Defects in B-lymphopoiesis and B-cell maturation underlie prolonged B-cell depletion in ANCA-associated vasculitis.

OBJECTIVES: B-cell depletion time after rituximab (RTX) treatment is prolonged in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) compared with other autoimmune diseases. We investigated central and peripheral B-cell development to identify the causes for the defect in B-cell reconstitution after RTX therapy. METHODS: We recruited 91 patients with AAV and performed deep phenotyping of the peripheral and bone marrow B-cell compartment by spectral flow and mass cytometry. B-cell development was studied by in vitro modelling and the role of BAFF receptor by quantitative PCR, western blot analysis and in vitro assays. RESULTS: Treatment-naïve patients with AAV showed low transitional B-cell numbers, suggesting impaired B-lymphopoiesis. We analysed bone marrow of treatment-naïve and RTX-treated patients with AAV and found reduced B-lymphoid precursors. In vitro modelling of B-lymphopoiesis from AAV haematopoietic stem cells showed intact, but slower and reduced immature B-cell development. In a subgroup of patients, after RTX treatment, the presence of transitional B cells did not translate in replenishment of naïve B cells, suggesting an impairment in peripheral B-cell maturation. We found low BAFF-receptor expression on B cells of RTX-treated patients with AAV, resulting in reduced survival in response to BAFF in vitro. CONCLUSIONS: Prolonged depletion of B cells in patients with AAV after RTX therapy indicates a B-cell defect that is unmasked by RTX treatment. Our data indicate that impaired bone marrow B-lymphopoiesis results in a delayed recovery of peripheral B cells that may be further aggravated by a survival defect of B cells. Our findings contribute to the understanding of AAV pathogenesis and may have clinical implications regarding RTX retreatment schedules and immunomonitoring after RTX therapy.

IL-7 receptor signaling drives human B-cell progenitor differentiation and expansion.

Although absence of interleukin-7 (IL-7) signaling completely abrogates T and B lymphopoiesis in mice, patients with severe combined immunodeficiency caused by mutations in the IL-7 receptor α chain (IL-7Rα) still generate peripheral blood B cells. Consequently, human B lymphopoiesis has been thought to be independent of IL-7 signaling. Using flow cytometric analysis and single-cell RNA sequencing of bone marrow samples from healthy controls and patients who are IL-7Rα deficient, in combination with in vitro modeling of human B-cell differentiation, we demonstrate that IL-7R signaling plays a crucial role in human B lymphopoiesis. IL-7 drives proliferation and expansion of early B-cell progenitors but not of pre-BII large cells and has a limited role in the prevention of cell death. Furthermore, IL-7 guides cell fate decisions by enhancing the expression of BACH2, EBF1, and PAX5, which jointly orchestrate the specification and commitment of early B-cell progenitors. In line with this observation, early B-cell progenitors of patients with IL-7Rα deficiency still expressed myeloid-specific genes. Collectively, our results unveil a previously unknown role for IL-7 signaling in promoting the B-lymphoid fate and expanding early human B-cell progenitors while defining important differences between mice and humans. Our results have implications for hematopoietic stem cell transplantation strategies in patients with T- B+ severe combined immunodeficiency and provide insights into the role of IL-7R signaling in leukemogenesis.

10-year follow-up of the Columbus knee prostheses system in a prospective multicenter study.

INTRODUCTION: As endpoint of a prospective multicenter 10-year documentation using the Columbus system, this evaluation carried out results of clinical scores (Knee Society Score and Oxford Knee Score), an evaluation of radiological imaging, survival rates and a collection of complication statistics. MATERIALS AND METHODS: There was a multicenter prospective recruitment of consecutive patients with the indication for total knee replacement (TKR). Preoperatively and 10 years after implantation, clinical scores, range of motion and radiological imaging was performed. During this period, a detailed documentation of complications was made. RESULTS: A total of 210 patients were recruited in 5 centers. 140 patients were available for endpoint examination 10 years after surgery. A survival rate of 96.6% (CI 95%) for the implanted Columbus prostheses after 10 years was demonstrated. Cumulative KSS showed an improvement of 75.3 (± 38.1) points and was highly significant (p < 0.0001, t test). The average functional improvement in the Oxford score was 20.6 (± 9.5) points and was also highly significant (p < 0.0001). The ROM improved from 106.5° (± 20.5) preoperatively to 116.0° (± 11.5) (p < 0.0001, t test). There were no implant-related complications as well as no new complication documented between 5- and 10-year follow-up. CONCLUSIONS: The endpoint analysis after an observation period of 10 years provided good clinical and radiographic results. In particular, an excellent survival rate of 96.6% after 10 years was demonstrated. The data published in this study are the first to be available in a prospective multicenter study on this system, which leads to a high level of clinical significance.

