Low back pain (LBP) is the main cause of disability worldwide and is primarily triggered by intervertebral disc degeneration (IDD). Although several treatment options exist, no therapeutic tool has demonstrated to halt the progressive course of IDD. Therefore, several clinical trials are being conducted to investigate different strategies to regenerate the intervertebral disc, with numerous studies not reaching completion nor being published. The aim of this study was to analyze the publication status of clinical trials on novel regenerative treatments for IDD by funding source and identify critical obstacles preventing their conclusion.

Prospective clinical trials investigating regenerative treatments for IDD and registered on ClinicalTrials.gov were included. Primary outcomes were publication status and investigational treatment funding. Fisher's exact test was utilized to test the association for categorical variables between groups.

25 clinical trials were identified. Among these, only 6 (24%) have been published. The most common source of funding was university (52%), followed by industry (36%) and private companies (12%). Investigational treatments included autologous (56%) or allogeneic (12%) products alone or in combination with a carrier or delivery system (32%). The latter were more likely utilized in industry or privately funded studies (Fig. 1, p=0.0112). No significant difference was found in terms of funding regarding the publication status of included trials (Table 1, p=0.9104).

Most clinical trials investigating regenerative approaches for the treatment of IDD were never completed nor published. This is likely due to multiple factors, including difficult enrollment, high dropout rate, and publication bias³. More accurate design and technical support from stakeholders and clinical research organization (CROs) may likely increase the quality of future clinical trials in the field.

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Clinical translation of MSC therapies in orthopaedics has been hampered by heterogeneity and a lack of standardised and validated testing protocols for quality assurance. Although minimal criteria have been proposed¹, it is apparent that these do not predict performance in vivo. We used a combinatorial antibody profiling tool to probe the surface immunophenotype of human bone marrow derived MSCs and used this to define new marker panels. Cells were cultured from three marrow donors using specified expansion conditions and probed by high throughput flow cytometry using a panel of 230 antibodies. Analysis of expression of the surface proteins revealed significant variation in response to culture conditions and considerably less variation between donors. Of the panel of 230 markers 107 were negative, 24 had high expression in all samples, 1 had low expression and 98 displayed significant differences between cell preparations. Cluster analyses revealed that marker expression in one culture condition varied considerably from the other two. Phenotypic characterization of the cell preparations, assessed by analysis of differentiation propensity, showed similar patterns of variability between these samples. This suggests that the selected panel may be used as phenotypic MSC markers. Ongoing work involves the generation of novel antibody arrays which will be used as quality tests in a manufacturing environment. These tests will be used for in-process and product release applications for enhanced cell manufacturing and improved clinical outcomes.

We performed this systematic overview on the overlapping meta-analyses that analyzed autologous platelet-rich plasma (PRP) as an adjuvant in the repair of rotator cuff tears and identify the studies which provide the current best evidence on this subject and generate recommendations for the same. We conducted independent and duplicate electronic database searches in PubMed, Web of Science, Scopus, Embase, Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effects on September 8, 2021, to identify meta-analyses that analyzed the efficacy of PRP as an adjuvant in the repair of rotator cuff tears. Methodological quality assessment was made using Oxford Levels of Evidence, AMSTAR scoring, and AMSTAR 2 grades and used the Jadad decision algorithm to generate recommendations. 20 meta-analyses fulfilling the eligibility criteria were included. The AMSTAR scores of the included studies varied from 6–10 (mean:7.9). All the included studies had critically low reliability in their summary of results due to their methodological flaws according to AMSTAR 2 grades. The initial size of the tear and type of repair performed do not seem to affect the benefit of PRPs. Among the different preparations used, leucocyte poor (LP)-PRP possibly offers the greatest benefit as a biological augment in these situations. Based on this systematic overview, we give a Level II recommendation that intra-operative use of PRPs at the bone-tendon interface can augment the healing rate, reduce re-tears, enhance the functional outcomes and mitigate pain in patients undergoing arthroscopic rotator cuff repair

