An update about molecular biology techniques to detect orthopaedic implant-related infections

Despite different criteria to diagnose a prosthetic joint infection (PJI), aetiological diagnosis of the causing microorganism remains essential to guide treatment. Molecular-biology-based PJI diagnosis is progressing (faster, higher specificity) in different techniques, from the experimental laboratory into clinical use. Multiplex polymerase chain reaction techniques (custom- made or commercial) provide satisfactory results in clinical series of cases, with specificity close to 100% and sensitivity over 70–80%. Next-generation metagenomics may increase sensitivity while maintaining high specificity. Molecular biology techniques may represent, in the next five years, a significant transformation of the currently available microbiological diagnosis in PJI

Regulatory authorities and orthopaedic clinical trials on expanded mesenchymal stem cells

This article is published with open access at Springerlink.comSkeletal injuries requiring bone augmentation techniques are increasing in the context of avoiding or treating difficult cases with bone defects, bone healing problems, and bone regeneration limitations. Musculoskeletal severe trauma, osteoporosis-related fractures, and conditions where bone defect, bone collapse or insufficient bone regeneration occur are prone to disability and serious complications. Bone cell therapy has emerged as a promising technique to augment and promote bone regeneration. Interest in the orthopaedic community is considerable, although many aspects related to the research of this technique in specific indications may be insufficiently recognised by many orthopaedic surgeons. Clinical trials are the ultimate research in real patients that may confirm or refute the value of this new therapy. However, before launching the required trials in bone cell therapy towards bone regeneration, preclinical data is needed with the cell product to be implanted in patients to ensure safety and efficacy. These preclinical studies support the end-points that need to be evaluated in clinical trials. Orthopaedic surgeons are the ultimate players that, through their research, would confirm in clinical trials the benefit of bone cell therapies. To further foster this research, the pathway to eventually obtain authorisation from the National Competent Authorities and Research Ethics Committees under the European regulation is reviewed, and the experience of the REBORNE European project offers information and important clues about the current Voluntary Harmonization Procedure and other opportunities that need to be considered by surgeons and researchers on the topicThis work was supported in part by the European Commission, Seventh Framework Programme (FP7), through the REBORNE Project, grant agreement no. 24187

Implantation of autologous expanded mesenchymal stromal cells in hip osteonecrosis through percutaneous forage: Evaluation of the operative technique

Bone forage to treat early osteonecrosis of the femoral head (ONFH) has evolved as the channel to percutaneously deliver cell therapy into the femoral head. However, its efficacy is variable and the drivers towards higher efficacy are currently unknown. The aim of this study was to evaluate the forage technique and correlate it with the efficacy to heal ONFH in a multicentric, multinational clinical trial to implant autologous mesenchymal stromal cells expanded from bone marrow (BM‐hMSCs). Methods: In the context of EudraCT 2012‐002010‐39, patients with small and medium‐sized (mean volume = 13.3%, range: 5.4 to 32.2) ONFH stage II (Ficat, ARCO, Steinberg) C1 and C2 (Japanese Investigation Committee (JIC)) were treated with percutaneous forage and implantation of 140 million BM‐hMSCs in a standardized manner. Postoperative hip radiographs (AP—anteroposterior and lateral), and MRI sections (coronal and transverse) were retrospectively evaluated in 22 patients to assess the femoral head drilling orientation in both planes, and its relation to the necrotic area. Results: Treatment efficacy was similar in C1 and C2 (coronal plane) and in anterior to posterior (transverse plane) osteonecrotic lesions. The drill crossed the sclerotic rim in all cases. The forage was placed slightly valgus, at 139.3 ± 8.4 grades (range, 125.5–159.3) with higher dispersion (f = 2.6; p = 0.034) than the anatomical cervicodiaphyseal angle. Bonferroni’s correlation between both angles was 0.50 (p = 0.028). More failures were seen with a varus drill positioning, aiming at the central area of the femoral head, outside the weight‐bearing area (WBA) (p = 0.049). In the transverse plane, the anterior positioning of the drill did not result in better outcomes (p = 0.477). Conclusion: The forage drilling to deliver cells should be positioned within the WBA in the coronal plane, avoiding varus positioning, and central to anterior in the transverse plane. The efficacy of delivered MSCs to regenerate bone in ONFH could be influenced by the drilling direction. Standardization of this surgical technique is desirable.The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/FP7-HEALTH-2009): REBORNE Project, Grant Agreement 24187

