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.

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.

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.

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.

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.

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.

Pilot Study of an e-Cohort to Monitor Adverse Event for Patient with Hip Prostheses from Clinical Data Warehouse.

Hip arthroplasty represents a large proportion of orthopaedic activity, constantly increasing. Automating monitoring from clinical data warehouses is an opportunity to dynamically monitor devices and patient outcomes allowing improve clinical practices. Our objective was to assess quantitative and qualitative concordance between claim data and device supply data in order to create an e-cohort of patients undergoing a hip replacement. We performed a single-centre cohort pilot study, from one clinical data warehouse of a French University Hospital, from January 1, 2010 to December 31, 2019. We included all adult patients undergoing a hip arthroplasty, and with at least one hip medical device provided. Patients younger than 18 years or opposed to the reuse of their data were excluded from the analysis. Our primary outcome was the percentage of hospital stays with both hip arthroplasty and hip device provided. The patient and stay characteristics assessed in this study were: age, sex, length of stay, surgery procedure (replacement, repositioning, change, or reconstruction), medical motif for surgery (osteoarthritis, fracture, cancer, infection, or other) and device provided (head, stem, shell, or other). We found 3,380 stays and 2,934 patients, 96.4% of them had both a hip surgery procedure and a hip device provided. These data from different sources are close enough to be integrated in a common clinical data warehouse.

Evaluation of the Chemotherapy Drug Response Using Organotypic Cultures of Osteosarcoma Tumours from Mice Models and Canine Patients.

Improvements in the clinical outcome of osteosarcoma have plateaued in recent decades with poor translation between preclinical testing and clinical efficacy. Organotypic cultures retain key features of patient tumours, such as a myriad of cell types organized within an extracellular matrix, thereby presenting a more realistic and personalised screening of chemotherapeutic agents ex vivo. To test this concept for the first time in osteosarcoma, murine and canine osteosarcoma organotypic models were maintained for up to 21 days and in-depth analysis identified proportions of immune and stromal cells present at levels comparable to that reported in vivo in the literature. Cytotoxicity testing of a range of chemotherapeutic drugs (mafosfamide, cisplatin, methotrexate, etoposide, and doxorubicin) on murine organotypic culture ex vivo found limited response to treatment, with immune and stromal cells demonstrating enhanced survival over the global tumour cell population. Furthermore, significantly decreased sensitivity to a range of chemotherapeutics in 3D organotypic culture relative to 2D monolayer was observed, with subsequent investigation confirming reduced sensitivity in 3D than in 2D, even at equivalent levels of drug uptake. Finally, as proof of concept for the application of this model to personalised drug screening, chemotherapy testing with doxorubicin was performed on biopsies obtained from canine osteosarcoma patients. Together, this study highlights the importance of recapitulating the 3D tumour multicellular microenvironment to better predict drug response and provides evidence for the utility and possibilities of organotypic culture for enhanced preclinical selection and evaluation of chemotherapeutics targeting osteosarcoma.

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.

Role of real-world digital data for orthopedic implant automated surveillance: a systematic review.

INTRODUCTION: Data collection automation through the reuse of real-world digital data from clinical data warehouses (CDW) could represent a great opportunity to improve medical device monitoring. For instance, this approach is starting to be used for the design of automated decision support systems for joint replacement monitoring. However, a number of obstacles remains, such as data quality and interoperability through the use of common and regularly updated terminologies, and the use of a Unique Device Identifier (UDI). AREAS COVERED: To present the existing models of automated surveillance of orthopedic devices, a systematic review of initiatives using real-world digital health data to monitor joint replacement surgery was performed following the PRISMA 2020 guidelines. The main objective was to identify the data sources, the target populations, the population size, the device location, and the main results of studies on such initiatives. EXPERT OPINION: Analysis of the identified studies showed that real-world digital data offer many opportunities for improving the automation of monitoring in orthopedics. The contribution of real-world data, especially through natural language processing, UDI use in CDW and the integration of device databases, is needed for automated and more robust health surveillance.

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.).

Comparison of Knowledge Databases to Be Used in Automated Monitoring of Orthopedic Medical Devices.

