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

Two-stage revision for prosthetic joint infection: predictors of outcome and the role of reimplantation microbiology

We describe rates of success for two-stage revision of prosthetic joint infection (PJI), including data on reimplantation microbiology. Methods: We retrospectively collected data from all the cases of PJI that were managed with two-stage revision over a 4 year period. Patients were managed with an antibiotic-free period before reimplantation, in order to confirm, clinically and microbiologically, that infection was successfully treated. Results: One hundred and fifty-two cases were identified. The overall success rate (i.e. retention of the prosthesis over 5.75 years of follow-up) was 83%, but was 89 % for first revisions and 73 % for re-revisions [hazard ratio2.9, 95 % confidence interval (CI) 1.2–7.4, P0.023]. Reimplantation microbiology was frequently positive (14%), but did not predict outcome (hazard ratio1.3, 95 % CI 0.4–3.7, P0.6). Furthermore, most unplanned debridements following the first stage were carried out before antibiotics were stopped (25 versus 2 debridements). Conclusions: We did not identify evidence supporting the use of an antibiotic-free period before reimplantation and routine reimplantation microbiology. Re-revision was associated with a significantly worse outcome

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

One hundred and twelve infected arthroplasties treated with ‘DAIR’ (debridement, antibiotics and implant retention): antibiotic duration and outcome

OBJECTIVES: We describe treatment failure rates by antibiotic duration for prosthetic joint infection (PJI) managed with debridement, antibiotics and implant retention (DAIR). METHODS: We retrospectively collected data from all the cases of PJI that were managed with DAIR over a 5 year period. Surgical debridement, microbiological sampling, early intravenous antibiotics and prolonged oral follow-on antibiotics were used. RESULTS: One hundred and twelve cases of PJI were identified. Twenty infections (18%) recurred during a mean follow-up of 2.3 years. The mean duration of antibiotic use was 1.5 years. Failure was more common after arthroscopic debridement, for previously revised joints and for Staphylococcus aureus infection. There were 12 failures after stopping antibiotics and 8 while on antibiotics [hazard ratio (HR) = 4.3, 95% confidence interval (CI) 1.4-12.8, P = 0.01]. However, during the first 3 months of follow-up, there were eight failures after stopping antibiotics and two while on antibiotics (HR = 7.0, 95% CI 1.5-33, P = 0.015). The duration of antibiotic therapy prior to stopping did not predict outcome. CONCLUSIONS: PJI may be managed by DAIR. The risk of failure with this strategy rises after stopping oral antibiotics, but lengthening antibiotic therapy may simply postpone, rather than prevent, failure

‘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

Malignant melanoma and bone resorption

The cellular and humoral mechanisms accounting for osteolysis in skeletal metastases of malignant melanoma are uncertain. Osteoclasts, the specialised multinucleated cells that carry out bone resorption, are derived from monocyte/macrophage precursors. We isolated tumour-associated macrophages (TAMs) from metastatic (lymph node/skin) melanomas and cultured them in the presence and absence of osteoclastogenic cytokines and growth factors. The effect of tumour-derived fibroblasts and melanoma cells on osteoclast formation and resorption was also analysed. Melanoma TAMs (CD14+/CD51−) differentiated into osteoclasts (CD14−/CD51+) in the presence of receptor activator for nuclear factor κB ligand (RANKL) and macrophage-colony stimulating factor. Tumour-associated macrophage-osteoclast differentiation also occurred via a RANKL-independent pathway when TAMs were cultured with tumour necrosis factor-α and interleukin (IL)-1α. RT–PCR showed that fibroblasts isolated from metastatic melanomas expressed RANKL messenger RNA and the conditioned medium of cultured melanoma fibroblasts was found to be capable of inducing osteoclast formation in the absence of RANKL; this effect was inhibited by the addition of osteoprotegerin (OPG). We also found that cultured human SK-Mel-29 melanoma cells produce a soluble factor that induces osteoclast differentiation; this effect was not inhibited by OPG. Our findings indicate that TAMs in metastatic melanomas can differentiate into osteoclasts and that melanoma fibroblasts and melanoma tumour cells can induce osteoclast formation by RANKL-dependent and RANKL-independent mechanisms, respectively

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