Inhibition of the anti-apoptotic protein MCL-1 severely suppresses human hematopoiesis

BH3-mimetics inhibiting anti-apoptotic BCL-2 proteins represent a novel and promising class of antitumor drugs. While the BCL-2 inhibitor venetoclax is already FDA-approved, BCL-XL and MCL-1 inhibitors are currently in early clinical trials. To predict side effects of therapeutic MCL-1 inhibition on the human hematopoietic system, we used RNAi and the small molecule inhibitor S63845 on cord blood-derived CD34+ cells. Both approaches resulted in almost complete depletion of human hematopoietic stem and progenitor cells. As a consequence, maturation into the different hematopoietic lineages was severely restricted and CD34+ cells expressing MCL-1 shRNA showed a very limited engraftment potential upon xenotransplantation. In contrast, mature blood cells survived normally in the absence of MCL-1. Combined inhibition of MCL-1 and BCL-XL resulted in synergistic effects with relevant loss of colony-forming HSPCs already at inhibitor concentrations of 0.1 µM each, indicating "synthetic lethality" of the two BH3-mimetics in the hematopoietic system.

Nonpermissive bone marrow environment impairs early B-cell development in common variable immunodeficiency.

Common variable immunodeficiency (CVID) is a disease characterized by increased susceptibility to infections, hypogammaglobulinemia, and immune dysregulation. Although CVID is thought to be a disorder of the peripheral B-cell compartment, in 25% of patients, early B-cell development in the bone marrow is impaired. Because poor B-cell reconstitution after hematopoietic stem cell transplantation has been observed, we hypothesized that in some patients the bone marrow environment is not permissive to B-cell development. Studying the differentiation dynamics of bone marrow-derived CD34+ cells into immature B cells in vitro allowed us to distinguish patients with B-cell intrinsic defects and patients with a nonpermissive bone marrow environment. In the former, immature B cells did not develop and in the latter CD34+ cells differentiated into immature cells in vitro, but less efficiently in vivo. In a further group of patients, the uncommitted precursors were unable to support the constant development of B cells in vitro, indicating a possible low frequency or exhaustion of the precursor population. Hematopoietic stem cell transplantation would result in normal B-cell repopulation in case of intrinsic B-cell defect, but in defective B-cell repopulation in a nonpermissive environment. Our study points to the importance of the bone marrow niche in the pathogenesis of CVID.

Biomechanical dynamic comparison of biodegradable pins and titanium screws for operative stabilization of displaced radial head fractures.

For radial head osteosynthesis, biodegradable implants are gaining in importance to minimize cartilage destruction and implant impingement and to supersede implant removal. Since loss of reduction and pseudarthrosis remain challenging complications, new implants should at least provide comparable biomechanical properties as commonly used metal implants. The objective of this study was to compare the treatment by polylactide pins to titanium screws and to quantify the produced cartilage defects. Eight pairs of human cadaver radii with a standardized Mason type II fracture were stabilized either by two 2.0-mm polylactide pins or titanium screws. The produced cartilage defects were quantified using an image analyzing software. Quasi-static loading was performed axially and transversally for 10 cycles each between 10 and 50 N. Afterward, implant loosening was tested by axial loading up to 10,000 cycles, followed by load to failure testing. Polylactide pins showed less construct stiffness under axial (p = 0.017) and transversal (p = 0.012) loading, and one polylactide pins construct failed after two cycles of transversal loading. At axial loading, a high correlation between bone mineral density and construct stiffness was observed among polylactide pins (R = 0.667; p = 0.071), which was not seen among titanium screws (R = 0.262; p = 0.531). No difference in implant loosening was recorded after 10,000 cycles (p = 0.237); however, one polylactide pins construct failed after 30 cycles and failure loads were higher for titanium screws (p=0.017). Polylactide pin produced smaller cartilage defects (p=0.012). In conclusion, simple radial head fractures treated by polylactide pins show less biomechanical stability than treated by titanium screws, particularly in osteoporotic bone which might lead to secondary loss of reduction. Due to smaller cartilage defects and equal properties under continuous loading, polylactide pins might represent a gentle alternative in patients with good bone quality making subsequent implant removal redundant.

Identifying Disparities in the Management of Hip Fractures Within Europe: A Comparison of 3 Health-Care Systems.

