Antibiotic Therapy for 6 or 12 Weeks for Prosthetic Joint Infection.

BACKGROUND: The management of prosthetic joint infection usually consists of a combination of surgery and antimicrobial therapy. The appropriate duration of antimicrobial therapy for this indication remains unclear. METHODS: We performed an open-label, randomized, controlled, noninferiority trial to compare 6 weeks with 12 weeks of antibiotic therapy in patients with microbiologically confirmed prosthetic joint infection that had been managed with an appropriate surgical procedure. The primary outcome was persistent infection (defined as the persistence or recurrence of infection with the initial causative bacteria, with an antibiotic susceptibility pattern that was phenotypically indistinguishable from that at enrollment) within 2 years after the completion of antibiotic therapy. Noninferiority of 6 weeks of therapy to 12 weeks of therapy would be shown if the upper boundary of the 95% confidence interval for the absolute between-group difference (the value in the 6-week group minus the value in the 12-week group) in the percentage of patients with persistent infection within 2 years was not greater than 10 percentage points. RESULTS: A total of 410 patients from 28 French centers were randomly assigned to receive antibiotic therapy for 6 weeks (205 patients) or for 12 weeks (205 patients). Six patients who withdrew consent were not included in the analysis. In the main analysis, 20 patients who died during follow-up were excluded, and missing outcomes for 6 patients who were lost to follow-up were considered to be persistent infection. Persistent infection occurred in 35 of 193 patients (18.1%) in the 6-week group and in 18 of 191 patients (9.4%) in the 12-week group (risk difference, 8.7 percentage points; 95% confidence interval, 1.8 to 15.6); thus, noninferiority was not shown. Noninferiority was also not shown in the per-protocol and sensitivity analyses. We found no evidence of between-group differences in the percentage of patients with treatment failure due to a new infection, probable treatment failure, or serious adverse events. CONCLUSIONS: Among patients with microbiologically confirmed prosthetic joint infections that were managed with standard surgical procedures, antibiotic therapy for 6 weeks was not shown to be noninferior to antibiotic therapy for 12 weeks and resulted in a higher percentage of patients with unfavorable outcomes. (Funded by Programme Hospitalier de Recherche Clinique, French Ministry of Health; DATIPO ClinicalTrials.gov number, NCT01816009.).

Large increase of vertebral osteomyelitis in France: a 2010-2019 cross-sectional study.

Vertebral osteomyelitis (VO) represents 4-10% of bone and joint infections. In Western countries, its incidence seems to increase, simultaneously with an increasing number of comorbidities among an ageing population. This study aimed to assess the evolution of VO epidemiology in France over the 2010-2019 decade. A nationwide cross-sectional study was conducted using the French hospital discharge data collected through the French diagnosis-related groups 'Programme de Médicalisation des Systèmes d'Information'. VOs were detected with a previously validated case definition using International Classification of Diseases 10 (ICD-10) codes, implemented with the French current procedural terminology codes. The study population included all patients hospitalised in France during the 2010-2019 decade, aged 15 years old and more. Patient and hospital stay characteristics and their evolutions were described. During the study period, 42 105 patients were hospitalised for VO in France involving 60 878 hospital stays. The mean VO incidence was 7.8/100 000 over the study period, increasing from 6.1/100 000 in 2010 to 11.3/100 000 in 2019. The mean age was 64.8 years old and the sex ratio was 1.56. There were 31 341 (74.4%) patients with at least one comorbidity and 3059 (7.3%) deceased during their hospital stay. Even if rare, device-associated VOs (4450 hospital stays, 7.3%) highly increased over the period. The reliability of the method, based upon an exhaustive database and a validated case definition, provided an effective tool to compare data over time in real-life conditions to regularly update the epidemiology of VO.

Sarcomas in patients over 90: Natural history and treatment-A nationwide study over 6 years.

