Controversies in regenerative medicine: should knee joint osteoarthritis be treated with mesenchymal stromal cells?

Knee joint osteoarthritis is a complex immunological and degenerative disease. Current treatment strategies fail to alter its progression. Mesenchymal stromal cell (MSC) therapy for osteoarthritis has been object of research for more than 30 years. The aim of MSC therapy is intended to be holistic, with regeneration of all affected knee joint structures. The paracrine effect of the MSC secretome has been shown to be central for the regenerative capacity of MSCs. Activation of local knee-joint-specific MSCs leads to an immunomodulatory, anti-catabolic, anti-apoptotic and chondrogenic stimulus. Preclinical models have demonstrated the symptom- and disease-modifying effects of MSC therapy. At the bedside, there is evidence that autologous and allogeneic MSC therapy shows significant improvement in symptom-modifying and functional outcome. Despite this, a variety of contradictory clinical outcomes are available in the literature. The effectiveness of MSC therapy is still unclear, although there have been promising results. Regarding the diversity of cell sources, isolation, culture protocols and other factors, a comparison of different studies is difficult. Clinical translation of disease-modifying effects has not yet been shown. This narrative review presents a controversial overview of the current preclinical and clinical studies on MSC therapy in knee joint osteoarthritis.

ARoCuS Web application promotes standardized treatment and documentation of rotator cuff tears.

PURPOSE: To program a Web application for simplified calculation of the Advanced Rotator Cuff tear Score (ARoCuS), which is a 5-part, 18-item treatment-oriented intraoperative scoring system for intraoperative evaluation of rotator cuff tears. METHODS: ARoCuS characteristics (torn tendon, tear size, tissue quality and tear pattern) were assessed intraoperatively on 40 consecutive patients with rotator cuff tears for calculation of defect category ΔV. Video recordings were used to re-calculate the ARoCuS after surgery and to assess inter-observer reliability. RESULTS: The Web application "ARoCuS App" was built using Angular and transformed to a native iOS application. The intraoperative use of the app proved to be simple and intuitive. There were inter-/intra-observer differences neither in ARoCuS defect categories ΔV nor in ARoCuS characteristics (p > 0.05). CONCLUSION: The ARoCuS app is a supportive tool for integration of standardized treatment procedures and documentation of rotator cuff tears in clinical routine.

A survey on surgeon practice shows lack of consensus on the management of primary shoulder stiffness.

Shoulder stiffness is a condition of painful restriction in active and passive glenohumeral range of motion, which can arise spontaneously or as consequence of a known cause. Numerous therapeutic approaches are available; however, no consensus has been reached on the best algorithm for successful treatment. The aim of this study was to investigate local practice patterns regarding management of primary shoulder stiffness. Randomized controlled trials reporting results of shoulder stiffness treatment were collected and analyzed prior to study begin. Controversial elements in the treatment of primary shoulder stiffness were identified and a survey was created and administrated to clinicians participating at an annual national congress dedicated to shoulder pathologies and their treatment. 55 completed questionnaires were collected. Physical therapy was recommended by 98% of the interviewed. The use of oral corticosteroids was considered by 58% and injections of corticosteroids by 60%. Injective therapy with local anaesthetics was considered by 56% of the clinicians and acupuncture by 36%. 38% of the interviewed did never treat shoulder stiffness surgically. Various strategies to manage shoulder stiffness have been proposed and high-level evidence has been published. Numerous controversial points and a substantial lack of consensus emerged both from literature reviews and from this survey. The treatment of shoulder stiffness should be tailored to the patient's clinical situation and the stage of its pathology, aiming primarily at identifying risk factors for recurrence, reducing pain, restoring range of motion and function and shortening the duration of symptoms.

Microfracture combined with anterior cruciate ligament reconstruction compared to isolated microfractures for osteochondral lesions.

