Comparing a Sensor for Movement Assessment with Traditional Physiotherapeutic Assessment Methods in Patients after Knee Surgery-A Method Comparison and Reproducibility Study.

Wearable sensors offer the opportunity for patients to perform a self-assessment of their function with respect to a variety of movement exercises. Corresponding commercial products have the potential to change the communication between patients and physiotherapists during the recovery process. Even if they turn out to be user-friendly, there remains the question to what degree the numerical results are reliable and comparable with those obtained by assessment methods traditionally used. To address this question for one specific recently developed and commercially available sensor, a method comparison study was performed. The sensor-based assessment of eight movement parameters was compared with an assessment of the same parameters based on test procedures traditionally used. Thirty-three patients recovering after arthroscopic knee surgery participated in the study. The whole assessment procedure was repeated. Reproducibility and agreement were quantified by the intra class correlation coefficient. The height of a one-leg vertical jump and the number of side hops showed high agreement between the two modalities and high reproducibility (ICC > 0.85). Due to differences in the set-up of the assessment, agreement could not be achieved for three mobility parameters, but even the correlation was only fair (r < 0.5). Knee stability showed poor agreement. Consequently, the use of the sensor can currently only be recommended for selected parameters. The variation in degree of agreement and reproducibility across different parameters clearly indicate the need for developing corresponding guidance for each new sensor put onto the market.

In Vitro and Ectopic In Vivo Studies toward the Utilization of Rapidly Isolated Human Nasal Chondrocytes for Single-Stage Arthroscopic Cartilage Regeneration Therapy.

Nasal chondrocytes (NCs) have a higher and more reproducible chondrogenic capacity than articular chondrocytes, and the engineered cartilage tissue they generate in vitro has been demonstrated to be safe in clinical applications. Here, we aimed at determining the feasibility for a single-stage application of NCs for cartilage regeneration under minimally invasive settings. In particular, we assessed whether NCs isolated using a short collagenase digestion protocol retain their potential to proliferate and chondro-differentiate within an injectable, swiftly cross-linked and matrix-metalloproteinase (MMP)-degradable polyethylene glycol (PEG) gel enriched with human platelet lysate (hPL). NC-hPL-PEG gels were additionally tested for their capacity to generate cartilage tissue in vivo and to integrate into cartilage/bone compartments of human osteochondral plugs upon ectopic subcutaneous implantation into nude mice. NCs isolated with a rapid protocol and embedded in PEG gels with hPL at low cell density were capable of efficiently proliferating and of generating tissue rich in glycosaminoglycans and collagen II. NC-hPL-PEG gels developed into hyaline-like cartilage tissues upon ectopic in vivo implantation and integrated with surrounding native cartilage and bone tissues. The delivery of NCs in PEG gels containing hPL is a feasible strategy for cartilage repair and now requires further validation in orthotopic in vivo models.

Engineered nasal cartilage for the repair of osteoarthritic knee cartilage defects.

Osteoarthritis (OA) is the most prevalent joint disorder, causing pain and disability predominantly in the aging population but also affecting young individuals. Current treatments are limited to use of anti-inflammatory drugs to alleviate symptoms or degenerated joint replacement by a prosthetic implant at the end stage of the disease. We hypothesized that degenerative cartilage defects can be treated using nasal chondrocyte­based tissue-engineered cartilage (N-TEC). We demonstrate that N-TEC maintained cartilaginous properties when exposed in vitro to inflammatory stimuli found in osteoarthritic joints and favorably altered the inflammatory profile of cells from osteoarthritic joints. These effects were at least partially mediated by down-regulation of the WNT (wingless/integrated) signaling pathway through sFRP1 (secreted frizzled-related protein-1). We further report that N-TEC survive and engraft in vivo in ectopic mouse models reproducing a human osteochondral OA tissue environment, as well as in sheep articular cartilage defects that mimic degenerative settings. Last, we tested the safety of autologous N-TEC for the treatment of osteoarthritic cartilage defects in the knees of two patients with advanced OA (Kellgren and Lawrence grades 3 and 4) who were otherwise considered for unicondylar knee arthroplasty. No adverse reactions were recorded, and patients reported reduced pain as well as improved joint function and life quality 14 months after surgery. Together, our findings indicate that N-TEC can directly contribute to cartilage repair in osteoarthritic joints. A suitably powered clinical trial is now required to assess its efficacy in the treatment of patients with OA.