Surveillance and traceability of medical devices (MD) is a challenge in health care systems. In the perspective of reusing EHR data to automate the monitoring of medical devices, we carried out a comparison of the main MD knowledge bases (MD-KDB) currently available in France. Four MD-KDBs (ANSM, Gudid, Exhausmed and CIOdm) were compared quantitatively and through an example of a shoulder prosthesis. The number of MDs registered differs from one MD-KDB to another. Domain terminologies used in MD-KDBs differ in terms of granularity and in the ease of querying. Waiting EUDAMED, the European MD-KDB, it seems necessary so far to use and combine information coming from several MD-KDBs to address MD monitoring.

Osteonecrosis of the Femoral Head Safely Healed with Autologous, Expanded, Bone Marrow-Derived Mesenchymal Stromal Cells in a Multicentric Trial with Minimum 5 Years Follow-Up.

Background: Osteonecrosis (ON) of the femoral head represents a potentially severe disease of the hip where the lack of bone regeneration may lead to femoral head collapse and secondary osteoarthritis, with serious pain and disability. The aim of this European, multicentric clinical trial was to prove safety and early efficacy to heal early femoral head ON in patients through minimally invasive surgical implantation of autologous mesenchymal stromal cells (MSC) expanded from bone marrow (BM) under good manufacturing practices (GMP). Methods: Twenty-two patients with femoral head ON (up to ARCO 2C) were recruited and surgically treated in France, Germany, Italy and Spain with BM-derived, expanded autologous MSC (total dose 140 million MSC in 7 mL). The investigational advanced therapy medicinal product (ATMP) was expanded from BM under the same protocol in all four countries and approved by each National Competent Authority. Patients were followed during two years for safety, based on adverse events, and for efficacy, based on clinical assessment (pain and hip score) and imaging (X-rays and MRIs). Patients were also reviewed after 5 to 6 years at latest follow-up for final outcome. Results: No severe adverse event was recalled as related to the ATMP. At 12 months, 16/20 per protocol and 16/22 under intention-to-treat (2 drop-out at 3 and 5 months) maintained head sphericity and showed bone regeneration. Of the 4 hips with ON progression, 3 required total hip replacement (THR). At 5 years, one patient (healed at 2 years visit) was not located, and 16/21 showed no progression or THR, 4/21 had received THR (all in the first year) and 1 had progressed one stage without THR. Conclusions: Expanded MSCs implantation was safe. Early efficacy was confirmed in 80% of cases under protocol at 2 years. At 5 years, the overall results were maintained and 19% converted to THR, all in the first year.

Soft tissue reconstruction after pelvic amputation: The efficacy and reliability of free fillet flap reconstruction.

BACKGROUND: The majority of hindquarter amputation defects can be reconstructed with local anterior or posterior thigh flaps. Less than 5% of soft tissue defects require free flap reconstruction after tumour resection. Lower extremity fillet flap is described for reconstructing such defects, but the majority of publications are case reports or short single institutional series. There is a lack of data regarding the oncological outcomes of this highly selected patient group. METHODS: Three tertiary sarcoma units treated twelve patients with hindquarter amputation or hip disarticulation for oncological indications with a free flap reconstruction of the soft tissue defect. RESULTS: The median age of patients was 60 (range 12-76) years. Bone resection was carried out through the SI-joint in six patients and through the sacrum in five patients, with one patient undergoing hip disarticulation. Nine patients had R0 resection margin and three had R1 resection. The median surgical time and flap ischaemia time was 420 (249-650) and 89 (64-210) min, respectively. Median hospital and ICU stay was 18 (10-42) and 3 (1-8) days, respectively. Median blood loss was 2400 (950-10000) ml. There were three returns to theatre due to vascular compromise, with one total flap loss due to arterial thrombosis. Overall survival was 58% (95%CI 28-91%) both at 1-year and at 3-years. DISCUSSION: Carefully selected patients requiring hindquarter amputation with extensive soft tissue defect necessitating free flap reconstruction can be reconstructed with a lower extremity free fillet flap with low rate of local wound complications. Survival of these patients is similar to that in patients requiring less extensive resection.