There is limited evidence whether increased growth-factor and stem-cell influx during bone tunnel drilling for ACL-reconstruction enhances clinical results of microfracture treatment of small cartilage defects. The goal of this study was to compare clinical and radiological results in patients treated with microfracture alone and patients treated with microfracture plus ACL-reconstruction. A total of 67 patients that were either treated with microfracture alone (primary stable knees, n= 40) or microfracture plus ACL-reconstruction (ACL deficient knees, n= 27) were included and prospectively evaluated. Subjects were preoperatively assessed radiologically using the MR-based AMADEUS-score (Area Measurement and Depth & Underlying Structures) and clinically using the Lysholm-score before the intervention. At minimum 24-month follow-up, the regenerate tissue was assessed by the MR-based MOCART-score (Magnetic resonance observation of cartilage repair tissue) and by use of the Lysholm-Tegner-score for clinical evaluation. Preoperatively both groups had similar AMADEUS-scores. The Lysholm-score was significantly higher in the microfracture group (p < 0.001). In the postoperative assessment there was a significant difference (p = 0.04) in the MOCART-score in favor of the microfracture plus ACL-reconstruction group. The Lysholm-score significantly improved (p <0.001) in the microfracture plus ACL-reconstruction group and was significantly higher than in the microfracture group (p = 0.004). Conclusion: A combination of microfracture and ACL-reconstruction leads to comparable functional results, yet superior MOCART-scores as compared to microfracture alone. ACL reconstruction enhances biological healing responses in microfracture treated cartilage and thus improves clinical outcomes by additional bone marrow influx from bone tunnels.

Mid-term results after revision total hip arthroplasty with custom-made acetabular implants in patients with Paprosky III acetabular bone loss.

INTRODUCTION: Severe acetabular bone loss, both with or without pelvic discontinuity, remains a challenge in revision total hip arthroplasty (RTHA). The goal of our study was to evaluate the mid-term results for consecutive patients with Paprosky III acetabular bone loss with or without pelvic discontinuity who needed RTHA with custom-made acetabular implants and to compare the results to those of other studies. MATERIALS AND METHODS: Sixty-eight (68) patients with severe acetabular bone loss (Paprosky Type IIIa and IIIb), who required RTHA, were included in our study. All prostheses were constructed on the basis of thin-layer computed tomography (CT) scans of the pelvis. The visual analogue scale (VAS), Harrison hip score (HHS), and clinical and radiographic follow-up assessments were used to evaluate the outcome. RESULTS: The average follow-up time was 43 months (range 1-120 months). Implant survival at last follow-up was 75% (51 of 68). Kaplan-Meier survival analysis, with explantation as the endpoint, revealed survival rates of 82.7% (3 years) and 77% (5 years). Patients with revision of the acetabular component only had a significant higher survival rate (p 0.012). Overall revision rate was 36.7%. Reinfection rate was 34.4%. Complications included 15 (22%) periprosthetic joint infections (PJI), 7 dislocations (10.2%), and 2 aseptic loosenings (2.9%). Mean VAS at last follow-up was 1.45 compared to 3.2 preoperatively, while mean HHS improved from 21.1 points preoperatively to 61 at last follow-up. The change in both scores was thus significant (p < 0.001). CONCLUSION: Defect reconstruction with custom-made modular acetabular implants can be a good, nevertheless expensive, treatment option with clinically and radiologically satisfying results in comparison to recent studies in the literature. Nevertheless, high postoperative complication rates, especially in terms of PJI, remain a challenge.

Advanced Rotator Cuff Tear Score (ARoCuS): a multi-scaled tool for the classification and description of rotator cuff tears.

BACKGROUND: To introduce a (semi-)quantitative surgical score for the classification of rotator cuff tears. MATERIAL AND METHODS: A total of 146 consecutive patients underwent rotator cuff repair and were assessed using the previously defined Advanced Rotator Cuff Tear Score (ARoCuS) criteria: muscle tendon, size, tissue quality, pattern as well as mobilization of the tear. The data set was split into a training (125 patients) and a testing set (21 patients). The training data set fitted a nonlinear predictive model of the tear score based on the ARoCuS criteria, while the testing data served as control. Based on the scoring results, rotator cuff tears were assigned to one of four categories (ΔV I-IV) and received a stage-adapted treatment. For statistical analysis, mean values ± standard deviation, interclass correlation coefficients (ICC) and kappa values were calculated. RESULTS: Overall, 32 patients were classified as ΔV I, 68 as ΔV II and 37 as ΔV III. Nine patients showed ΔV IV tears. Patients of all ΔV groups improved significantly their Constant scores (p < 0.001) and profited from significant pain reduction after surgery (p < 0.001). To date, ten patients have undergone revision surgery with five of them primarily classified as ΔV IV. Kappa values for the interobserver reliability ranged between 0.69 and 0.95. ICC scores for the ΔV category were 0.95 for interobserver reliability. CONCLUSIONS: The ARoCuS facilitates intra-operative decision-making and enables surgeons and researches to document rotator cuff tears in a standardized and reproducible manner.