Soft tissue sarcomas (STS) are rare tumors accounting for less than 1% of human cancers. While the highest incidence of sarcomas is observed in elderly, this population is often excluded or poorly represented in clinical trials. The present study reports on clinicopathological presentation, and outcome of sarcoma patients over 90 recorded in the Netsarc.org French national database. NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor board (MDTB), funded by the French National Cancer Institute to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB, second pathological review, and collection of sarcoma patient characteristics and follow-up are collected in a database Information of patients registered from January 1, 2010, to December 31, 2016, in NETSARC were collected, analyzed and compared to the younger population. Patients with sarcomas aged >90 have almost exclusively sarcomas with complex genomics (92.0% vs. 66.3%), are less frequently metastatic (5.3% vs. 14·7%) at diagnosis, have more often superficial tumors (39.8% vs. 14.7%), as well as limbs and head and neck sites (75.2% vs. 38.7%) (all p < 0.001). Optimal diagnostic procedures and surgery were less frequently performed in patients over 90 (p < 0.001). These patients were less frequently operated in NETSARC centers, as compared to those of younger age groups including aged 80-90. However, local relapse-free survival, metastatic relapse-free survival and relapse-free survival were not significantly different from those of younger patients, in the whole cohort, as well as in the subgroup of operated patients. As expected overall survival was worse in patients over 90 (p < 0.001). Patients over 90 who were not operated had worse overall survival than younger patients (9.9 vs. 27.3 months, p < 0.001). Patients with STS diagnosed after 90 have distinct clinicopathological features, but comparable relapse-free survival, unless clinical practice guidelines recommendations are not applied. Standard management should be proposed to these patients if oncogeriatric status allows.

Watch and Wait Approach for Re-excision After Unplanned Yet Macroscopically Complete Excision of Extremity and Superficial Truncal Soft Tissue Sarcoma is Safe and Does Not Affect Metastatic Risk or Amputation Rate.

BACKGROUND: The benefits of systematic re-excision (RE) after initial unplanned excision (UE) of soft tissue sarcoma (STS) are unknown. OBJECTIVE: The aim of this study was to evaluate the impact of delayed RE versus systematic RE after UE on overall survival (OS), metastatic relapse-free survival (MRFS), local relapse-free survival (LRFS), and rate of amputation. METHODS: Patients who underwent complete UE, without metastasis or residual disease, for primary extremity or superficial STS between 2007 and 2013 were analyzed. The amputation rate, LRFS, MRFS, and OS were assessed in cases of systematic RE in sarcoma referral centers (Group A), systematic RE outside of community centers (Group B), or without RE (Group C). RESULTS: Groups A, B, and C included 300 (48.2%), 71 (11.4%), and 251 (40.4%) patients, respectively. Median follow-up was 61 months and 5-year OS was 88.4%, 87.3%, and 88% in Groups A, B, and C, respectively (p = 0.22), while 5-year MFRS was 85.4%, 86.2%, and 84.9%, respectively (p = 0.938); RE (p = 0.55) did not influence MRFS. The 5-year LRFS was 83%, 73.5%, and 63.8% in Groups A, B and C, respectively (p = 0.00001). Of the 123 local recurrences observed, 0/28, 1/15, and 5/80 patients in Groups A, B, and C, respectively, required amputation (p = 0.41). Factors influencing LRFS were adjuvant radiotherapy [hazard ratio (HR) 0.21; p = 0.0001], initial R0 resection (HR 0.24, p = 0.0001), and Group A (HR 0.44; p = 0.01). CONCLUSION: Systematic RE in sarcoma centers offers best local control but does not impact OS. Delayed RE at the time of local relapse, if any, could be an option.

Biomarkers of bone healing induced by a regenerative approach based on expanded bone marrow-derived mesenchymal stromal cells.

BACKGROUND: Safety and feasibility of a regenerative strategy based on the use of culture-expanded mesenchymal stromal cells (MSCs) have been investigated in phase 2 trials for the treatment of nonunion and osteonecrosis of the femoral head (ONFH). As part of the clinical study, we aimed to evaluate if bone turnover markers (BTMs) could be useful for predicting the regenerative ability of the cell therapy product. MATERIALS AND METHODS: The bone defects of 39 patients (nonunion: n = 26; ONFH: n = 13) were treated with bone marrow-derived MSCs, expanded using a clinical-grade protocol and combined with biphasic calcium phosphate before implantation. Bone formation markers, bone-resorption markers and osteoclast regulatory proteins were measured before treatment (baseline) and after 12 and 24 weeks from surgery. At the same time-points, clinical and radiological controls were performed to evaluate the bone-healing progression. RESULTS: We found that C-Propeptide of Type I Procollagen (CICP) and C-terminal telopeptide of type-I collagen (CTX) varied significantly, not only over time, but also according to clinical results. In patients with a good outcome, CICP increased and CTX decreased, and this trend was observed in both nonunion and ONFH. Moreover, collagen biomarkers were able to discriminate healed patients from non-responsive patients with a good diagnostic accuracy. DISCUSSION: CICP and CTX could be valuable biomarkers for monitoring and predicting the regenerative ability of cell products used to stimulate the repair of refractory bone diseases. To be translated in a clinical setting, these results are under validation in a currently ongoing phase 3 clinical trial.