Kinesiotaping for postoperative oedema - what is the evidence? A systematic review.

BACKGROUND: Postoperative oedema is a common condition affecting wound healing and function. Traditionally, manual lymphatic drainage is employed to reduce swelling. Kinesiotaping might be an alternative resource-sparing approach. This article explores current evidence for the effectiveness of kinesiotaping for the reduction of oedema in the postoperative setting. METHODS: A systematic literature search was performed on the basis of five databases (Pubmed, CINAHL, Embase, Cochrane Library, and Clinicaltrials.gov) for studies published between January 2000 and October 2019.Only prospective controlled trials were included. Case studies, uncontrolled case series, studies on oedema caused by other etiologies than by surgery, as well as studies on malignant disease related oedema (especially breast cancer related oedema) were excluded.Articles were screened by title, abstract, and full text and the references were searched for further publications on the topic. A narrative and quantitative (using STATA) analysis was performed. RESULTS: One thousand two hundred sixty-three articles were screened, twelve were included in the analysis. All studies evaluated either oedema after extremity surgery or maxillofacial interventions, and showed relevant methodological flaws. Only three studies employed an active comparator. Of the twelve included studies ten found positive evidence for kinesiotape application for the reduction of swelling and beneficial effects on secondary outcome parameters such as pain and patient satisfaction. The available trials were heterogenic in pathology and all were compromised by a high risk of bias. CONCLUSION: There is some evidence for the efficacy of kinesiotaping for the treatment of postoperative oedema. This evidence is, however, not yet convincing given the limitations of the published trials. Methodologically sound comparison to standard of care or an active comparator is indispensable for an evaluation of effectiveness. In addition, assessments of patient comfort and cost-benefit analyses are necessary to evaluate the potential relevance of this novel technique in daily practice. SYSTEMATIC REVIEW REGISTRATION NUMBER: International prospective register of systematic reviews (PROSPERO) ID 114129).

High rate of maintaining self-dependence and low complication rate with a new treatment algorithm for proximal humeral fractures in the elderly population.

BACKGROUND: We modified our treatment algorithm for proximal humeral fractures in elderly patients in 2013 to a more conservative approach avoiding locking plates. This study assesses the impact of this change on patient self-dependence. METHODS: We carried out an observational comparative study including both retrospectively and prospectively collected data. For the former, 147 isolated proximal humeral fracture patients older than 65 years were treated between 2011 and 2013 at our hospital and included in a historical group. The revised treatment algorithm was applied in a similar non-concurrent, comparative patient group (n = 160) prospectively enrolled between 2015 and 2017. The primary outcome was any loss of self-dependence, with secondary outcomes including documentation of shoulder functional scores, quality of life, and adverse events. RESULTS: Historical and prospective patients had similar baseline characteristics. Nonoperative treatment was performed in 53 historical patients (36%) and 83 prospective patients (78%). Prospective patients were 1.6 times less likely to lose some level of self-dependence (risk ratio, 0.62; 95% confidence interval, 0.25-1.5; P = .292), and the local adverse event risk dropped from 12.2% to 5.7% (P = .078). Mean shoulder function and quality of life were similar between the 2 groups. CONCLUSION: By applying our revised algorithm, a higher proportion of elderly patients maintained their premorbid level of self-dependence and returned to their previous social environment.

Mid-term results of minimally invasive deltoid-split versus standard open deltopectoral approach for PHILOS™ (proximal humeral internal locking system) osteosynthesis in proximal humeral fractures.