Primary malignant bone and soft tissue tumours often occur in the lower extremities of active individuals including children, teenagers and young adults. Survivors routinely face long-term physical disability. Participation in sports is particularly important for active young people but the impact of sarcoma treatment is not widely recognised and clinicians may be unable to provide objective advice about returning to sports. We aimed to identify and summarise the current evidence for involvement in sports following treatment of lower limb primary malignant bone and soft tissue tumours. A comprehensive search strategy was used to identify relevant studies combining the main concepts of interest: (1) Bone/Soft Tissue Tumour, (2) Lower Limb, (3) Surgical Interventions and (4) Sports. Studies were selected according to eligibility criteria with the consensus of three authors. Customised data extraction and quality assessment tools were used. 22 studies were selected, published between 1985 – 2020, and comprising 1005 patients. Fifteen studies with data on return to sports including 705 participants of which 412 (58.4%) returned to some form of sport at a mean follow-up period of 7.6 years. Four studies directly compared limb sparing and amputation; none of these were able to identify a difference in sports participation or ability. Return to sports is important for patients treated for musculoskeletal tumours, however, there is insufficient published research to provide good information and support for patients. Future prospective studies are needed to collect better pre and post-treatment data at multiple time intervals and validated clinical and patient sports participation outcomes such as type of sports participation, level and frequency and a validated sports specific outcome score, such as UCLA assessment. In particular, more comparison between limb sparing and amputation would be welcome

Several emerging reports suggest an important involvement of the hindfoot alignment in the outcome of knee osteotomy. At present, studies lack a comprehensive overview. Therefore, we aimed to systematically review all biomechanical and clinical studies investigating the role of the hindfoot alignment in the setting of osteotomies around the knee. A systematic literature search was conducted on multiple databases combining “knee osteotomy” and “hindfoot/ankle alignment” search terms. Articles were screened and included according to the PRISMA guidelines. A quality assessment was conducted using the Quality Appraisal for Cadaveric Studies (QUACS) - and modified methodologic index for non-randomized studies (MINORS) scales. Three cadaveric, fourteen retrospective cohort and two case-control studies were eligible for review. Biomechanical hindfoot characteristics were positively affected (n=4), except in rigid subtalar joint (n=1) or talar tilt (n=1) deformity. Patient symptoms and/or radiographic alignment at the level of the hindfoot did also improve after knee osteotomy (n=13), except in case of a small pre-operative lateral distal tibia- and hip knee ankle (HKA) angulation or in case of a large HKA correction (>14.5°). Additionally, a pre-existent hindfoot deformity (>15.9°) was associated with undercorrection of lower limb alignment following knee osteotomy. The mean QUACS score was 61.3% (range: 46–69%) and mean MINORS score was 9.2 out of 16 (range 6–12) for non-comparative and 16.5 out of 24 (range 15–18) for comparative studies. Osteotomies performed to correct knee deformity have also an impact on biomechanical and clinical outcomes of the hindfoot. In general, these are reported to be beneficial, but several parameters were identified that are associated with newly onset – or deterioration of hindfoot symptoms following knee osteotomy. Further prospective studies are warranted to assess how diagnostic and therapeutic algorithms based on the identified criteria could be implemented to optimize the overall outcome of knee osteotomy. Remark: Aline Van Oevelen and Arne Burssens contributed equally to this work