Distal extremities soft tissue sarcomas: Are they so different from other limb localizations?

BACKGROUND AND OBJECTIVES: Soft tissue sarcoma localization in distal extremities (DESTS) of the limbs (hand/fingers, and foot/toes) is unusual. The literature is scarce about their behavior and this study was designed to assess their epidemiological characteristics, outcomes, and prognosis compared to other limb localizations (OLSTS). METHODS: From 1980 to 2010, adult DESTS and OLSTS in 22 centers were included. Demographics, tumor type, treatment modalities, and latest follow-up status were collected. Primary endpoints were overall survival and local/metastatic recurrence incidences. RESULTS: Two hundred five DESTS and 3001 OLSTS were included. The patients were younger, with more female and smaller tumors in DESTS. There were more clear cell/epithelioid sarcomas, synovial sarcomas, and myxoid liposarcomas vs more dedifferentiated liposarcomas in OLSTS. DESTS tumors were less irradiated and more often amputated (24.3% vs 3.4%). The five-year survival rate was 78.2% compared to 68.6% in OLSTS and after multivariate analysis, STS localization did not impact survival or local/metastatic recurrence. CONCLUSION: Though rare and smaller than other limb localizations, DESTS are to be considered as aggressive. Despite a higher amputation rate, the prognosis remains the same as in OLSTS. Limb sparing vs amputation should be carefully assessed in DESTS, especially if grade 3 or of a poor prognosis histological subtype.

Acute Tibial osteomyelitis caused by intraosseous access during initial resuscitation: a case report and literature review.

BACKGROUND: Intra-osseous (IO) access is recommended in cases of pre-hospital emergency or resuscitation when intravascular (IV) route is difficult or impossible. Despite recent improvement in IO devices and increasing indications, it remains rarely used in practice. Various complications have been reported but are uncommon. CASE PRESENTATION: We report a case of massive acute tibial osteomyelitis in an adult male three months after an IO catheter insertion for emergency drug infusion. We review the literature on association between IO access and acute osteomyelitis in children and adults. CONCLUSIONS: Emergency-care givers and radiologists should be informed about this infrequent complication in order to make early diagnosis and initiate adequate antibiotic therapy.

Comparison of Tumor- and Bone Marrow-Derived Mesenchymal Stromal/Stem Cells from Patients with High-Grade Osteosarcoma.

Osteosarcoma (OS) is suspected to originate from dysfunctional mesenchymal stromal/stem cells (MSC). We sought to identify OS-derived cells (OSDC) with potential cancer stem cell (CSC) properties by comparing OSDC to MSC derived from bone marrow of patients. This study included in vitro characterization with sphere forming assays, differentiation assays, cytogenetic analysis, and in vivo investigations of their tumorigenicity and tumor supportive capacities. Primary cell lines were isolated from nine high-grade OS samples. All primary cell lines demonstrated stromal cell characteristics. Compared to MSC, OSDC presented a higher ability to form sphere clones, indicating a potential CSC phenotype, and were more efficient at differentiation towards osteoblasts. None of the OSDC displayed the complex chromosome rearrangements typical of high grade OS and none of them induced tumors in immunodeficient mice. However, two OSDC demonstrated focused genomic abnormalities. Three out of seven, and six out of seven OSDC showed a supportive role on local tumor development, and on metastatic progression to the lungs, respectively, when co-injected with OS cells in nude mice. The observation of OS-associated stromal cells with rare genetic abnormalities and with the capacity to sustain tumor progression may have implications for future tumor treatments.

CD200 expression in human cultured bone marrow mesenchymal stem cells is induced by pro-osteogenic and pro-inflammatory cues.