PURPOSE: Only a few reports compare the mid- and long-term outcome of the minimally invasive deltoid split (MIDS) with the classic anterior deltopectoral (DP) approach for osteosynthesis in proximal humeral fractures. This study compared the mid-term functional and the radiological results in patients with proximal humeral fractures undergoing osteosynthesis with the proximal humeral internal locking system (PHILOS™). METHODS: All patients undergoing osteosynthesis between 2008 and 2015 were clinically and radiologically examined with a minimal follow-up period of 1 year. Functional outcomes were analyzed using the DASH- and Constant Shoulder Scores (CSS). Radiological results were analyzed using a newly developed score. RESULTS: Thirty-nine patients underwent PHILOS™ osteosynthesis with the MIDS and twenty-three with the DP approach. Follow-up time was 41 months in the MIDS group and 62 months in the DP group, respectively. The median CSS was similar with 79 points in the MIDS group and 82 points in the DP group (p = 0.17). The MIDS group showed a significant lower power measurement in the CSS. In four-part fractures, a substantially lower CSS in absolute numbers in the MIDS group was detected. The median DASH score was 26.7 points in the MIDS group and 25.8 points in the DP group (p = 0.48). There was no difference in the radiological score. More patients with partial avascular necrosis (AVN) were found in the MIDS group, most with three- and four-part fractures. However, this was not statistically significant. Morbidity was similar between groups. CONCLUSION: The results of the two surgical approaches are statistically comparable. Some differences such as a lower power measurement in the MIDS group, a higher partial AVN frequency and more plate removals are observed. In four-part fractures, the CSS was lower in the MIDS compared to the DP cohort. The MIDS technique might not be a solution for all fracture types, and the surgeon should be careful to analyze the morphology of the fracture before deciding upon the approach. Four-part fractures might be better treated with a DP approach.

Intra-individual comparison of human nasal chondrocytes and debrided knee chondrocytes: Relevance for engineering autologous cartilage grafts.

OBJECTIVE: Implantation of autologous chondrocytes for cartilage repair requires harvesting of undamaged cartilage, implying an additional joint arthroscopy surgery and further damage to the articular surface. As alternative possible cell sources, in this study we assessed the proliferation and chondrogenic capacity of debrided Knee Chondrocytes (dKC) and Nasal Chondrocytes (NC) collected from the same patients. METHODS: Matched NC and dKC pairs from 13 patients enrolled in two clinical studies (NCT01605201 and NCT026739059) were expanded in monolayer and then chondro-differentiated in 3D collagenous scaffolds in medium with or without Transforming Growth Factor beta 1 (TGFß1). Cell proliferation and amount of cartilage matrix production by these two cell types were assessed. RESULTS: dKC exhibited an inferior proliferation rate than NC, and a lower capacity to chondro-differentiate. Resulting dKC-grafts contained lower amounts of cartilage specific matrix components glycosaminoglycans and type II collagen. The cartilage forming capacity of dKC did not significantly correlate with specific clinical parameters and was only partially improved by medium supplemention with TGFß1. CONCLUSIONS: dKC exhibit a reproducibly poor capacity to engineer cartilage grafts. Our in vitro data suggest that NC would be a better suitable cell source for the generation of autologous cartilage grafts.

Routine patient surveys: Patients' preferences and information gained by healthcare providers.

BACKGROUND: Patient feedback after contact with a hospital is regarded as an important source of information for the improvement of local healthcare services. Routine patient surveys are in widespread use to obtain such feedback. While general principles for the composition of this kind of surveys have been described in the literature, it is unknown which method of contact and topics of feedback are important to patients in postcontact healthcare surveys. MATERIAL AND METHODS: We invited 2931 consecutive patients who had in- or outpatient contact with the Department of Orthopaedics and Traumatology at the University Hospital Basel to an anonymous survey. They were asked whether they were generally in favor of feedback surveys. They also had the opportunity to state their preferred form of contact (text message, app, email, online or letter) and provide up to three topics that they regarded as specifically important in patient surveys. RESULTS: A total of 745 patients participated in the survey (25.4%), of these 61.9% expressed the preference to be surveyed, and 69.1% selected `letter' as one of the preferred forms of contact. Favoring only `letter' contact increased substantially with age. Overall 54.6% of patients stated at least one topic that they wished to give feedback on. The most frequent topics were related to treatment and rather general aspects regarding staff and overall impression. The wish to include suggestions for improvements was rarely mentioned as specific topic. CONCLUSIONS: The majority of patients seem to be rather indifferent to the existence and content of patient surveys. They mention a wide range of topics from general to specific ones, but do not express interest in the opportunity to suggest changes. There is a need to effectively engage patients in healthcare planning using new approaches to obtain valuable feedback on patients' hospital stay and contact experiences. These new approaches should ideally be more informative and cost-effective than the current practice.

Tissue engineering for paediatric patients.