Applications of weightbearing computed tomography (WBCT) imaging in the foot and ankle have emerged over the past decade. However, the potential diagnostic benefits are scattered across the literature, and a concise overview is currently lacking. Therefore, we aimed to systematically review all reported diagnostic applications per anatomical region in the foot and ankle. A systematic literature search was performed in the electronic databases PubMed, EMBASE, Cochrane Library, and Web of Science. Search terms consisted of “weightbearing/standing CT and ankle, hind-, mid- or forefoot”. English language studies analyzing the diagnostic applications of WBCT were included. Studies were excluded if they simulated weightbearing CT, described normal subjects, included cadaveric samples or samples were case reports. The modified Methodological Index for Non-Randomized Studies (MINORS) was applied for quality assessment. The added value was defined as the review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and registered in the Prospero database (CRD42019106980). A total of 48 studies (prospective N=8, retrospective N=36, cohort study N=1, diagnostic N=2, prognostic comparative study N=1) were found to be eligible for review. The following diagnostic applications were identified per anatomical area in the foot: ankle (osteoarthritis N=5, ligament injury N=6); hindfoot (deformity N=9); midfoot (Lisfranc injury N=2, flatfoot deformity N=13, osteoarthritis N=1); forefoot (hallux valgus N=12). The identified studies contained diagnostic applications that could not be used on plain radiographs. The mean MINORS equaled 10.1 on a total of 16 (range: 8 to 12). Diagnostic applications of weightbearing CT imaging are most frequently studied in hindfoot deformity, but other area's areas are on the rise. Post-processing of images was identified as the main added value compared to WBRX. However, the findings should be interpreted with caution as the average quality score was moderate. Therefore, future prospective studies are warranted to consolidate the role of WBCT in diagnostic and therapeutic algorithms

Intraoperative fractures although rare are one of the complications known to occur while performing a total hip arthroplasty (THA). However, due to lower incidence rates there is currently a gap in this area of literature that systematically reviews this important issue of complications associated with THA. Method: We looked into Electronic databases including PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), the archives of meetings of orthopaedic associations and the bibliographies of included articles and asked experts to identify prospective studies, published in any language that evaluated intra-operative fractures occurring during total hip arthroplasty from the year 1950-2020. The screening, data extraction and quality assessment were carried out by two researchers and if there was any discrepancy, a third reviewer was involved. Fourteen studies were identified. The reported range of occurrence of fracture while performing hip replacement surgery was found to be 0.4-7.6%. Major risk factors identified were surgical approaches, Elderly age, less Metaphyseal-Diaphyseal Index score, change in resistance while insertion of the femur implants, inexperienced surgeons, uncemented femoral components, use of monoblock elliptical components, implantation of the acetabular components, patients with ankylosing spondylitis, female gender, uncemented stems in patients with abnormal proximal femoral anatomy and with cortices, different stem designs, heterogeneous fracture patterns and toothed design. Intraoperative fractures during THA were managed with cerclage wire, femoral revision, intramedullary nail and cerclage wires, use of internal fixation plates and screws for management of intra operative femur and acetabular fractures. The main reason for intraoperative fracture was found to be usage of cementless implants but planning and timely recognition of risk factors and evaluating them is important in management of intraoperative fractures. Adequate surgical site exposure is critical especially during dislocation of hip, reaming of acetabulum, impaction of implant and preparing the femoral canal for stem insertion. Eccentric and increased reaming of acetabulum to accommodate a larger cup is to be avoided, especially in females and elderly patients as the acetabulum is thinner. However, this area requires more research in order to obtain more evidence on effectiveness, safety and management of intraoperative fractures during THA

Introduction and Objective. Evidence in literature is contradicting regarding outcomes of total knee arthroplasty (TKA) in post-traumatic osteoarthritis (PTOA) and whether they are inferior to TKA in primary osteoarthritis (OA). The aim of this review was to find out if any difference exists in the results of TKA between the two indications. Materials and Methods. The electronic databases MEDLINE, EMBASE, The Cochrane Collaboration, and PubMed were searched and screened in duplicate for relevant studies. The selected studies were further subjected to quality assessment using the modified Coleman method. The primary outcome measure was patient reported outcome, and secondary outcome measures were infection, revision, stiffness, and patella tendon rupture. Results. A total of 18 studies involved 1129 patients with a mean age of 60.6 years (range 45.7–69) and follow up of 6.3 years. The time interval from index injury to TKA was 9.1 years. Knee Society Score (KSS) in PTOA reported in 12/18 studies showed functional improvement from 42.5 to 70 post-TKA exceeding minimally clinically important difference. In TKA for primary OA vs PTOA, deep peri-prosthetic joint infection (PJI) was reported in 1.9% vs 5.4% of patients, whilst revision of prosthesis at an average of 6 years post-operatively was performed in 2.6 vs 9.7% of patients. Conclusions. TKA is a successful treatment option for PTOA. However, the risk of significant complications like PJI and implant failure requiring revision is higher than primary OA cases. Patients should be counselled about those risks. Further well-designed comparative cohort-matched studies are needed to compare outcomes between the two populations

