquantitative reverse transcription analysis, immunohistochemistry staining, and protein quantitation via enzyme-linked immunosorbent assay for changes in apoptotic, matrix, and inflammatory gene and protein expression. RESULTS: Vancomycin treatment at 5 mg/mL significantly reduced tenocyte viability in vitro after 60 minutes of treatment (P < .05); however, this was not sustained at 120 minutes. Vancomycin-treated tendon tissue showed no significant increase in apoptotic gene expression, or apoptotic protein levels in tissue or supernatant, ex vivo. Vancomycin was associated with a reduction in inflammatory proteins from treated tendon supernatants (IL-6; P < .05). CONCLUSION: Vancomycin did not significantly alter the molecular structure of the hamstring graft. Reductions in matrix protein and inflammatory cytokine release point to a potential beneficial effect of vancomycin in generating a homeostatic environment. CLINICAL RELEVANCE: Vancomycin ACL wrap does not alter the molecular structure of the ACL hamstring graft and may improve graft integrity.

30-day outcomes in hip fracture patients during the COVID-19 pandemic compared to the preceding year.

AIMS: To establish if COVID-19 has worsened outcomes in patients with AO 31 A or B type hip fractures. METHODS: Retrospective analysis of prospectively collected data was performed for a five-week period from 20 March 2020 and the same time period in 2019. The primary outcome was mortality at 30 days. Secondary outcomes were COVID-19 infection, perioperative pulmonary complications, time to theatre, type of anaesthesia, operation, grade of surgeon, fracture type, postoperative intensive care admission, venous thromboembolism, dislocation, infection rates, and length of stay. RESULTS: In all, 76 patients with hip fractures were identified in each group. All patients had 30-day follow-up. There was no difference in age, sex, American Society of Anesthesiologists (ASA) classification or residence at time of injury. However, three in each group were not fit for surgery. No significant difference was found in 30-day mortality; ten patients (13%) in 2019 and 11 patients (14%) in 2020 (p = 0.341). In the 2020 cohort, ten patients tested positive for COVID-19, two (20%) of whom died. There was no significant increase in postoperative pulmonary complications. Median time to theatre was 20 hours (interquartile range (IQR) 16 to 25) in 2019 versus 23 hours (IQR 18 to 30) in 2020 (p = 0.130). Regional anaesthesia increased from 24 (33%) cases in 2019 to 46 (63%) cases in 2020, but ten (14%) required conversion to general anaesthesia. In both groups, 53 (70%) operations were done by trainees. Hemiarthroplasty for 31 B type fractures was the most common operation. No significant difference was found for intensive care admission or 30-day venous thromboembolism, dislocation or infection, or length of stay. CONCLUSION: Little information exists on mortality and complications after hip fracture during the COVID-19 pandemic. At the time of writing, no other study of outcomes in the UK has been published.Cite this article: Bone Joint Open 2020;1-7:415-419.

S100A8 & S100A9: Alarmin mediated inflammation in tendinopathy.

Alarmins S100A8 and S100A9 are endogenous molecules released in response to environmental triggers and cellular damage. They are constitutively expressed in immune cells such as monocytes and neutrophils and their expression is upregulated under inflammatory conditions. The molecular mechanisms that regulate inflammatory pathways in tendinopathy are largely unknown therefore identifying early immune effectors is essential to understanding the pathology. Based on our previous investigations highlighting tendinopathy as an alarmin mediated pathology we sought evidence of S100A8 & A9 expression in a human model of tendinopathy and thereafter, to explore mechanisms whereby S100 proteins may regulate release of inflammatory mediators and matrix synthesis in human tenocytes. Immunohistochemistry and quantitative RT-PCR showed S100A8 & A9 expression was significantly upregulated in tendinopathic tissue compared with control. Furthermore, treating primary human tenocytes with exogenous S100A8 & A9 significantly increased protein release of IL-6, IL-8, CCL2, CCL20 and CXCL10; however, no alterations in genes associated with matrix remodelling were observed at a transcript level. We propose S100A8 & A9 participate in early pathology by modulating the stromal microenvironment and influencing the inflammatory profile observed in tendinopathy. S100A8 and S100A9 may participate in a positive feedback mechanism involving enhanced leukocyte recruitment and release of pro-inflammatory cytokines from tenocytes that perpetuates the inflammatory response within the tendon in the early stages of disease.

