Vascular study of decellularized porcine long bones: Characterization of a tissue engineering model.

INTRODUCTION: Massive bone allografts enable the reconstruction of critical bone defects in numerous conditions (e.g. tumoral, infection or trauma). Unfortunately, their biological integration remains insufficient and the reconstruction may suffer from several postoperative complications. Perfusion-decellularization emerges as a tissue engineering potential solution to enhance osseointegration. Therefore, an intrinsic vascular study of this novel tissue engineering tool becomes essential to understand its efficacy and applicability. MATERIAL AND METHODS: 32 porcine long bones (humeri and femurs) were used to assess the quality of their vascular network prior and after undergoing a perfusion-decellularization protocol. 12 paired bones were used to assess the vascular matrix prior (N = 6) and after our protocol (N = 6) by immunohistochemistry. Collagen IV, Von Willebrand factor and CD31 were targeted then quantified. The medullary macroscopic vascular network was evaluated with 12 bones: 6 were decellularized and the other 6 were, as control, not treated. All 12 underwent a contrast-agent injection through the nutrient artery prior an angio CT-scan acquisition. The images were processed and the length of medullary vessels filled with contrast agent were measured on angiographic cT images obtained in control and decellularized bones by 4 independent observers to evaluate the vascular network preservation. The microscopic cortical vascular network was evaluated on 8 bones: 4 control and 4 decellularized. After injection of gelatinous fluorochrome mixture (calcein green), non-decalcified fluoroscopic microscopy was performed in order to assess the perfusion quality of cortical vascular lacunae. RESULTS: The continuity of the microscopic vascular network was assessed with Collagen IV immunohistochemistry (p-value = 0.805) while the decellularization quality was observed through CD31 and Von Willebrand factor immunohistochemistry (p-values <0.001). The macroscopic vascular network was severely impaired after perfusion-decellularization; nutrient arteries were still patent but the amount of medullary vascular channels measured was significantly higher in the control group compared to the decellularized group (p-value <0.001). On average, the observers show good agreement on these results, except in the decellularized group where more inter-observer discrepancies were observed. The microscopic vascular network was observed with green fluoroscopic signal in almost every canals and lacunae of the bone cortices, in three different bone locations (proximal metaphysis, diaphysis and distal metaphysis). CONCLUSION: Despite the aggressiveness of the decellularization protocol on medullary vessels, total porcine long bones decellularized by perfusion retain an acellular cortical microvascular network. By injection through the intact nutrient arteries, this latter vascular network can still be used as a total bone infusion access for bone tissue engineering in order to enhance massive bone allografts prior implantation.

Are C-reactive protein (CRP) and neutrophil to lymphocyte ratio (NLR) predictive markers of successful two-stage prosthetic joint infection management?

The treatment of prosthetic joint infections (PJI) regularly involves a two-stage surgical strategy. The second stage is generally performed when the surgeon estimates that the infection is under control based on either the treatment length or clinical and biological data. We have raised the question whether standardization of C-reactive protein (CRP) and neutrophil to lymphocyte ratio (NLR) values could be either indicative of infection control or predictive of infection recurrence. This was an analytical retrospective and monocentric cross-sectional observational study. The CRP and NLR values were recorded prior to the second-stage surgery in a sample of 100 patients who underwent a two-stage revision arthroplasty following a PJI, and these values were correlated with the absence of infectious recurrence within a 2-year follow-up. The statistical analysis consisted of evaluating the diagnostic validity of each marker, first individually, and then in combination. CRP was shown associated with a 68% sensitivity, 40% specificity, 27% positive predictive value (PPV), and 79% negative predictive value (NPV). The ROC curve was 51.1%. The NLR displayed a 12% sensitivity, 89% specificity, 27% PPV, and 75% NPV. The ROC curve was 47.9%. The combination of the two markers did not fundamentally improve the statistical results, with only a 43% concordance of the two markers, 27% sensitivity, 84% specificity, 37% PPV, and 77% NPV. Measuring CRP and NLR values, either individually or in combination, before the second-stage revision arthroplasty did not turn out to be predictive of either infection recurrence or cure within two years of follow-up. Therefore, an absolute test is still lacking, which would enable us to predict without failure the absence of control or the control of a PJI before or after second-stage revision. Level of evidence: Level III, retrospective cross-sectional study.

Unilateral versus simultaneous bilateral total hip arthroplasty. The Belgian experience.