INTRODUCTION: This study investigates the management of hip fractures in a German maximum care hospital and compares these data to evidence-based standard and practice in 180 hospitals participating in the UK National Hip Fracture Database (NHFD) and 16 hospitals participating in the Irish Hip Fracture Database (IHFD). This is the first study directly comparing the management of hip fractures between 3 separate health-care systems within Europe. METHODS: Electronic medical data were collected retrospectively describing the care pathway of elderly patients with a hip fracture admitted to a large trauma unit in the south of Germany "University Hospital Freiburg" (UHF). The audit evaluated demographics, postoperative outcome, and the adherence to the 6 "Blue Book" standards of care. These data were directly compared with the data from the UK NHFD and the IHFD acquired from 180 and 16 hospitals, respectively. RESULTS: At 36 hours, 95.8% of patients had received surgery in UHF, compared to 71.5% in the NHFD and 58% of patients in the IHFD. The rate of in-hospital mortality was 4.7% compared to 7.1% in the NHFD and 5% in the IHFD. The mean average acute length of stay was 13.4 days compared to 16.4 days in the NHFD and 20 days in the IHFD. Reoperation rates are 3.3% compared to 1% in the NHFD and 1.1% in the IHFD; 50.5% of patients were discharged on bone protection medication, compared to 47% in the IHFD and 79.3% in the UK NHFD. DISCUSSION: Despite uniformly acknowledged evidence-based treatment guidelines, the management of hip fractures remains heterogeneous within Europe. CONCLUSION: These data show that different areas of the hip fracture care pathway in Germany, England, and Ireland, respectively, show room for improvement in light of the growing socioeconomic burden these countries are expected to face.

Biomechanical in vitro evaluation of a ready-to-use calcium phosphate cement implanted to augment intramedullary nail fixation of a three-part humeral head fracture model.

The aim of this study was the dynamic biomechanical evaluation of a ready-to-use oil-based calcium phosphate cement paste implanted to augment intramedullary nail fixation of a three-part humeral head fracture model. Fractures in the osteoporotic bone are often fractures of the proximal humerus. Secondary fracture displacements due to cut-out in osteoporotic bone have been observed in up to 13% of cases. Procedures have been developed to augment fracture fixation with polymethylmethacrylate to increase stability, but there are still unsolved challenges relating to its material-specific properties. Calcium phosphate cement could be a biological alternative in the augmentation of osteoporotic fractures because of its more favourable material properties. Fracture fixation was performed on eight pairs of human cadaveric bones to stabilize a standardized three-part humeral head fracture model by implantation of the Targon® PH (Braun-Aesculap AG, Tuttlingen, Germany) intramedullary nail and insertion of three head screws and two bicortical shaft screws. The procedure was randomized, and one bone of each pair received calcium phosphate cement augmentation. Custom-made cannulated screws with an open lateral slot facilitated augmentation, making it possible to cement the threaded portion of the screw (1-mL calcium phosphate cement/screw). After the calcium phosphate cement had hardened, the humeri were subjected to dynamic axial loading. Load was progressively increased, monitored by ultrasound-based motion analysis, and total deformation was recorded. Load testing continued until implant failure. The augmented group withstood significantly more cycles before implant failure. The average initial stiffness showed a significant difference between the two study groups. Ultrasonic sensor technology was used to measure angular displacement during testing and a significant difference was found. Calcium phosphate cement offers a potential alternative to implant augmentation in the treatment of osteoporotic humeral head fractures. Future studies are required to confirm these observations clinically in vivo.

Histopathological effects of modern topical sealants on the liver surface after hepatectomy: an experimental swine study.

The present study aimed to determine the impact of different sealant materials on histopathological changes to the liver surface after liver resection. Thirty-six landrace pigs underwent left anatomical hemihepatectomy and were assigned to a histopathological control group (HPC, n = 9) with no bleeding control, a clinically simulated control group (CSC, n = 9) with no sealant but bipolar cauterization and oversewing of the liver surface, and two treatment groups (n = 9 each) with a collagen-based sealant (CBS) or a fibrinogen-based sealant (FBS) on resection surface. After postoperative day 6, tissue samples were histologically examined. There were no significant differences in preoperative parameters between the groups. Fibrin production was higher in sealant groups compared with the HPC and CSC groups (both p < 0.001). Hepatocellular regeneration in sealant groups was higher than in both control groups. A significantly higher regeneration was seen in the FBS group. Use of sealants increased the degree of fibrin exudation at the resection plane. Increased hepatocellular necrosis was seen in the CBS group compared with the FBS group. The posthepatectomy hepatocellular regeneration rate was higher in the FBS group compared with the CBS group. Randomized studies are needed to assess the impact of sealants on posthepatectomy liver regeneration in the clinical setting.