Unusual complication of a tattoo in an immunosuppressed patient.

Tattooing for decorative body art is becoming more popular and, as a result, so are tattoo-related complications. Patients are unlikely to discuss tattoos with medical professionals, even though these might be relevant. Long-term immunosuppressed patients are often young adults who may wish to consider tattooing. It is well recognised that immunosuppressed patients are at increased risk of infection including cutaneous mycobacterial infections. They therefore represent a group that is at a potentially higher risk of tattoo-related complications and warrant special consideration.We present the first documented case of inflammatory myopathy as a complication following tattooing in an immunosuppressed individual. This unusual case presented as distal thigh and medial knee pain and it was only after some time that a link to the tattoo was made. This serves as a reminder to consider tattoo-related complications in the differential diagnosis of unusual atraumatic musculoskeletal pain, especially in immunosuppressed individuals.

IL-17A mediates inflammatory and tissue remodelling events in early human tendinopathy.

Increasingly, inflammatory mediators are considered crucial to the onset and perpetuation of tendinopathy. We sought evidence of interleukin 17A (IL-17A) expression in early human tendinopathy and thereafter, explored mechanisms whereby IL-17A mediated inflammation and tissue remodeling in human tenocytes. Torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing 'early pathology') along with control biopsies were collected from patients undergoing shoulder surgery. Markers of inflammation and IL-17A were quantified by RT-PCR and immunohistochemistry. Human tendon cells were derived from hamstring tendon obtained during ACL reconstruction. In vitro effects of IL-17A upon tenocytes were measured using RT-PCR, multiplex cytokine assays, apoptotic proteomic profiling, immunohistochemistry and annexin V FACS staining. Increased expression of IL-17A was detected in 'early tendinopathy' compared to both matched samples and non-matched control samples (p < 0.01) by RT-PCR and immunostaining. Double immunofluoresence staining revealed IL-17A expression in leukocyte subsets including mast cells, macrophages and T cells. IL-17A treated tenocytes exhibited increased production of proinflammatory cytokines (p < 0.001), altered matrix regulation (p < 0.01) with increased Collagen type III and increased expression of several apoptosis related factors. We propose IL-17A as an inflammatory mediator within the early tendinopathy processes thus providing novel therapeutic approaches in the management of tendon disorders.

Explaining the non-newtonian character of aggregating monoclonal antibody solutions using small-angle neutron scattering.

A monoclonal antibody solution displays an increase in low shear rate viscosity upon aggregation after prolonged incubation at 40°C. The morphology and interactions leading to the formation of the aggregates responsible for this non-Newtonian character are resolved using small-angle neutron scattering. Our data show a weak repulsive barrier before proteins aggregate reversibly, unless a favorable contact with high binding energy occurs. Two types of aggregates were identified after incubation at 40°C: oligomers with radius of gyration ∼10 nm and fractal submicrometer particles formed by a slow reaction-limited aggregation process, consistent with monomers colliding many times before finding a favorable strong interaction site. Before incubation, these antibody solutions are Newtonian liquids with no increase in low shear rate viscosity and no upturn in scattering at low wavevector, whereas aggregated solutions under the same conditions have both of these features. These results demonstrate that fractal submicrometer particles are responsible for the increase in low shear rate viscosity and low wavevector upturn in scattered intensity of aggregated antibody solutions; both are removed from aggregated samples by filtering.

IL-21 receptor expression in human tendinopathy.