Defining the most effective patient blood management combined with tranexamic acid regime in primary uncemented total hip replacement surgery

The application of patient blood management (PBM) combined with tranexamic acid administration (TXA) results in decreased total blood loss volume (TVB) and transfusions in total hip replacements (THRs). Dosages, timing, and routes of administration of TXA are still under debate as all these aspects, as well as interpatient variations, may a ect the e cacy of the protocol. This study aims to examine the e ectiveness of timing and route of administration of TXA in combination with PBM by reducing the TBV following THR surgery. Consecutive primary uncemented THRs operated by a single surgical and anaesthetic team had the data prospectively collected and then retrospectively studied. Five treatment groups were formed, reflecting the progressive evolution of our protocol. Group 1 included patients managed with PBM alone (preoperative erythrocyte mass optimisation to at least 14 g/dL haemoglobin (Hb), hypotensive spinal anaesthesia and restrictive red blood cell transfusion criteria). Group 2 included patients with PBM and topical 3 g TXA diluted in normal saline to a total volume of 50 mL. Group 3 were patients with PBM and an IV dose of 20 mg/kg TXA at induction, followed by 20 mg/kg TXA as a continuous infusion for the duration of the operation. Group 4 consisted of patients managed as per Group 3 plus another 20 mg/kg TXA at three-hour post-procedure. Group 5 (combined): PBM and IV TXA as per Group 4 and topical TXA as per Group 2. A generalised linear model with the treatment group as an independent variable was modelled, using TBV as the dependent variable. The transfusion rate for all groups was 0%. TBV at 24 h, oscillated from 613.5 337.63 mL in Group 1 to 376.29 135.0 mL in Group 5. TBV at 48 h oscillated from 738.3 367.3 mL (PBM group) to 434 155.2 mL (PBM + combined group). The multivariate regression model confirmed a significant decrease of TBV in all groups with TXA compared with the PBM-only group. Overweight and preoperative Hb were confirmed to significantly influence TBV. The optimal regime to achieve the least TBV and a transfusion rate of 0% requires PBM and one loading 20 mg/kg dose of TXA, followed by continuous infusion of 20 mg/kg for the duration of the operation in uncemented THRs. Additional doses of TXA did not add a clear benefi

Explant analysis and implant registries are both needed to further improve patient safety

In the early days of total joint replacement, implant fracture, material problems and wear presented major problems for the long-term success of the operation. Today, failures directly related to the implant comprise only 2–3% of the reasons for revision surgeries, which is a result of the material and design improvements in combination with the standardization of pre-clinical testing methods and the post-market surveillance required by the legal regulation. Arthroplasty registers are very effective tools to document the long-term clinical performance of implants and implantation techniques such as fixation methods in combination with patient characteristics. Revisions due to implant failure are initially not reflected by the registries due to their small number. Explant analysis including patient, clinical and imaging documentation is crucial to identify failure mechanisms early enough to prevent massive failures detectable in the registries. In the past, early reaction was not always successful, since explant analysis studies have either been performed late or the results did not trigger preventive measures until clinical failures affected a substantial number of patients. The identification of implant-related problems is only possible if all failures are reported and related to the number of implantations. A system that analyses all explants from revisions attributed to implant failure is mandatory to reduce failures, allowing improvement of risk assessment in the regulatory proces

Limiting spread of COVID-19 in an orthopaedic department-a perspective from Spain

Besides national and international recommendations, orthopaedic departments face significant changes in daily activity and serious issues to maintain their standards in musculoskeletal care during the pandemic Covid-19 crisis that we are facing. This report retrospectively addresses measures that were progressively put in place to modify in a week time the activity of a busy orthopaedic department in a large tertiary university hospital in face of the pandemic. Surgical priorities and surgical outcomes are key aspects to consider. The experience may offer some insight to areas where the spread of the disease may be slower or delayed. Abrupt stop of scheduled surgery and clinics is useful to adapt an orthopaedic department to the overall hospital resource reorganization. Orthopaedic surgeons need to be aware of the risks to patients and personnel in view of underdiagnosed cases, which make pre-operative Covid-19 evaluation mandatory for all surgical case