Bilateral hip osteoarthritis is frequent. The safety and patient selection for simultaneous bilateral total hip arthroplasty (SBTHA) are still debated. The purpose of this article is to share our experience and assess if performing SBTHA carries more risk than unilateral total hip arthroplasty (UTHA). METHODS: A retrospective data analysis was performed on 468 patients who underwent either UTHA (418 patients) or SBTHA (50 patients) using a direct anterior approach between June 2016 and December 2020. Apart from SBTHA patients being significantly younger, there was no significant preoperative difference in demographics, comorbidities, surgical variables and biological values between the two groups. Primary outcomes were 90-days emergency room (ER) visit and readmission, as well as 90-days minor and major complications. Secondary outcomes were length of stay (LOS), operative time and blood loss. RESULTS: 90-days ER visit (p=0.244), 90- days readmission (p=0.091), overall complications rate (p=0.376), minor complications (p=0.952) and major complications (p=0.258) were not statistically different between the two groups. Operative time and average LOS were significantly longer in the SBTHA group (p<0.001). Blood loss was significantly higher (p<0.001) in the SBTHA group. However, no difference in the transfusion rate between the two groups was observed (p=0.724). CONCLUSION: Complication rate, 90- days hospital readmission and 90-days ER visit were similar between the two groups. This study shows that performing SBTHA is a safe, effective, and doesn't carry additional risks for patients with bilateral symptomatic osteoarthritis.

Female representation in orthopedic surgery: where do we stand in Belgium ?

Female underrepresentation in Orthopedic Surgery and Traumatology is a well-known issue worldwide, including in Belgium. Most of the literature comes from northern America. This two-part study aims to quantify the female workforce in orthopedic surgery in Belgium and assess the presence of unconscious biases among active orthopedic surgeons. Epidemiological data from national registries, orthopedic societies and universities in Belgium were analyzed. This included data on medical students, residents, active orthopedic surgeons and awards given by a Belgian orthopedic society. Additionally, a questionnaire was administered to Belgian orthopedic surgeons, assessing their perceptions of gender stereotypes and potential unconscious biases. 90 participants responded with 70% of men and mean age was 36 years old. The data revealed that 12% of active orthopedic surgeons in Belgium were women in 2020. However, the representation f women was higher among residents, with a thirty percent distribution. In one university, women had a slightly higher chance of getting accepted in the orthopedic training then men. The questionnaire results indicated the presence of unconscious bias regarding subspecialties, which aligned with the actual distribution. Women tend to specialize more in upper limb surgery and pediatrics while men focus more frequently on lower limb surgery. The findings highlight the need for addressing the underrepresentation of women in orthopedic surgery and traumatology in Belgium. If the current rate of progress continues, it is projected that 30% of active orthopedic surgeons will be female by the year 2074. Identifying and addressing factors contributing to the underrepresentation, such as lack of mentorship, unconscious biases, visibility issues, and discrimination, is crucial for empowering future female orthopedic surgeons and fostering diversity in the field. Collaboration among European universities and orthopedic societies can play a vital role in reducing barriers and promoting gender equality in orthopedic surgery and traumatology.

PMMA-cement anterior column reconstruction in surgical treatment of spondylodiscitis.

Introduction and research question: This paper explains how antibiotic loaded cement can be used in surgical treatment of spondylodiscitis to reconstruct the anterior column of the spine. Material and methods: 35 consecutive surgical procedures performed for spondylodiscitis were collected over a 11-year period and charts were reviewed. Most infections were caused mainly by staphylococcus spp (n = 16), streptococcus spp (n = 8) and pseudomonas spp (n = 4). Most patients had long standing but unsuccessful antibiotic therapy (median 42 days). Other indications included instability, neurologic deficit, abscess, and patients were generally in very poor medical condition. Results: Anterior debridement was followed by a partial cavity filling with surgical high viscosity PMMA cement in all cases. Cement was a high viscosity gentamycin loaded cement, that was placed in the cavity created by debridement under the direct eye control. In 25 cases, a part of the cavity was filled with freeze dried cancellous bone allograft rehydrated in rifampicin. Spine was further stabilized with an anterior plate in 15 cases, with short (+1/+1) posterior instrumentation in 5 cases, and a long (≥ +2/+2) posterior instrumentation in 11 cases. In four patients, spine was left un-instrumented. Immediate, unrestricted mobilization was always authorized after surgery. None of the patients were reoperated neither for mechanical failure nor for infection relapse. Conclusion: This report supports the idea that surgical bone cement is an efficient gap filler when used through anterior approach. For small as well as for large defects, it can help to reconstruct the anterior column and locally control the infection in combination with additional stabilization and optimal intravenous and oral antibiotic treatment.