Telemedicine is the delivery of healthcare from a remote location using integrated computer/communication technology. This systematic review aims to explore evidence for telemedicine in orthopaedics to determine its advantages, validity, effectiveness and utilisation particularly during our current pandemic where patient contact is limited. Databases of PubMed, Scopus and CINHAL were systematically searched and articles were included if they involved any form of telephone or video consultation in an orthopaedic population. Findings were synthesised into four themes: patient/clinician satisfaction, accuracy and validity of examination, safety and patient outcomes and cost effectiveness. Quality assessment was undertaken using Cochrane and Joanna Briggs Institute appraisal tools. Twenty studies were included consisting of nine RCTs across numerous orthopaedic subspecialties including fracture care, elective orthopaedics and oncology. Studies revealed high patient satisfaction with telemedicine for convenience, less waiting and travelling time. Telemedicine was cost effective particularly if patients had to travel long distances, required hospital transport or time off work. No clinically significant differences were found in patient examination nor measurement of patient reported outcome measures. Telemedicine was reported to be a safe method of consultation. However, studies were of variable methodological quality with selection bias. In conclusion, evidence suggests that telemedicine in orthopaedics can be safe, cost effective, valid in clinical assessment with high patient/clinician satisfaction. Further work with high quality RCTs is required to elucidate long term outcomes. This systematic review presents up-to-date evidence on the use of telemedicine and provides data for organisations considering its use in the current COVID-19 pandemic and beyond

The relevance of physical activity (PA) for general health and the value of assessing PA in the free-living environment especially for assessing orthopaedic conditions and outcome are discussed. Available methods for assessing PA such as self-reports, trackers, phone apps and clinical grade monitors are introduced. An overview of devices such as accelerometers for research quality assessments is given and aspects for choosing them such as wear location, usability or study population are reviewed. Basic principles to derive mobility parameters from the PA related sensor signals are presented. The symposium explains mobility parameters, their types, definitions, validity, analysis and those with particular relevance to assess orthopaedic conditions. The application of activity monitors is orthopaedic patient studies is demonstrated in various examples such as knee and hop osteoarthritis and total joint arthroplasty, in frail elderly subjects at fall risk or patients with shoulder pathologies

Background. Despite arthroscopy being the gold standard for long head of biceps pathology, the literature is seemingly lacking in any critical appraisal or validation to support its use. The aim of this study was to evaluate its appropriateness as a benchmark for diagnosis. The objectives were to evaluate whether the length of the tendon examined at arthroscopy allows visualisation of areas of predilection of pathology and also to determine the rates of missed diagnoses when compared to an open approach. Methods. A systematic review of cadaveric and clinical studies was performed. The search strategy was applied to Medline, PubMed and Google Scholar databases. All relevant articles were included. Critical appraisal of clinical studies was performed using a validated quality assessment scale. Results. Six articles were identified for inclusion in the review. This included both clinical and cadaveric studies. The overall population comprised 25 cadaveric specimens and 575 patients. Cadaveric studies showed that the use of a hook probe allowed arthroscopic visualisation of between 28% and 48% of the overall length of the LHB. In the clinical series the rate of missed diagnoses at arthroscopy when compared to open exploration ranged between 33% and 49%. Conclusions. The standard technique of pulling the LHB tendon into the joint at glenohumeral arthroscopy provides only limited excursion and does not allow visualisation of areas of predilection of pathology. This is confirmed by an extremely high rate of missed diagnoses when comparing arthroscopy to open exploration. It is important that clinicians recognise that a “normal” arthroscopic examination of the LHB tendon does not exclude pathology and that published literature reporting sensitivities and specificities for physical examination and imaging tests based on arthroscopy as a gold standard are invalid. Level of evidence. IIa – systematic review of cohort studies. Conflict of Interests. The authors confirm that they have no relevant financial disclosures or conflicts of interest. Ethical approval was not sought as this was a systematic review