The effects of oncological treatment, congenital anomalies, traumatic injuries and post-infection damage critically require sufficient amounts of tissue for structural and functional surgical reconstructions. The patient’s own body is typically the gold standard source of transplant material, but in children autologous tissue is available only in small quantities and with severe morbidity at donor sites. Engineering of tissue grafts starting from a small amount of autologous material, combined with suitable surgical manipulation of the recipient site, is expected to enhance child and adolescent health, and to offer functional restoration for long-term wellbeing. Moreover, engineered tissues based on patient-derived cells represent invaluable models to investigate mechanisms of disease and to develop/test novel therapeutic approaches. In view of these great opportunities, here we introduce the currently limited successful implementation of tissue engineering in paediatric settings and discuss the open challenges in the field. A particular focus is on the specific needs and envisioned strategies in the areas of bone and osteochondral regeneration in children.

Handling of informed consent and patient inclusion in research with geriatric trauma patients - a matter of protection or disrespect?

BACKGROUND: Despite the aging of numerous societies and future health care challenges, clinical research in the elderly is underrepresented. The aim of this review was to analyze the current practice exemplary in gerontotraumatology and to discuss potential improvements. MATERIALS AND METHODS: A literature review was performed in 2016 based on a PubMed search for gerontotraumatologic studies published between 2005 and 2015. Trials were evaluated for methodology and ethical and age-related aspects. RESULTS: The search revealed 649 articles, 183 of which met the inclusion criteria. The age range for inclusion was heterogeneous; one-third of trials included patients <65 years and only 11% excluded very elderly. Seventy-four trials excluded patients with typical comorbidities, with 55% of these without stating scientific reasons. Frailty was assessed in 94 trials and defined as the exclusion criterion in 66 of them. Informed consent (IC) was reportedly obtained in 144 trials; descriptions of the IC process mostly remained vague. Substitute decision making was described in 19 trials; the consenting party remained unclear in 45 articles. Diagnosed dementia was a primary exclusion criterion in 31% of the trials. Seventeen trials assessed decisional capacity before inclusion, with six using specific assessments. CONCLUSION: Many trials in gerontotraumatology exclude relevant subgroups of patients, and thus risk presenting biased estimates of the relevant treatment effects. Exclusion based on age, cognitive impairment, or other exhaustive exclusion criteria impedes specific scientific progress in the treatment of elderly patients. Meaningful trials could profit from a staged, transparent approach that fosters shared decision making. Rethinking current policies is indispensable to improve treatment and care of elderly trauma patients and to protect study participants and researchers alike.

The association of surgical drains with surgical site infections - A prospective observational study.

BACKGROUND: Surgical drains are widely used despite limited evidence in their favor. This study describes the associations between drains and surgical site infections (SSI). METHODS: This prospective observational double center study was performed in Switzerland between February 2013 and August 2015. RESULTS: The odds of SSI in the presence of drains were increased in general (OR 2.41, 95%CI 1.32-4.30, p = 0.004), but less in vascular and not in orthopedic trauma surgery. In addition to the surgical division, the association between drains and SSI depended significantly on the duration of surgery (p = 0.01) and wound class (p = 0.034). Furthermore, the duration of drainage (OR 1.24, 95%CI 1.15-1.35, p < 0.001), the number (OR 1.74, 95%CI 1.09-2.74, p = 0.019) and type of drains (open versus closed: OR 3.68, 95%CI 1.88, 6.89, p < 0.001) as well as their location (overall p = 0.002) were significantly associated with SSI. CONCLUSIONS: The general use of drains is discouraged. However, drains may be beneficial in specific surgical procedures.

Daytime variation of perioperative myocardial injury in non-cardiac surgery and effect on outcome.