Neutrophil-to-lymphocyte ratio (NLR) distribution shows an advantage compared to C-reactive protein (CRP) for the early inflammation monitoring after total hip arthroplasty.

C-reactive protein (CRP) distribution has been used to monitor early inflammation after total hip arthroplasty (THA). Neutrophil to lymphocyte ratio (NLR) is a new and cheap inflammatory marker. This study aimed to verify whether Neutrophil to lymphocyte ratio (NLR) distribution has an advantage when compared to C-reactive protein (CRP) distribution for the inflammation monitoring after total hip arthroplasty (THA). 116 THA patients were retrospectively selected over a 2 years period. They all had available blood tests preoperatively and at postoperative days 2, 4 and 42. Median peak values were compared between CRP and NLR. The effect of demographics on CRP and NLR was tested. At days 4 and 42, 100% and 16.3% of patients had not reached normal CRP (< 10mg/L) while 56.8% and 6.8% of patients had not reached normal NLR (<5) respectively. There was no effect of demographics on NLR except for age. Older patients had higher NLR (p 0.037). NLR showed a quicker return to normal than CRP. Our results show that NLR seems to be a better marker to follow inflammation after THA than CRP.

Diagnosis of prosthetic joint infection with alpha-defensin using a lateral flow device: a multicentre study.

AIMS: The purpose of this current multicentre study is to analyse the presence of alpha-defensin proteins in synovial fluid using the Synovasure lateral flow device and to determine its diagnostic reliability and accuracy compared with the prosthetic joint infection (PJI) criteria produced by the Musculoskeletal Infection Society (MSIS). PATIENTS AND METHODS: A cohort of 121 patients comprising 85 total knee arthroplasties and 36 total hip arthroplasties was prospectively evaluated between May 2015 and June 2016 in three different orthopaedic centres. The tests were performed on patients with a chronically painful prosthesis undergoing a joint aspiration in a diagnostic pathway or during revision surgery. RESULTS: Based on the MSIS criteria, 34 patients (28%) would have had a PJI, and 87 patients had no PJI. Testing with the lateral flow device had a sensitivity of 97.1% (95% confidence intervals (CI) 84.5 to 99.9) and a specificity of 96.6% (95% CI 90.3 to 99.2). The positive predictive value was 91.7% (95% CI 77.7% to 98.3), and the negative predictive value was 98.8% (95% CI 93.6 to 99.9). Receiver operator characteristics analysis demonstrated an area under the curve for the Synovasure test of 0.97 (95% CI 0.93 to 1.00). CONCLUSION: Our findings suggest that the Synovasure test has an excellent diagnostic performance to confirm or reject the diagnosis of a PJI. The results are promising for the care of the painful or problematic knee and hip joint arthroplasty and the test should be considered as part of the diagnostic toolbox for PJIs. Cite this article: Bone Joint J 2017;99-B:1176-82.

Bone morphotypes of the varus and valgus knee.

BACKGROUND: Coronal deformity correction with total knee arthroplasty (TKA) is an important feature in the treatment of osteoarthritis (OA). The hypothesis of this study was that bone morphology would be different in varus and valgus deformity, both before osteoarthritis development as well as during and after the disease process of OA. MATERIALS AND METHODS: Retrospective study with measurements on preoperative and postoperative full leg standing radiographs of 96 patients who underwent TKA. The included patients were selected for this study because they had an OA knee on one side and a non-arthritic knee on the contralateral side presenting the same type of alignment as the to-be-operated knee (varus or valgus alignment on both sides). The control group of 46 subjects was a group of patients with neutral mechanical alignment who presented for ligamentous problems. A single observer measured mechanical alignment, anatomical alignment, anatomical-mechanical femoral angle and intra-articular bone morphology parameters with an accuracy of 1°. RESULTS: Varus OA group has less distal femoral valgus (mLDFA 89°) than control group (87°) and valgus OA group (mLDFA 85°). Varus OA group has same varus obliquity as control group (MPTA 87°) but more than valgus OA group (MPTA 90°). Joint Line Congruency Angle (JLCA) is 3°open on lateral side in varus and medially open in valgus OA group (2°). The non-arthritic valgus group presents a constitutional mechanical valgus of 184° Hip-Knee-Ankle (HKA) angle. DISCUSSION: Varus deformity in OA as measured with an HKA angle (HKA) <177° is a combination of distal femoral wear, tibial varus obliquity and lateral joint line opening. Valgus deformity in OA with an HKA > 183° is a combination of femoral distal joint line obliquity and wear combined with medial opening due to medial collateral ligament stretching. The clinical importance of bone morphotype analysis is that it shows the intra-articular potential of alignment correction when mechanical axis cuts are performed. CONCLUSION: Bone morphology in varus and valgus deformity is different before and after osteoarthritis. Perpendicular cuts to mechanical axes do not necessarily lead to neutral mechanical axis. Constitutional mechanical valgus was observed as 184° HKA angle before the development of OA. LEVEL OF EVIDENCE: Level IV study.