The pathogenetic mechanisms underlying tendinopathy remain unclear, with much debate as to whether inflammation or degradation has the prominent role. Increasing evidence points toward an early inflammatory infiltrate and associated inflammatory cytokine production in human and animal models of tendon disease. The IL-21/IL-21R axis is a proinflammatory cytokine complex that has been associated with chronic inflammatory diseases including rheumatoid arthritis and inflammatory bowel disease. This project aimed to investigate the role and expression of the cytokine/receptor pair IL-21/IL-21R in human tendinopathy. We found significantly elevated expression of IL-21 receptor message and protein in human tendon samples but found no convincing evidence of the presence of IL-21 at message or protein level. The level of expression of IL-21R message/protein in human tenocytes was significantly upregulated by proinflammatory cytokines (TNFα/IL-1ß) in vitro. These findings demonstrate that IL-21R is present in early human tendinopathy mainly expressed by tenocytes and macrophages. Despite a lack of IL-21 expression, these data again suggest that early tendinopathy has an inflammatory/cytokine phenotype, which may provide novel translational targets in the treatment of tendinopathy.

DIY 3D printing of custom orthopaedic implants: a proof of concept study.

3D printing is an emerging technology that is primarily used for aiding the design and prototyping of implants. As this technology has evolved it has now become possible to produce functional and definitive implants manufactured using a 3D printing process. This process, however, previously required a large financial investment in complex machinery and professionals skilled in 3D product design. Our pilot study's aim was to design and create a 3D printed custom orthopaedic implant using only freely available consumer hardware and software.

Does degree of trochlear dysplasia and position of femoral tunnel influence outcome after medial patellofemoral ligament reconstruction?

BACKGROUND: The medial patellofemoral ligament (MPFL) is the main restraining force against lateral patellar displacement. It is disrupted after patellar subluxation or dislocation. Reconstruction of the MPFL is frequently performed when nonoperative management fails and the patient experiences recurrent patellar dislocation. PURPOSE: To determine the relationship between the degree of trochlear dysplasia and femoral tunnel position and outcome after MPFL reconstruction. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 68 patients (72 knees) with recurrent dislocation of the patella underwent MPFL reconstruction. The mean follow-up was 31.3 months (range, 13-72 months). Clinical and functional outcomes were recorded using the Kujala, Lysholm, and Tegner scores. Postoperative complications, participation in sporting activity, and overall patient satisfaction were determined. Radiographs were analyzed to evaluate congruence angle, lateral patellofemoral angle, patellar height, trochlear dysplasia, trochlear boss height, and position of the femoral tunnel. RESULTS: The mean Kujala, Lysholm, and Tegner scores postoperatively were 76.2, 73.8, and 3.6, respectively (n = 61). The mean congruence angle (n = 30) improved from 22.5° to 1.0° postoperatively (P = .000038), the lateral patellofemoral angle (n = 30) improved from 7.4° to 7.8° postoperatively (P = .048), and the patellar height (n = 46) using the Caton-Deschamps method improved from 1.1 to 1.0 postoperatively (P = .000016). Mild trochlear dysplasia grade A/B was found in 89% of patients (n = 54), and 11% of patients (n = 7) had severe grade C/D dysplasia. The mean distance from the anatomic insertion of the MPFL to the center of the tunnel was 9.3 mm (range, 0.5-28.2 mm), with 71.7% thought to be within 10 mm of the anatomic position defined by Schottle (n = 46). When patients with high-grade trochlear dysplasia were excluded, anatomically placed femoral tunnels demonstrated significantly better clinical scores than did tunnels not placed anatomically (Kujala score, P = .028; Lysholm score, P = .012). A multivariate logistic regression analysis also demonstrated that the distance of the femoral tunnel from the anatomic position predicted clinical outcome (Kujala score, P = .043; Lysholm score, P = .028). All of the patients with severe trochlear dysplasia (n = 7) suffered from recurrent dislocations postoperatively, compared with only 9.3% of patients (n = 5) with mild trochlear dysplasia (P = .0001). Four patients had patellar fractures postoperatively. Of patients with mild dysplasia, 83% were either very satisfied or satisfied with the outcome of their surgery compared with only 57% with severe dysplasia (P = .05). Of patients with mild trochlear dysplasia, 56% returned to sport postoperatively compared with only 43% of patients with severe trochlear dysplasia (P = .526). CONCLUSION: This study demonstrates the importance of restoration of the anatomic insertion point of the MPFL when performing MPFL reconstruction and proposes that this procedure should not be performed in isolation in patients with high-grade trochlear dysplasia.