OBJECTIVE: Recently, daytime variation in perioperative myocardial injury (PMI) has been observed in patients undergoing cardiac surgery. We aim at investigating whether daytime variation also occurs in patients undergoing non-cardiac surgery. METHODS: In a prospective diagnostic study, we evaluated the presence of daytime variation in PMI in patients at increased cardiovascular risk undergoing non-cardiac surgery, as well as its possible impact on the incidence of acute myocardial infarction (AMI), and death during 1-year follow-up in a propensity score-matched cohort. PMI was defined as an absolute increase in high-sensitivity cardiac troponin T (hs-cTnT) concentration of ≥14 ng/L from preoperative to postoperative measurements. RESULTS: Of 1641 patients, propensity score matching defined 630 with similar baseline characteristics, half undergoing non-cardiac surgery in the morning (starting from 8:00 to 11:00) and half in the afternoon (starting from 14:00 to 17:00). There was no difference in PMI incidence between both groups (morning: 50, 15.8% (95% CI 12.3 to 20.3); afternoon: 52, 16.4% (95% CI 12.7 to 20.9), p=0.94), nor if analysing hs-cTnT release as a quantitative variable (median morning group: 3 ng/L (95% CI 1 to 7 ng/L); median afternoon group: 2 ng/L (95% CI 0 to 7 ng/L; p=0.16). During 1-year follow-up, the incidence of AMI was 1.2% (95% CI 0.4% to 3.2%) among morning surgeries versus 4.1% (95% CI 2.3% to 6.9%) among the afternoon surgeries (corrected HR for afternoon surgery 3.44, bootstrapped 95% CI 1.33 to 10.49, p log-rank=0.03), whereas no difference in mortality emerged (p=0.70). CONCLUSIONS: Although there is no daytime variation in PMI in patients undergoing non-cardiac surgery, the incidence of AMI during follow-up is increased in afternoon surgeries and requires further study. CLINICAL TRIAL REGISTRATION: NCT02573532;Results.

Rationale and methods of an observational study to support the design of a nationwide surgical registry: the MIDAS study.

BACKGROUND Surgical registries are becoming increasingly popular. In addition, Swiss legislation requires data on therapeutic outcome quality. The Swiss Association of Surgeons (Schweizerische Gesellschaft Chirurgie, SGC-SCC) has already agreed on a first minimum data set. However, in the long run the scope and content of the registry should be evidence-based and not only accepted by professional stakeholders. The MIDAS study aims at providing such evidence for the example population of patients undergoing emergency or elective hip surgery. Five relevant aspects are considered: (1) choice of instruments for assessing health related quality of life (HRQoL); (2) optimal time-point for assessment; (3) use of proxy assessments; (4) choice of pre-surgery risk factors; and (5) assessment of peri- and postoperative variables. METHODS MIDAS is a longitudinal observational multicentre study. All patients suffering from a femoral neck fracture or from arthritis of the hip joint with an indication for prosthetic joint replacement surgery will be offered participation. The study is based on a combination of routine data from clinical standard practice with specifically documented data to be reported by the treating clinician and data to be collected in cooperation with the patient ­ in particular patient-reported outcome measures (PROMs). The latter include the Health Utility Index Mark 3 (HUI3) and Euro-Qol-5D (EQ-5D) as generic instruments, Hip Disability and Osteoarthritis Outcome Score (HOOS) as a disease specific instrument for the assessment of HRQoL, and two performance-based functional tests. Data will be collected at baseline, during hospitalisation/at discharge and at three routine follow-up visits. All patients will be asked to name a person for assessing proxy-perceived HRQoL. DISCUSSION To the best of our knowledge, this is the first study explicitly addressing questions about the design of a national surgical registry in an empirical manner. The study aims at providing a scientific base for decisions regarding scope and content of a potential national Swiss surgical registry. We designed a pragmatic study to envision data collection in a national registry with the option of specifying isolated research questions of interest. One focus of the study is the use of PROMs, and we hope that our study and their results will inspire also other surgical registries to take this important step forward. Trial registration Registered at the "Deutsches Register Klinischer Studien (DRKS)", the German Clinical Trials Registry, since this registry meets the scope and methodology of the proposed study. Registration no.: DRKS00012991

Minimally invasive anterior muscle-sparing versus a transgluteal approach for hemiarthroplasty in femoral neck fractures-a prospective randomised controlled trial including 190 elderly patients.