Difficult to treat osteoarticulars infections : Focus on Mycobacterial and Fungal infection.

Bone and joint infections are rare but often devastating. While bacteria are most commonly encountered organisms, mycobacteria and fungi are less frequent. Management of the latter is often more complex, especially in the presence of foreign material. We will increasingly be faced with mycobacterial and fungal bone infections, as medical conditions and newer therapeutics lead to more immunosuppression. In this article, we will review osteomyelitis, septic arthritis and peri-prosthetic joint infections related to mycobacteria and fungi.

Joint awareness in osteoarthritis of the hip and knee evaluated with the 'Forgotten Joint' Score before and after joint replacement.

PURPOSE: To utilize the 'Forgotten Joint' Score (FJS), a 12-item questionnaire analysing the ability to forget the joint, for comparing preoperative status in osteoarthritic patients scheduled for total hip arthroplasty (THA) or total knee arthroplasty (TKA). Higher scores represent a better result with a maximum of 100. The hypothesis of this study was that a preoperative difference in favour of hip arthritis could eventually explain why THA is cited more often as a forgotten joint than TKA. METHODS: A prospective cohort study was conducted in 150 patients with either tricompartmental knee (n = 75) or hip osteoarthritis (n = 75). Patients completed FJS-12 scores preoperatively and 1 year postoperatively. RESULTS: A similar preoperative FJS-12 was observed for hip (22 (15)) and knee osteoarthritis (24 (17)) (n.s.). The postoperative FJS-12 score was significantly higher for THA (80 (24)) than for TKA (70 (27)) (p < 0.05). High reliability after 6 weeks was observed for the preoperative FJS-12 test-retest reliability (ICC = 0.87) in TKA. A preoperative floor effect of 15 % in THA and 0 % in TKA was found as well as a postoperative ceiling effect of 33 % in THA and 9 % in TKA. CONCLUSIONS: The clinical relevance of utilizing the FJS-12 as an instrument to evaluate outcome is strongly proposed for knee arthroplasty. In general, one is not aware of a healthy joint during the ADL, and it can therefore be regarded as 'forgotten'. The preoperative FJS-12 Score is a powerful tool to provide patients with clearer insights into their positive evolution after surgery. The use of the FJS-12 in THA is a topic for further research, as this study found that floor and ceiling effects limit its usefulness in studies evaluating clinical outcome in this area. LEVEL OF EVIDENCE: II.

Current opinions about coronal plane alignment in total knee arthroplasty: A survey article.

PURPOSE: To survey an audience of international knee surgeons about their current opinions on the analysis of coronal knee alignment and their objectives for postoperative alignment in total knee arthroplasty. METHODS: Survey of 300 surgeons from 32 different countries with an audience response system allowing three possible answers being either a positive or negative answer or an abstention. RESULTS: Surveyed surgeons perform rarely preoperative and postoperative full leg radiographs and evaluate radiological outcomes more with short films. The main trend in this survey was towards neutral mechanical alignment, however varus alignment is acceptable in constitutional varus patients. This residual varus should be obtained through a femoral varus cut rather than a tibial varus cut. The valgus knee can remain in slight valgus but most of the correction will be performed at the femoral level. The main objective of postoperative alignment in TKA is a joint line parallel to the floor and a central load-bearing axis through the middle of the arthroplasty. Surgeons prefer unicompartmental arthroplasty more for themselves than for their patients in case of medial bone on bone arthritis. CONCLUSIONS: Neutral mechanical axis with a joint line parallel to the floor and a centrally running load bearing axis remains the central scope of the surveyed surgeons. Because of the literature on residual varus it becomes more acceptable for the orthopaedic community to accept this type of outlier before aiming at a surgical correction.

Nocardia prosthetic knee infection successfully treated by one-stage exchange: case report and review.