Hypoxia: a critical regulator of early human tendinopathy.

OBJECTIVES: To seek evidence for the role of hypoxia in early human tendinopathy, and thereafter to explore mechanisms whereby tissue hypoxia may regulate apoptosis, inflammatory mediator expression and matrix regulation in human tenocytes. METHODS: Fifteen torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing 'early pathology') biopsies were collected from patients undergoing arthroscopic shoulder surgery. Control samples of the subscapularis tendon were collected from 10 patients undergoing arthroscopic stabilisation surgery. Markers of hypoxia were quantified by immunohistochemical methods. Human tendon-derived primary cells were derived from hamstring tendon tissue obtained during hamstring tendon anterior cruciate ligament reconstruction. The impact of hypoxia upon tenocyte biology ex vivo was measured using quantitative real-time PCR, multiplex cytokine assays, apoptotic proteomic profiling, immunohistochemistry and annexin V fluorescence-activated cell sorter staining. RESULTS: Increased expression of hypoxia-inducible factor 1α, Bcl-2 and clusterin was detected in subscapularis tendon samples compared with both matched torn samples and non-matched control samples (p<0.01). Hypoxic tenocytes exhibited increased production of proinflammatory cytokines (p<0.001), altered matrix regulation (p<0.01) with increased production of collagen type III operating through a mitogen-activated protein kinase-dependent pathway. Finally, hypoxia increased the expression of several mediators of apoptosis and thereby promoted tenocyte apoptosis. CONCLUSION: Hypoxia promotes the expression of proinflammatory cytokines, key apoptotic mediators and drives matrix component synthesis towards a collagen type III profile by human tenocytes. The authors propose hypoxic cell injury as a critical pathophysiological mechanism in early tendinopathy offering novel therapeutic opportunities in the management of tendon disorders.

Participation in sporting activities following knee replacement: total versus unicompartmental.

Few studies have been published assessing patients sporting activity after total knee arthroplasty (TKA) and unicompartmental knee arthroplasty (UKA). Common concerns of patients undergoing TKA or UKA are whether they can continue with sporting activities after surgery. This study compares the sporting activity of TKA and UKA patients preoperatively and postoperatively. A total of 110 patients were surveyed by questionnaire. Seventy-six patients had undergone TKA and 34 patients had undergone UKA. They were assessed for their participation in low-impact sport preoperatively and postoperatively at a mean follow up of 21.6 +/- 5.3 and 22.3 +/- 7.8 months, respectively. Low-impact sports are those which a surgeon would expect patients to be able to participate in postoperatively. Data were separately analysed for older and younger patients and women and men, respectively. The results were as follows: before surgery, 55 of 76 patients in the TKA group participated in an average of 1.3 different sports and postoperatively, 35 of 76 patients participated in an average of 0.7 different sports. In the UKA group, 30 of 34 patients participated in an average of 1.5 different sports preoperatively and postoperatively, 29 of 34 patients participated in an average of 1.4 different sports. The return to sport rate was 96.7% in the UKA group and 63.6% in the TKA group. In the TKA group, the average frequency of sport preoperatively was 3.0 sessions per week (62.7 min) and postoperatively it decreased to 2.0 sessions per week (37.5 minutes). In the UKA group, the average frequency of sport preoperatively was 3.2 sessions per week (85.0 min) and postoperatively it increased to 3.4 sessions per week (92.1 min). The average time before resuming sport after surgery was 4.1 months in the TKA group and 3.6 months in the UKA group; 42.9% of patients in the TKA group and 24.1% of patients in the UKA group reported pain during sports after surgery; 80.3% of the patients in the TKA group and 88.2% of the patients in the UKA group felt that surgery had increased or maintained their sporting ability. Oxford knee scores decreased significantly one year after surgery in both the TKA group and the UKA group. In conclusion, the patients in our study had a significantly greater return to sport rate after UKA than patients who had undergone TKA. A large proportion of patients in the TKA group did not return to sport which their surgeon would have expected them to including golf and bowls. Patients in the UKA group also took part in more sporting sessions and for a longer period of time than patients in the TKA group. Moreover, patients undergoing UKA also returned to sport more quickly than patients undergoing TKA.