Frontiers in non-union research.

Multifactorial aetiology defines non-unions, with a biological and a mechanical distortion of the timeline of bone healing.Research on new advances to increase osteogenesis and promote non-union healing is strongly directed towards new forms of cell products.Basic science and research on non-union treatments is needed to compile preclinical data on new treatments.Bone marrow concentration and expanded mesenchymal stromal cells still require extensive clinical research to confirm efficacy in non-union treatment.Solid preclinical studies, precise cell product definition and preparation, and appropriate ethical and regulatory approvals are needed to assess new advanced therapy medicinal products. Cite this article: EFORT Open Rev 2020;5:574-583. DOI: 10.1302/2058-5241.5.190062.

In situ production of pre-vascularized synthetic bone grafts for regenerating critical-sized defects in rabbits.

Reconstructing large bone defects caused by severe trauma or resection of tumors remains a challenge for surgeons. A fibula free flap and its vascularized bed can be transplanted to the reconstruction site to achieve healing. However, this technique adds morbidity, and requires microsurgery and sculpting of the bone tissue to adapt the graft to both the vasculature and the anatomy of the defect. The aim of the current study was to evaluate an alternative approach consisting of the in situ production of a pre-vascularized synthetic bone graft and its subsequent transplantation to a critical-sized bone defect. 3D printed chambers containing biphasic calcium phosphate (BCP) granules, perfused by a local vascular pedicle, with or without the addition of stromal vascular fraction (SVF), were subcutaneously implanted into New Zealand White female rabbits. SVF was prepared extemporaneously from autologous adipose tissue, the vascular pedicle was isolated from the inguinal site, while BCP granules alone served as a control group. After 8 weeks, the constructs containing a vascular pedicle exhibited abundant neovascularization with blood vessels sprouting from the pedicle, leading to significantly increased vascularization compared to BCP controls. Pre-vascularized synthetic bone grafts were then transplanted into 15 mm critical-sized segmental ulnar defects for a further 8 weeks. Micro-CT and decalcified histology revealed that pre-vascularization of synthetic bone grafts led to enhanced bone regeneration. This pre-clinical study demonstrates the feasibility and efficacy of the in situ production of pre-vascularized synthetic bone grafts for regenerating large bone defects, thereby addressing an important clinical need. STATEMENT OF SIGNIFICANCE: The current gold standard in large bone defect regeneration is vascularized fibula grafting. An alternative approach consisting of in situ production of a pre-vascularized synthetic bone graft and its subsequent transplantation to a bone defect is presented here. 3D printed chambers were filled with biphasic calcium phosphate granules, supplemented with autologous stromal vascular fraction and an axial vascular pedicle and subcutaneously implanted in inguinal sites. These pre-vascularized synthetic grafts were then transplanted into critical-sized segmental ulnar defects. Micro-CT and decalcified histology revealed that the pre-vascularized synthetic bone grafts led to higher bone regeneration than non-vascularized constructs. An alternative to vascularized fibula grafting is provided and may address an important clinical need for large bone defect reconstruction.

Regeneration of segmental defects in metatarsus of sheep with vascularized and customized 3D-printed calcium phosphate scaffolds.

Although autografts are considered to be the gold standard treatment for reconstruction of large bone defects resulting from trauma or diseases, donor site morbidity and limited availability restrict their use. Successful bone repair also depends on sufficient vascularization and to address this challenge, novel strategies focus on the development of vascularized biomaterial scaffolds. This pilot study aimed to investigate the feasibility of regenerating large bone defects in sheep using 3D-printed customized calcium phosphate scaffolds with or without surgical vascularization. Pre-operative computed tomography scans were performed to visualize the metatarsus and vasculature and to fabricate customized scaffolds and surgical guides by 3D printing. Critical-sized segmental defects created in the mid-diaphyseal region of the metatarsus were either left empty or treated with the 3D scaffold alone or in combination with an axial vascular pedicle. Bone regeneration was evaluated 1, 2 and 3 months post-implantation. After 3 months, the untreated defect remained non-bridged while the 3D scaffold guided bone regeneration. The presence of the vascular pedicle further enhanced bone formation. Histology confirmed bone growth inside the porous 3D scaffolds with or without vascular pedicle inclusion. Taken together, this pilot study demonstrated the feasibility of precised pre-surgical planning and reconstruction of large bone defects with 3D-printed personalized scaffolds.