A 64-year-old man with a history of sarcoidosis on corticosteroids and azathioprine was admitted to our hospital with complaints of worsening left knee pain and swelling for the past 3 weeks. His past medical history is also significant for severe osteoarthritis requiring a cemented total left knee arthroplasty 1 year ago. Diagnostic investigation during his hospital admission eventually led to the diagnosis of Nocardia nova knee prosthetic joint infection in the setting of a disseminated nocardiosis. He was successful treated by one-stage complete hardware exchange in conjunction with an adapted antibiotic therapy regimen (meropenem and doxycycline followed by ceftriaxone and doxycycline). Two years later, his recovery was deemed excellent.

Total knee arthroplasty in patients with substantial deformities using primary knee components.

PURPOSE: Although advocated for severe varus and valgus deformities, constrained implant designs are associated with a number of disadvantages in total knee arthroplasty (TKA). Combining a minimally invasive surgical approach with an interchangeable posterior stabilized (PS) implant design may allow adequate soft tissue balancing with a minimal amount of constraint and without residual instability. METHODS: Retrospectively 51 patients operated with the minimally invasive far medial subvastus approach for severe varus or valgus deformity, who underwent primary TKA with a fully interchangeable PS implant (Vanguard, Biomet Inc., Warsaw IN, USA) between 2009 and 2013 were examined. Soft tissue releases was performed using a piecrust needling technique. Preoperative alignment and surgical parameters were collected for all patients. All patients underwent preoperative and follow-up radiographic assessment and completed a battery of clinical assessments. RESULTS: All procedures were performed successfully, with alignment improving from a preoperative mean (SD) varus deformity of 165° (3°) and a mean (SD) valgus deformity of 196° (4.5°) to an overall mean (SD) postoperative mechanical alignment of 179.5° (3.0°). Nine patients had postoperative varus, while three patients had a postoperative valgus deviation from neutral alignment >3°. The mean change in joint line position in extension was -0.0 ± 0.6 mm. Clinical scores at final follow-up were excellent for both groups. CONCLUSIONS: Good TKA outcomes can be achieved in patients with substantial varus or valgus deformities using a combination of a minimally invasive far medial subvastus approach, interchangeable PS implants and soft tissue releases with a piecrust needling technique. LEVEL OF EVIDENCE: III.

Pneumococcal septic arthritis in adults: clinical analysis and review.

BACKGROUND: Septic arthritis (SA) is a rheumatological emergency that can lead to rapid joint destruction and irreversible loss of function. The most common pathogen causing SA is Staphylococcus aureus which is responsible for 37-65% of cases. Streptococcus pneumoniae is traditionally described as an uncommon cause of SA of a native joint. The objective of our study was to analyse clinical characteristics, treatment, and outcome of all cases of pneumococcal septic arthritis treated in our institution, and to compare them with other series published in the literature. MATERIALS AND METHODS: We conducted a retrospective study of pneumococcal SA identified among all cases of SA diagnosed in a teaching hospital of one thousand beds between 2004 and 2009. Diagnosis was based on culture of joint liquid or by the presence of pneumococcal bacteraemia and purulent (more than 50 000/mm(3) white blood cells with more than 90% neutrophils) joint fluid aspiration. RESULTS: Among 266 cases of SA, nine patients (3·3%) were diagnosed as having pneumococcal SA. The median age was 75 years. The main affected joint was the knee (7/9). No patient had more than one joint involved. Four patients suffered from concomitant pneumonia. Joint culture and blood cultures were positive in 7/9 and 5/9, respectively. Median (range) length of stay was 18 days (3-47 days). One patient with associated pneumococcal bacteraemia died 19 days after admission. Seven patients recovered completely. CONCLUSIONS: Streptococcus pneumoniae is now being increasingly recognized as a common agent of SA. This organism is frequently associated with pneumococcal pneumonia or bacteraemia, particularly in patients with advanced age and comorbidities. Direct inoculation of joint fluid into blood culture medium BACTEC system increases the probability of microbiological diagnosis. The prognosis is usually favourable if the disease is promptly recognized and treated (antibiotic therapy combined with joint drainage).

Neuroarthropathy secondary to transthyretin amyloidosis (ATTR V30M).

In this article we report the case of a 46-years-old Portuguese woman admitted in our orthopaedic ward with right knee pain. Radiological findings were consistent with neuroarthropathy. After exclusion of the most common causes of polyneuropathy, Familial amyloid polyneuropathy (FAP) was diagnosed by the discovery of a mutation V30M on chromosome 18 by polymerase chain reaction on a fibroblast culture of her skin biopsy. FAP is one of many aetiologies of polyneuropathy. Although a rare disease, genetic screening in selected populations makes early diagnosis and prompt treatment of asymptomatic family members readily available.

