Analysis of margin classification systems for assessing the risk of local recurrence after soft tissue sarcoma resection

Purpose: To compare the ability of margin classification systems to determine local recurrence (LR) risk after soft tissue sarcoma (STS) resection. Methods: Two thousand two hundred seventeen patients with nonmetastatic extremity and truncal STS treated with surgical resection and multidisciplinary consideration of perioperative radiotherapy were retrospectively reviewed. Margins were coded by residual tumor (R) classification (in which microscopic tumor at inked margin defines R1), the R+1mm classification (in which microscopic tumor within 1 mm of ink defines R1), and the Toronto Margin Context Classification (TMCC; in which positive margins are separated into planned close but positive at critical structures, positive after whoops re-excision, and inadvertent positive margins). Multivariate competing risk regression models were created. Results: By R classification, LR rates at 10-year follow-up were 8%, 21%, and 44% in R0, R1, and R2, respectively. R+1mm classification resulted in increased R1 margins (726 v 278, P < .001), but led to decreased LR for R1 margins without changing R0 LR; for R0, the 10-year LR rate was 8% (range, 7% to 10%); for R1, the 10-year LR rate was 12% (10% to 15%) . The TMCC also showed various LR rates among its tiers (P < .001). LR rates for positive margins on critical structures were not different from R0 at 10 years (11% v 8%, P = .18), whereas inadvertent positive margins had high LR (5-year, 28% [95% CI, 19% to 37%]; 10-year, 35% [95% CI, 25% to 46%]; P < .001). Conclusion: The R classification identified three distinct risk levels for LR in STS. An R+1mm classification reduced LR differences between R1 and R0, suggesting that a negative but < 1-mm margin may be adequate with multidisciplinary treatment. The TMCC provides additional stratification of positive margins that may aid in surgical planning and patient education

Nigellissima: A Study of Glamour, Performativity and Embodiment

This is a study of glamour, its complexities and its relationship with and role within celebrity culture. We explore glamour in the context of Nigella, the London-born TV cook, food writer and self-proclaimed ‘domestic goddess’ of British culinary culture. In our study we consider the interconnections between glamour, specifically Italian-style retro-glamour, and performativity in Nigella’s career. We also address the role of embodiment and authenticity in the masquerade of femininity. Our analysis focuses on Nigella’s glamour over time, considering its creation, enactment and reaffirmation following scandal. We conclude by speculating on glamour’s complex and ambivalent relationship with celebrity culture, and the role of vulnerability in creating authentic and enduring glamour in contemporary consumer society

Assessment of Objective Ambulation in Lower Extremity Sarcoma Patients with a Continuous Activity Monitor: Rationale and Validation

In addition to patient reported outcome measures, accelerometers may provide useful information on the outcome of sarcoma patients treated with limb salvage. The StepWatch (SW) Activity Monitor (SAM) is a two-dimensional accelerometer worn on the ankle that records an objective measure of walking performance. The purpose of this study was to validate the SW in a cross-sectional population of adult patients with lower extremity sarcoma treated with limb salvage. The main outcome was correlation of total steps with the Toronto Extremity Salvage Score (TESS). In a sample of 29 patients, a mean of 12 days of SW data was collected per patient (range 6–16), with 2767 average total steps (S.D. 1867; range 406–7437). There was a moderate positive correlation between total steps and TESS (r=0.56,  P=0.002). Patients with osseous tumors walked significantly less than those with soft tissue sarcoma (1882 versus 3715, P<0.01). This study supports the validity of the SAM as an activity monitor for the objective assessment of real world physical function in sarcoma patients

Unique trancriptome signatures and GM-CSF expression in lymphocytes from patients with spondyloarthritis

Spondyloarthritis encompasses a group of common inflammatory diseases thought to be driven by IL-17A-secreting type-17 lymphocytes. Here we show increased numbers of GM-CSFproducing CD4 and CD8 lymphocytes in the blood and joints of patients with spondyloarthritis, and increased numbers of IL-17A+ GM-CSF+ double-producing CD4, CD8, γδ and NK cells. GM-CSF production in CD4 T cells occurs both independently and in combination with classical Th1 and Th17 cytokines. Type 3 innate lymphoid cells producing predominantly GM-CSF are expanded in synovial tissues from patients with spondyloarthritis. GM-CSF+ CD4+ cells, isolated using a triple cytokine capture approach, have a specific transcriptional signature. Both GMCSF+ and IL-17A+ GM-CSF+ double-producing CD4 T cells express increased levels of GPR65, a proton-sensing receptor associated with spondyloarthritis in genome-wide association studies and pathogenicity in murine inflammatory disease models. Silencing GPR65 in primary CD4 T cells reduces GM-CSF production. GM-CSF and GPR65 may thus serve as targets for therapeutic intervention of spondyloarthritis

‘We are not calling her Italian’: narratives and images of ethnic incorporation in Isa Miranda’s American persona.