Survival and complications in hinged knee reconstruction prostheses after distal femoral or proximal tibial tumor resection: A retrospective study of 161 cases.

INTRODUCTION: Hinged knee megaprostheses are mainly used for reconstruction after tumor resection. They may incur complications, but this has not been assessed in the French literature, except in small series at short follow-up. We therefore conducted a large-scale nationwide multicenter retrospective study with a minimum 5 years' follow-up. The objectives were (1) to compare survival between distal femoral and proximal tibial reconstruction prostheses, and (2) to analyze complications and failure. HYPOTHESIS: Distal femoral hinged reconstruction prostheses show longer survival with fewer complications than proximal tibial prostheses. MATERIAL AND METHODS: One hundred sixty-one patients were included: 118 in the distal femoral group, and 43 in the proximal tibial group. Tumors were mostly osteosarcomas (90 cases) or chondrosarcomas (31 cases). Mean age was 37 years (range, 12-86 years). Complications were assessed on the Henderson classification. Failure was defined by prosthesis anchor exchange or amputation. RESULTS: At a mean 9 years' follow-up (range, 5-23 years), implant survival was longer in the distal femoral group: 5- and 10-year survival, 84% [95% CI, 75-89] and 70% [95% CI, 59-79] versus 74% [95% CI, 69-85] and 43% [95% CI, 23-61] (p=0.02). Revision surgery for complications mainly concerned aseptic loosening (19%, 30 cases) or deep infection (16%, 25 cases) and more often involved the proximal tibia (65% vs. 43%, 28 vs. 51 cases; OR 2.4 [95% CI, 1.2-5.1]; p=0.02). DISCUSSION: Hinged knee reconstruction prosthesis is a solution in tumoral pathology, but with a high risk of complications (loosening and infection) and a higher failure rate in the proximal tibial reconstruction prosthesis. LEVEL OF EVIDENCE: IV, case series.

Fixed-hinge cemented modular implants: An effective reconstruction technique following primary distal femoral bone tumor resection. A 136-case multicenter series.

BACKGROUND: Reconstruction by endoprosthesis is widespread after bone tumor resection. The design and type of fixation and of hinge remain a matter of debate. The aim of the present study was to assess survival, complications and functional results in a homogeneous series of adult patients undergoing bone defect reconstruction following distal femoral tumor resection, using a single model of fixed-hinge cemented endoprosthesis, at a minimum 5 years' follow-up. HYPOTHESIS: The study hypotheses were that loosening and infection are the main causes of failure, and that this type of reconstruction is reliable following distal femoral resection. PATIENTS AND METHODS: All patients aged over 17 years undergoing reconstruction using the Stanmore Mets® fixed-hinge cemented modular endoprosthesis following distal femoral resection for primary bone tumor in 4 French reference centers between 2004 and 2013 were included. Epidemiological data, MSTS functional score, clinical and radiological examination results, complications and survival with types of failure according to the Henderson classification were assessed. RESULTS: One hundred and thirty-six patients (68 male, 68 female; mean age, 41.2 years [range, 17-77 years]) were included. Mean follow-up was 81 months [range, 61-134 months]. Thirty-two patients (38%) experienced a total 67 complications requiring surgical revision: mainly infection (n=28) or mechanical failure (n=26). Overall implant survival was 78% at 5 years. There were 30 implant failures on the Henderson classification. Mean MSTS score was 82%. DISCUSSION: The present results are comparable to those of the literature and for other types of reconstruction. Recent meta-analyses suggest that type of hinge and of stem fixation have little effect on implant survival. International comparative studies are needed to determine the exact role of each type of reconstruction according to the patient profile. LEVEL OF EVIDENCE: IV, multicenter retrospective series.