Similar to other adult tissue stem/progenitor cells, bone marrow mesenchymal stem/stromal cells (BM MSCs) exhibit heterogeneity at the phenotypic level and in terms of proliferation and differentiation potential. In this study such a heterogeneity was reflected by the CD200 protein. We thus characterized CD200(pos) cells sorted from whole BM MSC cultures and we investigated the molecular mechanisms regulating CD200 expression. After sorting, measurement of lineage markers showed that the osteoblastic genes RUNX2 and DLX5 were up-regulated in CD200(pos) cells compared to CD200(neg) fraction. At the functional level, CD200(pos) cells were prone to mineralize the extra-cellular matrix in vitro after sole addition of phosphates. In addition, osteogenic cues generated by bone morphogenetic protein 4 (BMP4) or BMP7 strongly induced CD200 expression. These data suggest that CD200 expression is related to commitment/differentiation towards the osteoblastic lineage. Immunohistochemistry of trephine bone marrow biopsies further corroborates the osteoblastic fate of CD200(pos) cells. However, when dexamethasone was used to direct osteogenic differentiation in vitro, CD200 was consistently down-regulated. As dexamethasone has anti-inflammatory properties, we assessed the effects of different immunological stimuli on CD200 expression. The pro-inflammatory cytokines interleukin-1ß and tumour necrosis factor-α increased CD200 membrane expression but down-regulated osteoblastic gene expression suggesting an additional regulatory pathway of CD200 expression. Surprisingly, whatever the context, i.e. pro-inflammatory or pro-osteogenic, CD200 expression was down-regulated when nuclear-factor (NF)-κB was inhibited by chemical or adenoviral agents. In conclusion, CD200 expression by cultured BM MSCs can be induced by both osteogenic and pro-inflammatory cytokines through the same pathway: NF-κB.

Orthopaedic implant failure: aseptic implant loosening--the contribution and future challenges of mouse models in translational research.

Aseptic loosening as a result of wear debris is considered to be the main cause of long-term implant failure in orthopaedic surgery and improved biomaterials for bearing surfaces decreases significantly the release of micrometric wear particles. Increasingly, in-depth knowledge of osteoimmunology highlights the role of nanoparticles and ions released from some of these new bearing couples, opening up a new era in the comprehension of aseptic loosening. Mouse models have been essential in the progress made in the early comprehension of pathophysiology and in testing new therapeutic agents for particle-induced osteolysis. However, despite this encouraging progress, there is still no valid clinical alternative to revision surgery. The present review provides an update of the most commonly used bearing couples, the current concepts regarding particle-cell interactions and the approaches used to study the biology of periprosthetic osteolysis. It also discusses the contribution and future challenges of mouse models for successful translation of the preclinical progress into clinical applications.

Regulation and function of immunosuppressive molecule human leukocyte antigen G5 in human bone tissue.

Bone-marrow mesenchymal stem cells (MSCs) are the origin of bone-forming cells with immunomodulation potential. HLA-G5 is among the generated immunosuppressive molecules. HLA-G proteins play a crucial role in promoting the acceptance of allografts. However, the mechanisms regulating the expression of HLA-G5 in human MSCs are unknown. We induced differentiation of MSCs and found that HLA-G5 was greatly up-regulated only in osteoblastic cells (+63% for mRNA). Growth plates and bone callus postfracture in adults showed that only bone-lining cells and mesenchymal progenitors were positive for HLA-G5. Use of gene silencing and dominant-negative factors revealed that HLA-G5 depends on the expression and function of the skeletogenesis master genes RUNX2 and DLX5. In addition, HLA-G5 could directly inhibit osteoclastogenesis by acting on monocytes through SHP1. However, in mature osteoblasts, the expression of HLA-G5 protein was greatly suppressed whereas the proosteoclastogenic factor, RANKL, was concomitantly increased. Down-regulation of HLA-G5 expression during the maturation of osteoblasts was due to binding of the repressor GLI3, a signal transducer of the Hedgehog pathway, to the GLI binding element within the HLA-G promoter. Our findings show that mesenchymal progenitors and osteoblastic cells specifically express HLA-G5 during osteogenesis, with a key role in bone homeostasis.

Percutaneous grafting with bone marrow autologous concentrate for open tibia fractures: analysis of forty three cases and literature review.