This article discusses the impact of Hollywood standards of homogenisation on Isa Miranda’s cosmopolitan appeal during her work for Paramount. The article suggests that Miranda’s American image was constructed in an attempt to establish her as a Marlene Dietrich type in order to defuse the potential threat represented by her ethnic Otherness; meanwhile, the Italian actress was framed within film narratives that played out (albeit indirectly) an idealised conception of successful American assimilation of European immigrants. In the process, Miranda was visually constructed through images that effectively ‘whitened’ her, and her Italianness was thus displaced onto an ideal of Northern European whiteness that bespoke a desire to reassert whiteness as the norm in 1930s America

Niccolo Machiavelli, cultural intermediaries and the category of achieved celebrity

The escalating interest in celebrity studies has not translated into a serious enquiry into the origins of the subject in social and political theory. Instead, celebrity has been usually explained as either the reflection of industrialisation or the expression of timeless, unchanging fate. The result is a distorted, compressed time frame in which the phenomenon is located in unsatisfactory, metaphysical accounts of the position of celebrity in the social order. This paper aims to redress the balance by demonstrating the profound importance of cultural intermediaries in the social construction of celebrity. I argue that the birth of cultural intermediaries lies in Florentine civic humanism. Machiavelli’s The Prince has been celebrated as a major contribution to the acquisition and effective management of tyrannical power. There is ample reason to hold this view. At the same time, this interpretation is too limiting. When read from the standpoint of the rise of Florentine civic humanism, the text is also, transparently, a contribution to the successful engineering of renown. More particularly, in this respect, it offers a prototypical understanding of cultural intermediaries. As such, this paper contends that Machiavelli’s study is a seminal contribution to the study of celebrity. Machiavelli formulates impersonal principles on exposure management and the accumulation of attention capital that are presented as the preserve of civil experts. Far from being the high-water mark of tyrannical power, The Prince is evidence of the growth of civic humanism and the ascending importance of expertise in managing fame. The paper aims to revise the boundaries of celebrity studies by demonstrating the canonical significance of Machiavelli’s text. Further, it proposes that cultural intermediaries are seminal in the emergence and development of the fame economy

Oral versus intravenous antibiotics for bone and joint infections: the OVIVA non-inferiority RCT

Background Management of bone and joint infection commonly includes 4–6 weeks of intravenous (IV) antibiotics, but there is little evidence to suggest that oral (PO) therapy results in worse outcomes. Objective To determine whether or not PO antibiotics are non-inferior to IV antibiotics in treating bone and joint infection. Design Parallel-group, randomised (1 : 1), open-label, non-inferiority trial. The non-inferiority margin was 7.5%. Setting Twenty-six NHS hospitals. Participants Adults with a clinical diagnosis of bone, joint or orthopaedic metalware-associated infection who would ordinarily receive at least 6 weeks of antibiotics, and who had received ≤ 7 days of IV therapy from definitive surgery (or start of planned curative treatment in patients managed non-operatively). Interventions Participants were centrally computer-randomised to PO or IV antibiotics to complete the first 6 weeks of therapy. Follow-on PO therapy was permitted in either arm. Main outcome measure The primary outcome was the proportion of participants experiencing treatment failure within 1 year. An associated cost-effectiveness evaluation assessed health resource use and quality-of-life data. Results Out of 1054 participants (527 in each arm), end-point data were available for 1015 (96.30%) participants. Treatment failure was identified in 141 out of 1015 (13.89%) participants: 74 out of 506 (14.62%) and 67 out of 509 (13.16%) of those participants randomised to IV and PO therapy, respectively. In the intention-to-treat analysis, using multiple imputation to include all participants, the imputed risk difference between PO and IV therapy for definitive treatment failure was –1.38% (90% confidence interval –4.94% to 2.19%), thus meeting the non-inferiority criterion. A complete-case analysis, a per-protocol analysis and sensitivity analyses for missing data each confirmed this result. With the exception of IV catheter complications [49/523 (9.37%) in the IV arm vs. 5/523 (0.96%) in the PO arm)], there was no significant difference between the two arms in the incidence of serious adverse events. PO therapy was highly cost-effective, yielding a saving of £2740 per patient without any significant difference in quality-adjusted life-years between the two arms of the trial. Limitations The OVIVA (Oral Versus IntraVenous Antibiotics) trial was an open-label trial, but bias was limited by assessing all potential end points by a blinded adjudication committee. The population was heterogenous, which facilitated generalisability but limited the statistical power of subgroup analyses. Participants were only followed up for 1 year so differences in late recurrence cannot be excluded. Conclusions PO antibiotic therapy is non-inferior to IV therapy when used during the first 6 weeks in the treatment for bone and joint infection, as assessed by definitive treatment failure within 1 year of randomisation. These findings challenge the current standard of care and provide an opportunity to realise significant benefits for patients, antimicrobial stewardship and the health economy. Future work Further work is required to define the optimal total duration of therapy for bone and joint infection in the context of specific surgical interventions. Currently, wide variation in clinical practice suggests significant redundancy that likely contributes to the excess and unnecessary use of antibiotics. Trial registration Current Controlled Trials ISRCTN91566927. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 38. See the NIHR Journals Library website for further project information

Oral versus intravenous antibiotics for bone and joint infection

BACKGROUND The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication. METHODS We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points. RESULTS Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of −1.4 percentage points (90% confidence interval [CI], −4.9 to 2.2; 95% CI, −5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P=0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%). CONCLUSIONS Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927.