Background. Distal radius fractures are common injuries but no clear consensus regarding optimal management of unstable fractures exists. Open reduction and internal fixation with volar plates is an increasingly popular but the associated complication rate can be 10%. Intramedullary nails are an alternative offering the potential advantages of reduced risk of tendon injury and intra-articular screw penetration. This article systematically reviews the published literature evaluating the biomechanics, outcomes and complications of intramedullary nails in the management of distal radius fractures. Methods. A systematic review of Medline and EMBASE databases was performed for studies reporting the biomechanics, functional outcome or complications following intramedullary nailing of distal radius fractures. Critical appraisal was performed with respect to validated quality assessment scales. Results. 16 studies were included for review. The biomechanical studies concluded that intramedullary nails had at least comparable strength to locking plates. The clinical studies reported that IM nailing was associated with comparable ROM, functional outcome and grip strength to alternative fixation techniques. However, the mean complication rate was 17.6% (range 0 to 50%) with the most common complication being neurapraxia of the superficial radial nerve in 9.5%. Conclusion. This systematic review of pooled data from published series has shown that IM nailing can give comparable clinical results to current treatment modalities in extra-articular and simple intra-articular distal radius fractures. However the evidence is insufficient to determine whether IM nailing has any clinically important advantage over well-established alternatives. The complication rate reported is higher than that in contemporary studies for volar plating and this raises concerns about the role of this technique particularly when comparative studies have failed to show any major advantage to its use. Further adequately powered RCTs comparing the technique to both volar plates and percutaneous wire fixation are required. Level of evidence. IIa – systematic review of cohort studies. Conflict of Interests. The authors confirm that they have no relevant financial disclosures or conflicts of interest. Ethical approval was not sought as this was a systematic review

Introduction. Achilles tendinopathy (AT) is a highly prevalent injury in athletes and non-athletes with an unknown aetiology. Genetic risk factors have been a recent focus of investigation. The aim of this systematic review was to determine which loci have been linked with mid-portion AT and could potentially be used as biomarkers in tendinopathy risk models or as preventative or therapeutic targets. Materials and Methods. Eight electronic bibliographic databases were searched from inception to April 2015 for cross-sectional, prospective cohort and case-control studies that included empirical research investigating genes associated with mid-portion AT. Potential publications were assessed by two independent reviewers (AAC and PRJ) for inclusion and quality. Quality was evaluated using a validated scale. Results. Twelve candidate gene studies and three pathway-based genetic association studies that investigated genetic risk factors for AT were identified. According to Ariëns's criteria, there was strong evidence for the COL5A1 gene. There was some evidence for 6 of the other genes investigated: COL5A3, TNC, CASP8, MIR608, GDF5, MMP3 and TIMP2 genes. There was inconclusive evidence for the following genes: COL3A1, COL5A2, COL11A1, COL11A2, COL12A1, COL1A1, COL27A1, COL14A1, COMP, THBS2, ADAMTS2, ADAMTS5, ADAMTS14, ADAM12, TGFβ1, IL-1β, IL-1RN, IL-6, NOS2 and NOS3. There was some evidence for combinations of functional variants of different genes and pseudohaplotypes constructed from many functional variants. The quality of included studies varied (3/9 to 7/9), and the average quality assessment score was 5.5/9 (61%). Discussion. There are genetic differences between subjects with and without AT. To further elucidate these findings, prospective studies are needed to investigate the increased risk associated with specific genetic findings. Modifying training loads or preventative exercise may be used to mitigate increased risk, although it needs to be highlighted that a genetic association does not necessarily mean an individual will develop Achilles tendinopathy. Gene therapy may have a role in tendon healing, but further research is necessary to develop risk models and establish the most advantageous genes to transfer