PURPOSE: Tibial fractures are the most common lower limb fractures. Some criteria such as open fractures and increasing open stage are known to be associated with high delayed union and pseudarthrosis rate. In cases of delayed or nonunion, classical treatment is autologous cancelous bone graft which is associated with high morbidity rate. The ideal treatment would be a percutaneous harvesting and grafting technique. As bone marrow autologous concentrate (BMAC) presents both advantages, we evaluated this technique from 2002 to 2007. METHODS: This was a retrospective study of 43 cases of open tibial fractures with initial surgical treatment. The criteria of inclusion were open fracture and nonunion, delayed union or suspicion of delayed union. RESULTS: In 23 cases (53.5 %) BMAC was successful. The success group had received significantly more CFU-F than the failure group (469 vs 153.10(3), p = 0.013). A threshold of 360.10(3) CFU-F grafted could be established over which there was 100 % success. BMAC done before 110 days after fracture had 47 % success and BMAC done since 110 days after fracture had 73 % success. BMAC success rate decreased with increasing initial fracture skin open stage. There was no BMAC success in cases of a fracture with a remaining gap of more than 4 mm. We had no complications with the technique at the iliac harvesting zone and tibia injection point. CONCLUSION: BMAC is a technique that should be considered as one of the different alternatives for management of long-bone delayed and nonunion because of its effectiveness, low complication rate, preservation of bone stock and low cost.

Diagnostic value of investigating GNAS mutations in fibro-osseous lesions: a retrospective study of 91 cases of fibrous dysplasia and 40 other fibro-osseous lesions.

GNAS (guanine nucleotide-binding protein/α-subunit) mutations that induce the activation of G-protein α-subunit participate in the pathogenesis of fibrous dysplasia. The aim of this study was to evaluate the sensitivity and specificity of GNAS mutations in fibrous dysplasia and other fibro-osseous lesions, to assess the value of investigating this mutation in the diagnosis of fibro-osseous lesions. We studied 91 cases of fibrous dysplasia. The quality and/or quantity of genomic DNA were suitable for molecular analysis for 51 cases of fibrous dysplasia. GNAS mutations were investigated by three techniques: high-resolution melting (exon 8), allele-specific PCR (exons 8 and 9) and/or direct DNA sequencing (exons 8 and 9). Fibrous dysplasia samples were classified blind to the GNAS mutation status into six histological subtypes as conventional, fibro-involutive, osteosclerosing, cementifying, osteocartilaginous and with prominent aneurysmal cystic changes. We also studied 14 cases of low-grade osteosarcoma, 21 cases of ossifying fibroma, 3 cases of osteofibrous dysplasia, 1 case of osseous dysplasia of the jawbone and 1 post-traumatic lesion of the ribs. Twenty-three cases of fibrous dysplasia (45%) showed mutations of codon 201 (exon 8, p.R201H or p.R201C). No mutation was found on codon 227 (exon 9). GNAS mutations in conventional fibrous dysplasia were detected in the same proportion (47%) as in the other histological subtypes (47%, P=0.96), regardless of sex (P=0.44), age (P=0.90) and location (P=1). GNAS mutations were not detected in any other fibro-osseous lesions. The GNAS mutation was thus specific to fibrous dysplasia in the context of fibro-osseous lesions. The particular mosaicism of mutant and non-mutant cells within the lesion or the existence of other mutations not already described could explain the lack of GNAS mutation in cases of fibrous dysplasia. Investigating this mutation may constitute a valuable complementary diagnostic tool, despite its low sensitivity, particularly in unconventional morphologically different subtypes of fibrous dysplasia.

Comparison of bleeding during trochanteric fracture fixation with mini-invasive or conventional side plate fixation: A randomized controlled trial.