Forearm reconstruction with bone allograft following tumor excision: a series of 10 patients with a mean follow-up of 10 years.

BACKGROUND: After a tumor resection, the reestablishment of the bone continuity at the forearm remains a challenge for restoring the biomechanics of hand and elbow. Bone allograft might be one option to consider amongst other suitable alternatives but there are insufficient data available to substantiate its value. PATIENTS AND METHODS: We retrospectively investigated a series of 10 consecutive patients that had presented a bone tumor at the forearm. After bone excision, the segmental loss was replaced either by a bone allograft or an osteochondral allograft. Patients were reviewed clinically and with radiographs. RESULTS: The mean follow-up was 110 ± 99 months. Fracture of the allograft was the most prevalent complication occurring in four patients, mainly in the osteoarticular group. Four patients were surgically revised: two of them had a fracture of the allograft that required a new one, another one had a painful stiff wrist requiring removal of the allograft and arthrodesis with autograft and the fourth one had a non-union of an intercalary allograft that was treated by a distal ulnar joint resection. Intercalary allograft had fewer complications than osteoarticular allografts and they had a better functional MSTS score with an average of 79% of a normal function compared to osteoarticular allografts with an average score of 62%. There was no infection. At the latest follow-up, one reconstruction of the forearm with an allograft failed and concerned the distal radius joint. DISCUSSION: A bone allograft when available can be considered as one amongst other suitable options for the reconstruction of the forearm skeleton.

Added value of pharmacist-acquired drug histories in an orthopaedic ward.

In Belgian hospitals, drug histories of patients taken on admission are generally collected by medical trainees, physicians and nurses. As errors in drug histories may lead to medication errors and adverse drug events, we aimed at comparing the data obtained by a clinical pharmacist with those obtained by the nurses in a surgical orthopaedic ward. In this four months study, 50 patients, with a mean age of 66 years, were included. Out of these 50 drug histories, 107 differences were found when comparing the data gathered by the nurses with the data of the pharmacist. On average, there were 2.1 discrepancies per patient. Omission of a drug and incorrect or unknown dose accounted for 80.3% of the discrepancies, while allergy and/or intolerance, incorrect frequency and addition of a drug accounted for respectively 11.2%, 4.8% and 3.7%. Interestingly, six drug categories represented almost 55% of the drug-related discrepancies.These were, in order of importance: anxiolytic and neuroleptics, antacids and proton pump inhibitors (PPI's), painkillers, antidepressants, aspirin and eye drops. Finally, 27% of the discrepancies concerned "over the counter" drugs. From this study we were able to conclude that the clinical pharmacist performed more complete and more accurate drug histories than nurses in the surgical orthopaedic care unit, especially in patients taking multiple drugs. These results suggest that drug histories taken by a pharmacist may lead to a reduction of potential adverse drug events during hospitalisation.

European quality system for tissue banking.

AIM: The aims of this project were to analyze the factors that influence quality and safety of tissues for transplantation and to develop the method to ensure standards of quality and safety in relation to tissue banking as demanded by European Directive 2004/23/EC and its technical annexes. It is organized in 4 Working Groups, the objectives of each one being focused in a specific area. STANDARDS: The Guide of Recommendations for Tissue Banking is structured into 4 parts: (1) quality systems that apply to tissue banking and general quality system requirements, (2) regulatory framework in Europe, (3) standards available, and (4) recommendations of the fundamental quality and safety keypoints. REGISTRY: This Working Group handled design of a multinational musculoskeletal tissue registry prototype. TRAINING: This Working Group handled design and validation of a specialized training model structured into online and face-to-face courses. The model was improved with suggestions from students, and 100% certification was obtained. AUDIT: The Guide for Auditing Tissue Establishments provides guidance for auditors, a self-assessment questionnaire, and an audit report form. The effectiveness and sustainability of the outputs were assessed. Both guides are useful for experienced tissue establishments and auditors and also for professionals that are starting in the field. The registry prototype proves it is possible to exchange tissues between establishments throughout Europe. The training model has been effective in educating staff and means having professionals with excellent expertise. Member states could adapt/adopt it. The guides should be updated periodically and perhaps a European organization should take responsibility for this and even create a body of auditors.