Summary. Computer assisted surgery (CAS) during total knee arthroplasty (TKA) is known to improve prosthetic alignment in coronal and sagittal plane. In this systematic review, no evidence is found that CAS also improves axial component orientation when used during TKA. Introduction. Primary total knee arthroplasty (TKA) is a safe and cost-effective treatment for end-stage knee osteoarthritis. Correct prosthesis alignment is essential, since malpositioning of the prosthesis leads to worse functional outcome and increased wear, which compromises survival of the prosthesis. Computer assisted surgery (CAS) has been developed to enhance prosthesis alignment during TKA. CAS significantly improves postoperative coronal and sagittal alignment compared to conventional TKA. However, the influence of CAS on rotational alignment is a matter of debate. Therefore purpose of this review is to assess published evidence on the influence of CAS during TKA on postoperative rotational alignment. Patients and Methods. This review was performed according to the PRISMA Statement. An electronic literature search was performed in Pubmed, Medline and Embase on studies published between 1991 and April 2013. Studies were included when rotational alignment following imageless CAS-TKA was compared to rotational alignment following conventional TKA. At least one of the following outcome measures had to be assessed: 1) rotational alignment of the femoral component, 2) rotational alignment of the tibial component, 3) tibiofemoral mismatch, 4) the amount of rotational outliers of the femoral component, 5) the amount of rotational outliers of the tibial component. Study selection was performed in two stages and data extraction and methodological quality assessment was conducted independently by two reviewers. Standardized mean difference (SMD) with 95% confidence interval (95% CI) was calculated for continuous variables. The SMDs were interpreted according to Cohen: an SMD of 0.2–0.4 was considered a small effect; 0.5–0.7 was considered moderate; and ≥ 0.8 was considered a large effect. For the comparison of the amount of outliers for femoral and tibial component rotation, the Odds ratio (OR) and 95% CI was calculated. The OR represents the odds of outliers occurring in the CAS group compared with the conventional group. An OR of < 1 favors the CAS group. The OR is considered statistically significant when the 95% CI does not include the value of 1. Results. Seventeen studies met the inclusion criteria. One study was considered of high, 15 studies of medium and one study of low methodological quality. SMD for rotation of the femoral component was −0.07 (−0.19–0.04). For rotation of the tibial component, the SMD was 0.11 (−0.01–0.24). Regarding tibiofemoral mismatch, the SMD was −0.27 (−0.57–0.02). For femoral outliers, the OR was 1.05 (0.78–1.43) and for tibial outliers the OR was 1.12 (0.86–1.47). Discussion / Conclusion. Results of this review show no evidence that CAS-TKA leads to better rotational alignment of the femoral or tibial component or tibiofemoral mismatch. Also no evidence was found that CAS results in a decrease of the amount of outliers regarding femoral or tibial component orientation. However, these conclusions have to be interpreted with caution. The number of included studies was low and strong heterogeneity existed between the studies. Of the 17 included studies, only one study was considered of high methodological quality. Moreover, different methods for assessing tibial component rotation have been used in the studies included

Aims

Animal models have been developed that allow simulation of post-traumatic joint contracture. One such model involves contracture-forming surgery followed by surgical capsular release. This model allows testing of antifibrotic agents, such as rosiglitazone.

Objectives

To review the systemic impact of smoking on bone healing as evidenced within the orthopaedic literature.

Objectives

We aimed first to summarise minimal clinically important differences (MCIDs) after total hip (THR) or knee replacement (TKR) in health-related quality of life (HRQoL), measured using the Short-Form 36 (SF-36). Secondly, we aimed to improve the precision of MCID estimates by means of meta-analysis.