BACKGROUND: The relevance of femoral neck fractures (FNFs) increases with the ageing of numerous societies, injury-related decline is observed in many patients. Treatment strategies have evolved towards primary joint replacement, but the impact of different approaches remains a matter of debate. The aim of this trial was to evaluate the benefit of an anterior minimally-invasive (AMIS) compared to a lateral Hardinge (LAT) approach for hemiarthroplasty in these oftentimes frail patients. METHODS: Four hundred thirty-nine patients were screened during the 44-months trial, aiming at the evaluation of 150 patients > 60 yrs. of age. Eligible patients were randomised using an online-tool with completely random assignment. As primary endpoint, early mobility, a predictor for long-term outcomes, was evaluated at 3 weeks via the "Timed up and go" test (TUG). Secondary endpoints included the Functional Independence Measure (FIM), pain, complications, one-year mobility and mortality. RESULTS: A total of 190 patients were randomised; both groups were comparable at baseline, with a predominance for frailty-associated factors in the AMIS-group. At 3 weeks, 146 patients were assessed for the primary outcome. There was a reduction in the median duration of TUG performance of 21.5% (CI [- 41.2,4.7], p = 0.104) in the AMIS-arm (i.e., improved mobility). This reduction was more pronounced in patients with signs of frailty or cognitive impairment. FIM scores increased on average by 6.7 points (CI [0.5-12.8], p = 0.037), pain measured on a 10-point visual analogue scale decreased on average by 0.7 points (CI: [- 1.4,0.0], p = 0.064). The requirement for blood transfusion was lower in the AMIS- group, the rate of complications comparable, with a higher rate of soft tissue complications in the LAT-group. The mortality was higher in the AMIS-group. CONCLUSION: These results, similar to previous reports, support the concept that in elderly patients at risk of frailty, the AMIS approach for hemiarthroplasty can be beneficial, since early mobilisation and pain reduction potentially reduce deconditioning, morbidity and loss of independence. The results are, however, influenced by a plethora of factors. Only improvements in every aspect of the therapeutic chain can lead to optimisation of treatment and improve outcomes in this growing patient population. TRIAL REGISTRATION: www.clinicaltrials.gov : NCT01408693 (registered August 3rd 2011).

Expansion of Bone Marrow Mesenchymal Stromal Cells in Perfused 3D Ceramic Scaffolds Enhances In Vivo Bone Formation.

Bone marrow-derived mesenchymal stromal cells (BMSC), when expanded directly within 3D ceramic scaffolds in perfusion bioreactors, more reproducibly form bone when implanted in vivo as compared to conventional expansion on 2D polystyrene dishes/flasks. Since the bioreactor-based expansion on 3D ceramic scaffolds encompasses multiple aspects that are inherently different from expansion on 2D polystyrene, we aimed to decouple the effects of specific parameters among these two model systems. We assessed the effects of the: 1) 3D scaffold vs. 2D surface; 2) ceramic vs. polystyrene materials; and 3) BMSC niche established within the ceramic pores during in vitro culture, on subsequent in vivo bone formation. While BMSC expanded on 3D polystyrene scaffolds in the bioreactor could maintain their in vivo osteogenic potential, results were similar as BMSC expanded in monolayer on 2D polystyrene, suggesting little influence of the scaffold 3D environment. Bone formation was most reproducible when BMSC are expanded on 3D ceramic, highlighting the influence of the ceramic substrate. The presence of a pre-formed niche within the scaffold pores had negligible effects on the in vivo bone formation. The results of this study allow a greater understanding of the parameters required for perfusion bioreactor-based manufacturing of osteogenic grafts for clinical applications.

Rivaroxaban for Thromboprophylaxis After Nonelective Orthopedic Trauma Surgery in Switzerland.

This study investigated the effectiveness and the outcomes of rivaroxaban vs the standard of care for venous thromboembolic prophylaxis in patients undergoing fracture-related surgery. A total of 413 patients undergoing fracture-related surgery from 9 Swiss orthopedic and trauma centers were enrolled. The authors selected the type of venous thromboembolic prophylaxis according to standardized medical practice at the participating centers before the inclusion of patients: 208 patients received rivaroxaban and 205 received the standard of care. Data on symptomatic thromboembolic and bleeding events, surgery-related complications, death, adverse events, time to mobilization, and hospital discharge were collected. Symptomatic thromboembolic events were reported in 1 patient (0.5%) and 2 patients (1.0%) and treatment-emergent major bleeding events were reported in 1 patient (0.5%) and 2 patients (1.0%) receiving rivaroxaban and the standard of care, respectively. The durations of hospital stay and venous thromboembolic prophylaxis were similar in the 2 groups. In both groups, adverse events related to venous thromboembolic prophylaxis were reported in 12 patients. The proportion of patients with minor and major fracture surgery was 74.3% and 25.7%, respectively. In patients undergoing minor fracture surgery receiving rivaroxaban (n=167) and the standard of care (n=140), no symptomatic thromboembolic events and no major bleeding events were reported. Outcomes of this study indicate that rivaroxaban might be an appropriate oral alternative for venous thromboembolic prophylaxis in routine medical care after fracture-related major and minor surgery. Reported results were comparable to those from other large-scale, noninterventional and randomized controlled studies. [Orthopedics. 2017; 40(2):109-116.].

Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial.

BACKGROUND: Articular cartilage injuries have poor repair capacity, leading to progressive joint damage, and cannot be restored predictably by either conventional treatments or advanced therapies based on implantation of articular chondrocytes. Compared with articular chondrocytes, chondrocytes derived from the nasal septum have superior and more reproducible capacity to generate hyaline-like cartilage tissues, with the plasticity to adapt to a joint environment. We aimed to assess whether engineered autologous nasal chondrocyte-based cartilage grafts allow safe and functional restoration of knee cartilage defects. METHODS: In a first-in-human trial, ten patients with symptomatic, post-traumatic, full-thickness cartilage lesions (2-6 cm2) on the femoral condyle or trochlea were treated at University Hospital Basel in Switzerland. Chondrocytes isolated from a 6 mm nasal septum biopsy specimen were expanded and cultured onto collagen membranes to engineer cartilage grafts (30 × 40 × 2 mm). The engineered tissues were implanted into the femoral defects via mini-arthrotomy and assessed up to 24 months after surgery. Primary outcomes were feasibility and safety of the procedure. Secondary outcomes included self-assessed clinical scores and MRI-based estimation of morphological and compositional quality of the repair tissue. This study is registered with ClinicalTrials.gov, number NCT01605201. The study is ongoing, with an approved extension to 25 patients. FINDINGS: For every patient, it was feasible to manufacture cartilaginous grafts with nasal chondrocytes embedded in an extracellular matrix rich in glycosaminoglycan and type II collagen. Engineered tissues were stable through handling with forceps and could be secured in the injured joints. No adverse reactions were recorded and self-assessed clinical scores for pain, knee function, and quality of life were improved significantly from before surgery to 24 months after surgery. Radiological assessments indicated variable degrees of defect filling and development of repair tissue approaching the composition of native cartilage. INTERPRETATION: Hyaline-like cartilage tissues, engineered from autologous nasal chondrocytes, can be used clinically for repair of articular cartilage defects in the knee. Future studies are warranted to assess efficacy in large controlled trials and to investigate an extension of indications to early degenerative states or to other joints. FUNDING: Deutsche Arthrose-Hilfe.

Regenerative Potential of Tissue-Engineered Nasal Chondrocytes in Goat Articular Cartilage Defects.

Nasal chondrocytes (NC) were previously demonstrated to remain viable and to participate in the repair of articular cartilage defects in goats. Here, we investigated critical features of tissue-engineered grafts generated by NC in this large animal model, namely cell retention at the implantation site, architecture and integration with adjacent tissues, and effects on subchondral bone changes. In this study, isolated autologous goat NC (gNC) and goat articular chondrocytes (gAC, as control) were expanded, green fluorescent protein-labelled and seeded on a type I/III collagen membrane. After chondrogenic differentiation, tissue-engineered grafts were implanted into chondral defects (6 mm in diameter) in the stifle joint for 3 or 6 months. At the time of explantation, surrounding tissues showed no or very low (only in the infrapatellar fat pad <0.32%) migration of the grafted cells. In repair tissue, gNC formed typical structures of articular cartilage, such as flattened cells at the surface and column-like clusters in the middle layers. Semi-quantitative histological evaluation revealed efficient integration of the grafted tissues with the adjacent native cartilage and underlying subchondral bone. A significantly increased subchondral bone area, as a sign for the onset of osteoarthritis, was observed following treatment of cartilage defects with gAC-, but not with gNC-grafts. Our results reinforce the use of NC-based engineered tissue for articular cartilage repair and preliminarily indicate their potential for the treatment of early osteoarthritic defects.