Rehabilitation before regenerative cartilage knee surgery: a new prehabilitation guideline based on the best available evidence.

INTRODUCTION: Focal cartilage defects are an increasingly relevant clinical problem especially in athletes. Cartilage regenerative surgery (CRS) including microfracture and autologous chondrocyte implantation (ACI) to treat such isolated cartilage defects in the knee joint has been well established in the last two decades. In contradiction to high-level evidence concerning the surgical technique, cell-related issues, and clinical results, the knowledge about the optimal rehabilitation process is still sparse although the importance of optimizing the rehabilitation process has recently led to new research focus in this field. The preoperative time frame may be used to start rehabilitation which may fasten the postoperative recovery and optimize clinical outcome ("Prehabilitation"-PREHAB). The aim of this article, therefore, was to review the available literature on prehabilitation concepts and to present a prehabilitation guideline for CRS patients based on the best evidence available. METHODS: A systemic literature research was conducted on rehabilitation for cartilage regenerative surgery as well as prehabilitation in knee joint procedures. From the available literature a prehabilitation concept was generated and tested in 10 ACI patients. RESULTS: As the literature search found no studies addressing prehabilitation in CRS patients, an evidence-based PREHAB program has been compiled based on the available evidence from (a) studies addressing postoperative rehabilitation in CRS patients and (b) PREHAB studies on other knee procedures including TKA. This presented prehabilitation guideline has been tested in > 50 CRS patients and was found to be feasible as all of the patients showed a good compliance and were able to perform the protocol as suggested. CONCLUSION: The presented PREHAB regimen may serve clinicians as a guideline for early rehabilitation of their CRS patients. Obviously, further research is mandatory to quantify its clinical effect and to demonstrate its cost-effectiveness and benefits in surgically treated patients.

[5-year follow-up of 210 Columbus knee prostheses : A prospective multicentre study]. / 5-Jahres-Follow-up von 210 Columbus-Knietotalendoprothesen : Eine prospektive multizentrische Studie.

INTRODUCTION: As part of 10-year documentation using the Columbus system, the interim evaluation was carried out 5 years after implantation with a collection of clinical scores, evaluation of radiological imaging and collection of statistics concerning complications. METHODS: There was a multicentre prospective recruitment of consecutive patients with the indication of implantation of a surface replacement prosthesis (Columbus CR, Deep Dish fixed inlay). Preoperatively, clinical scores were recorded (KSS and Oxford score). Five years postoperatively a new evaluation of clinical scores, the range of motion (ROM) and a radiological check-up including full leg imaging under load was performed. During this period, detailed complication documentation was made. RESULTS: A total of 210 patients were recruited in five centres. 187 patients were available for examination 5 years after surgery. Cumulative KSS increased from 87.5 (±26.6) preoperatively to 170 (±29.1) 5 years postoperatively. The cumulative KSS improvement was 81.5 (±35.2) points and was highly significant (p < 0.0001; t­test). The average functional improvement in the Oxford score between the preoperative and 5­year follow-up was 21.7 (±8.8) points and was also highly significant (p < 0.0001). The ROM improved from 106.3° (±20.2) preoperatively to 114.0° (±12.1) 5 years postoperatively (p < 0.0001; t test). Five years after implantation, the average mechanical leg axis was 178.0° (±2.1). There was no clinically apparent or native radiologic visible aseptic loosening of the femoral or tibial joint component. There were 33 complications, but no implant-related complications such as inlay dislocation, material fracture or aseptic loosening. In total, 6 revision surgeries were performed during the follow-up period, which corresponds to a survival rate of 97.1% (CI 95%) for the implanted Columbus knee in the present patient collective for 5 years. CONCLUSION: The interim analysis at 5 years of long-term observation of the Columbus system provided good clinical and radiographic results.

Evaluation of hemodynamic goal-directed therapy to reduce the incidence of bone cement implantation syndrome in patients undergoing cemented hip arthroplasty - a randomized parallel-arm trial.