Structural characterization of a mutated, ADCC-enhanced human Fc fragment.

We report here the three-dimensional structure of a human Fc fragment engineered for enhanced antibody dependent cell mediated cytotoxicity (ADCC). The triple mutation S239D/A330L/I332E ('3M') was introduced into the C(H)2 portion of a human immunoglobulin G1 (IgG1) Fc. These three substitutions typically result in an about 10-100-fold increase in human IgG1 binding to human Fc gamma RIIIA (CD16). The recombinantly produced Fc/3M fragment was crystallized and its structure solved at a resolution of 2.5A using molecular replacement. No dramatic structural changes were observed in Fc/3M when compared with unmutated human Fc fragments. However, we found that the relative positions of its C(H)2 domains allowed for an unusually 'open' conformation of the entire fragment. Although this particular structural feature could be due to crystallization artifacts or intrinsic variability, we propose that molecular mechanisms at the basis of the enhanced interaction between Fc/3M and CD16 could include enhanced Fc openness as well as the introduction of additional hydrophobic contacts, hydrogen bonds and/or electrostatic interactions at the corresponding interface. The existence of a more pronounced cleft between the two Fc chains as well as of repulsive, electrostatic intra-chain interactions may also account in part for the decreased thermostability of both Fc/3M and a 3M-modified humanized anti-human EphA2 IgG1 when compared with their respective unmutated counterparts.

Tibial shaft fractures in football players.

BACKGROUND: Football is officially the most popular sport in the world. In the UK, 10% of the adult population play football at least once a year. Despite this, there are few papers in the literature on tibial diaphyseal fractures in this sporting group. In addition, conflicting views on the nature of this injury exist. The purpose of this paper is to compare our experience of tibial shaft football fractures with the little available literature and identify any similarities and differences. METHODS AND RESULTS: A retrospective study of all tibial football fractures that presented to a teaching hospital was undertaken over a 5 year period from 1997 to 2001. There were 244 tibial fractures treated. 24 (9.8%) of these were football related. All patients were male with a mean age of 23 years (range 15 to 29) and shin guards were worn in 95.8% of cases. 11/24 (45.8%) were treated conservatively, 11/24 (45.8%) by Grosse Kemp intramedullary nail and 2/24 (8.3%) with plating. A difference in union times was noted, conservative 19 weeks compared to operative group 23.9 weeks (p < 0.05). Return to activity was also different in the two groups, conservative 27.6 weeks versus operative 23.3 weeks (p < 0.05). The most common fracture pattern was AO Type 42A3 in 14/24 (58.3%). A high number 19/24 (79.2%) were simple transverse or short oblique fractures. There was a low non-union rate 1/24 (4.2%) and absence of any open injury in our series. CONCLUSION: Our series compared similarly with the few reports available in the literature. However, a striking finding noted by the authors was a drop in the incidence of tibial shaft football fractures. It is likely that this is a reflection of recent compulsory FIFA regulations on shinguards as well as improvements in the design over the past decade since its introduction.

Theories about consensus-based conservation.

"Conservation and the Myth of Consensus" (Peterson et al. 2005) levels several serious indictments against consensus-based approaches to environmental decision making. Namely, the authors argue that consensus processes (1) reinforce apathy and ignorance of conservation issues; (2) legitimize damage to the environment; (3) quash public debate about conservation; (4) solidify the existing balance of power in favor of prodevelopment forces; and (5) block progress toward an ecologically sustainable future. Careful scrutiny of consensus-based approaches is important, especially considering their surging use in conservation policy. In the spirit of advancing the debate further, I review some of the limitations of the essay and its modes of inquiry.