BACKGROUND: Trochanteric fractures are a public health issue due to the aging of the population. Treatment aims to reduce their related morbidity and mortality and to allow an early return to independence. Postoperative anemia is associated with poorer functional recovery and an increased mortality rate. The aim of this study was to assess whether minimally invasive side plate fixation (Minimal Invasive Screw System, MISS™) resulted in reduced perioperative bleeding compared with conventional fixation (Pertrochanteric Hip Screw, PHS™). HYPOTHESIS: We hypothesized that minimally invasive side plate fixation (MISS) would result in reduced perioperative bleeding compared with conventional fixation (PHS). PATIENTS AND METHODS: We conducted an open randomized controlled trial with blinded assessment of the primary outcome. Inclusion criteria were patients aged over 65 years with isolated reducible trochanteric fracture. The 2 surgical implants were of the same shape, the only difference between them being the locking mode of the femoral neck screw on the plate of the MISS device, allowing a percutaneous approach. Primary outcome was perioperative bleeding evaluated with Mercuriali's formula. Secondary outcomes included operating time, scar length, length of hospital stay, radiological criteria such as quality of fracture reduction, implant positioning, bone healing, complications and functional recovery compared between the 2 groups. RESULTS: One hundred and eight patients met the inclusion criteria and were randomized to receive either PHS (n=54) or MISS (n=54). Osteosynthesis with MISS significatively reduced perioperative bleeding (median 243mL, interquartile range [152-410] vs. 334mL [247-430] [p=0.0299]), operating time (65min [57-73] vs. 79min [66-89] [p=0.0002]) and scar length after 45 days (7cm [5-8] vs. 14cm [12-15] [p<0.0001]). There was no statistically significant difference between groups in postoperative complications, revision surgery or serious adverse events. CONCLUSION: Compared with PHS, MISS reduced operating time, perioperative bleeding and scar length with no observed functional difference. LEVEL OF EVIDENCE: I.

Buried de-epithelialized flap: An original solution to fill dead space after sarcoma resection in the thigh. Surgical technique and results of 12 cases.

INTRODUCTION: Soft tissue sarcomas (STS) are often treated with wide excision in combination with adjuvant or neoadjuvant radiotherapy. This is currently the gold standard procedure for the treatment of STS that arise in the extremities. Wound healing complications frequently occur and negatively affect the prognosis. One of the options is to use a buried de-epithelialized flap as it can increase the lymphatic flow, fill the dead space, and cover neurovascular structures and implants. This aim of this retrospective study were two-fold. 1) Describe the surgical technique for this buried de-epithelialized flap after STS removal in the thigh. 2)Evaluate the efficacy of the buried de-epithelialized flap for decreasing wound complications based on a small case series and compare it with previous publications. HYPOTHESIS: We hypothesized that the complication rate of this flap is not higher than the published complication rate for traditional flaps. MATERIALS AND METHODS: Twelve patients (7 women and 5 men) with a mean age of 62±12years (38-76), who underwent surgical removal of an STS in the thigh with coverage by a buried de-epithelialized flap were reviewed at a mean follow-up of 15.8months (range 8-24). RESULTS: Two patients presented with a postoperative wound infection (17%): one superficial and one deep at the surgical site. Neither required an additional plastic surgery procedure. Another patient had a dislocation of their total hip arthroplasty that was managed by closed reduction. One patient died from metastatic progression. There was no skin necrosis of the superficial skin edges, no hematoma or seroma in the other 10 patients. The flap was still visible on cross-sectional imaging at 1 month postoperative with no fluid between the tissue planes or signs of necrosis. The rate of wound healing complications that required surgical treatment was 17% in our case series, versus 16 to 56% in previous publications reporting the results of suture closure only. CONCLUSION: A buried de-epithelialized flap reduces the risk of skin complications by filling dead space, improving lymphatic flow and covering critical structures. It is a reliable and reproducible option after wide local excision of STS in the thigh, with no additional morbidity. LEVEL OF EVIDENCE: IV, retrospective study.

Fully hydroxyapatite-coated distal locking cementless femoral modular implant for revision total hip arthroplasty: A retrospective study of 94 Renaissance™ stems at a minimum 10 years' follow-up.

INTRODUCTION: Modular locking revision total hip arthroplasty femoral implants have been little assessed over the long term. We therefore conducted a retrospective assessment of the Renaissance™ fully hydroxyapatite-coated distal locking cementless femoral modular revision implant at a minimum 10 years' follow-up, analyzing: 1) survivorship, 2) complications, 3) radiologic and functional results, and 4) prevalence of thigh pain. HYPOTHESIS: This implant shows more than 90% 10-year survival. MATERIAL AND METHOD: Between December 2002 and December 2008, 213 implant exchanges were performed in 206 patients, including 97 Renaissance™ stems in 93 patients. Three patients were excluded for missing data. Survival was analyzed for 94 stems in 90 patients at a mean 11.2±3 years' follow-up; radiographic and clinical assessment was performed for 48 stems in 45 patients. The survival criterion was implant fracture and/or femoral stem removal. RESULTS: Survival was 93.5% at 10 years (95% CI: 86-97) and 91.3% at 15 years (95% CI: 82.9-96). Eight stems (8.5%) were exchanged or removed by last follow-up: 5 for infection (5.3%) and 3 for implant breakage (3.2%). The complications rate was 18.1% (N=17, including the 8 stem revisions): 3 stem exchanges for breakage (3.2%), 9 stem infections (9.6%), 3 dislocations (3.2%), and 2 traumatic greater trochanter fractures (2.1%). For the 45 patients with long-term clinical assessment, the mean Postel Merle d'Aubigné and Harris Hip scores were respectively 15±3 and 80 ±19 at last follow-up. Metaphysis reconstruction was satisfactory in 36/48 cases (75.0%). Seven of the 48 stems (14.6%) assessed at longest follow-up, in 45 patients, were causing thigh pain, unrelated to stress-shielding, distal locking screws or metaphyseal filling index. DISCUSSION: The Renaissance™ fully hydroxyapatite-coated modular locking stem with curved nail showed 90% 10-year survival, with satisfactory functional results and little thigh pain. LEVEL OF EVIDENCE: IV; case study without control group.

Management of adipose tumors in the limbs.

Adipose tumors of the limbs are the most common soft tissue lesions and are essentially benign (lipomas). However, in some cases, they can be considered as tumors with intermediate malignancy (atypical lipomatous tumor [ALT]) or sarcoma lineage (liposarcoma [LS]). The essential work-up for a potential adipose tumor consists of a clinical examination and initial ultrasound imaging to determine the size (more or less than 5 cm), the location (over or under the fascia) and any potential atypical vascularization. As needed, MRI will complete the assessment and validate the ultrasound results and confirm the fatty nature of the lesion. Percutaneous biopsy will be done when a deep fatty lesion is larger than 5 cm (long axis), with detection by amplification of the MDM2 gene that guides the diagnosis towards ALT or dedifferentiated LS. Superficial lesions without atypia are not challenging from a surgical point of view. However, large ALT can be more difficult to manage. Their local malignancy does not justify sacrificing any critical structures. As for true LS, their treatment is well defined, with tumor excision addressed at a center belonging to the Network of Sarcomas Reference Centers in France (NETSARC+) and for potential (neo)adjuvant treatment if needed. Inappropriate treatment of a malignant tumor can have serious consequences (loss of chance to survive or to be cured) for the patient. Furthermore, treatment at a specialized cancer center has been proven to be effective as it improves overall survival and reduces local recurrences.

Knee arthrodesis using a compression clamp and a single-plane external fixator to treat infection.

BACKGROUND: In patients with knee infection, arthrodesis by external fixation is a limb-salvage procedure appropriate in highly selected patients. No hardware that might lead to infection is left in situ. However, the fusion rate is limited. Use of a device that applies compression in the coronal plane has been suggested in combination with sagittal external fixation to increase the fusion rate but has not been the focus of published studies. The objectives of this retrospective study were to determine: 1) the fusion rate and, 2) the rate of infection eradication. HYPOTHESIS: Knee arthrodesis using an external fixator and a compression clamp provides higher fusion rates compared to reports of external fixation without compression. MATERIAL AND METHODS: We retrospectively studied 30 patients who underwent knee arthrodesis using external fixation and a compression clamp. The reason for arthrodesis was recurrent infection after total knee arthroplasty in 18 patients and septic arthritis in 12 patients. There were 16 females and 14 males with a mean age of 66.0±11.6 years (range, 30-83 years). Mean follow-up was 42.5±23.6 months (range, 24-106 months). RESULTS: Fusion was achieved in 25 (83%) patients, after a mean of 7.5 months (range, 6-12 months). Of the 8 patients with severe bone loss (≤25% bone contact), 4 experienced non-union, compared to 1 of the 22 patients whose bone loss was moderate or mild (50% and >50% bone contact, respectively) (p=0.01). After at least 2 years of follow-up, the infection was eradicated in 28 (93%) patients. Complications occurred in 9 patients and consisted of pin-site infection managed by lavage (n=3), recurrent infection requiring revision surgery for debridement and lavage combined with material exchange and antibiotic therapy (n=2), and femoral shaft fracture (n=3) or traumatic fracture of the arthrodesis (n=1) treated by changing the clamp and fixator assembly. DISCUSSION: The fusion rate achieved using this combined technique is high and better than obtained with external fixation alone. Our results confirm that infection eradication is obtained more often than with nailing. This one-stage, simple, reproducible procedure does not leave any foreign material in situ. LEVEL OF EVIDENCE: IV, retrospective observational cohort study.

Factors associated with complications after resection of soft tissue sarcomas of the groin.

INTRODUCTION: Soft tissue sarcomas (STS) are rare malignant tumors that require regimented treatment at designated cancer centers. The surgical care of groin tumors is difficult because of frequent local complications. Few studies have been done on prognostic factors and complications. This led us to conduct a retrospective study to: (1) identify factors associated with local postoperative complications during the surgical care of primary groin STS; (2) identify the factors associated with delayed adjuvant radiation therapy; (3) define the optimal surgical treatment strategy to allow adjuvant treatments to start as early as possible, if applicable. HYPOTHESIS: We hypothesized that certain patients presenting with an STS of the groin or inguinal area are at higher risk of complications. MATERIALS AND METHODS: This retrospective single-center study included all the patients admitted to our referral sarcoma center between 1995 and 2016 for the resection of a primary STS of the groin. Major complications were defined as surgical revision, an invasive procedure, or prolonged dressing use. RESULTS: Of the 55 included patients, 13 suffered major complications (24%) of which 10 were surgical revisions, two were repeated aspirations and one was prolonged dressing use. Among the 10 surgical revisions, there were two pedicled salvage flaps. The patients who suffered major complications were significantly more likely to be smokers than the patients who did not have major complications (31% vs 2% (p=0.002)). Obesity and surgical bone exposure were most often associated with complications but not significantly (23% vs 5%, p=0.053 and 38% vs 14% (p=0.057), respectively). Of the 39 patients (71%) who needed postoperative radiation therapy, 5 patients (13%) had it delayed, and 3 patients (8%) did not receive any at all due to major complications. CONCLUSION: In our study, smoking was associated with the occurrence of major complications after groin STS resection and there was a strong trend for obesity and surgical bone exposure. Major complications were associated with a delay in starting postoperative radiation therapy. Thus, we recommend flap coverage after tumor resection in patients who have factors known to contribute to complications. LEVEL OF EVIDENCE: IV, Retrospective study.

Signature of the vascular tumor microenvironment as a marker of the therapeutic response to doxorubicin in a preclinical model of osteosarcoma.

Predicting a response of osteosarcoma patients to chemotherapy, such as doxorubicin or high-dose methotrexate cocktail, remains a challenge in the clinic. Moreover, the prognostic value of currently used necrosis analysis is debatable. New markers of the therapeutic response or the prognostic response are urgently needed. The microenvironment plays a key role in the vascularization of highly heterogeneous tumors. Using the syngeneic MOS-J mouse model of osteosarcoma, we focused our study on the immunohistochemistry of tumor vascularization in order to identify new vessel markers, and to search for potential markers of the therapeutic response. Endomucin+, CD31+, and α-SMA+-positive elements were quantified in control (n=6) and doxorubicin-treated (n=6) mice in three different intra-tumor locations. We also used co-labeling to assess CD31+/Endomucin+ and CD31+/α-SMA+ co-expression. We identified a central tumor zone with a low vascularization profile for all of these markers. We identified two distinct types of vessels: CD31+/Endomucin+ vessels with a sprouting, neo-angiogenic, interlaced appearance, and CD31+/α-SMA+ vessel with a well-defined, mature structure. Doxorubicin appeared to reduce CD31+ expression in the tumor invasion front. In the doxorubicin-sensitive model, there were four times more CD31+/α-SMA+ elements than in the poorly responsive model. Therefore, we propose a methodology based on immunohistochemistry and multiplexed immunofluorescence to use endomucin as a promising new vascular marker in the osteosarcoma model. Moreover, our results suggest that CD31+/α-SMA+ vessels could be considered to be indicators of vasculature normalization and they may be used as specific markers of a good therapeutic response.