BACKGROUND: The bone cement implantation syndrome (BCIS) is a frequent and potentially disastrous intraoperative complication in patients undergoing cemented hip arthroplasty. Several risk factors have been identified, however randomized controlled trials to reduce the incidence of BCIS are still pending. We hypothesized that goal-directed hemodynamic therapy guided by esophageal Doppler monitoring (EDM) may reduce the incidence of BCIS in a randomized, controlled parallel-arm trial. METHODS: After approval of the local ethics committee, 90 patients scheduled for cemented hip arthroplasty at the Medical Center - University of Freiburg were randomly assigned to either standard hemodynamic management or goal-directed therapy (GDT) guided by an esophageal Doppler monitoring-based algorithm. The primary endpoint was the incidence of overall BCIS including grade 1-3 after cementation of the femoral stem. Secondary endpoints included cardiac function, length of hospital stay and postoperative complications. RESULTS: Ninety patients were finally analyzed. With regards to the primary endpoint, the overall incidence of BCIS showed no difference between the GDT and control group. Compared to the control group, patients of the GDT group showed a higher cardiac index before and after bone cement implantation (2.7 vs. 2.2 [l●min- 1●m- 2]; 2.8 vs. 2.4 [l●min- 1●m- 2]; P = 0.003, P = 0.042), whereas intraoperative amount of fluids and mean arterial pressure did not differ. CONCLUSIONS: The implementation of a specific hemodynamic goal-directed therapy did not reduce the overall incidence of BCIS in patients undergoing cemented hip arthroplasty. TRIAL REGISTRATION: This randomized clinical two-arm parallel study was approved by the local Ethics Committee, Freiburg, Germany [EK 160/15, PI: U. Goebel] and registered in the German Clinical Trials Register ( DRKS No. 00008778 , 16th of June, 2015).

Hemostatic efficiency of modern topical sealants: Comparative evaluation after liver resection and splenic laceration in a swine model.

Parenchymal transection during hepatobiliary surgery can disrupt small vasculature or bile ducts, which could be managed difficultly. Sealants are helpful tools to achieve better hemostasis. The aim of this study is to analyze the hemostatic efficiency of four modern sealants in a porcine model. In this study, 40 landrace pigs were assigned equally to the control (without sealant) and four sealant groups. Standardized liver resection and splenic lesions were performed and left without using sealant (control) or treated with one of the following sealants: TachoSil® , Tissucol Duo® , Coseal® , and FloSeal® . We measured relative and absolute bleeding times (seconds) as well as total blood loss (g) in a maximum observation time of 300 s. Sealants could show a significantly improved hemostasis comparing to the control group. However, hemostasis was heterogeneous among the sealant groups (liver resection: 60%-100%, spleen injury: 70%-100%). The mean blood loss decreased significantly using sealants comparing to control group (liver resection: 6-120 fold, spleen injury: 2.5-36 fold). The hemostatic time in groups that achieved complete hemostasis was different in each sealant group (liver resection: 30-166 s, spleen injury: 60-180 s). We conclude that the hemostatic efficacy of modern sealants is impressive but heterogeneous in liver resection or splenic lesion. To maximize the effectiveness of these tools, the indication of each sealant should be carefully considered in individual settings by the surgeons. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1307-1316, 2018.

Analysis of the hemostatic potential of modern topical sealants on arterial and venous anastomoses: an experimental porcine study.

One of the widely accepted adjunctive agents in the variety of surgical modalities are sealants. Our study aim was to compare four commonly used modern sealants in a standardized experimental setting to assess their feasibility, and hemostatic efficacy in vascular anastomosis. Forty landrace pigs (weight: 24.7 ± 3.8 kg) were randomized into the control (n = 8) and four sealant groups; TachoSil® (n = 8), Tissucol Duo® (n = 8), Coseal® (n = 8), and FloSeal® (n = 8). After doing a portal vein end-to-end anastomosis as well as stitches of aortic incision, the sealants were applied on anastomotic site. The control group was left intact. In portal vein anastomosis, the sealants led to a complete hemostasis significantly better than control group. The mean of blood loss was also significantly reduced. In successful subgroups, there was a difference in the mean-time to reach complete hemostasis ranging from 15 s in Coseal® to 76 s in FloSeal® group (p < 0.05). In aortotomy experiments, except Tissucol Due®, which had insufficient hemostasis, other sealants led to a complete hemostasis. The mean blood loss was significantly reduced in sealants groups as well. The four sealants are effective in reducing the suture-hole bleeding in portal vein anastomosis. However, the hemostatic potential is heterogeneous among sealants. This means that "one-size-fits-all" approach is not appropriate for application of sealants in diversity of vascular surgery and it should be based on the type and the severity of injury and the structure of tissue. Comparison of hemostasis efficacy of four modern sealants (TachoSil®, Tissucol Duo®, Coseal®, and FloSeal®) in vascular anastomosis in porcine model. The figures below show the total blood loss (g) in the control and sealant groups after aortotomy (left) and portal vein anastomosis (right). The mean of blood loss decreased significantly by the usage of sealants in both experiment groups as compared to control group (*: p < 0.05; sealant groups vs. control group). 1. The right column shows the mean of blood loss (g) in all experiments in each group. 2. The middle column presents the subgroup with unsuccessful hemostasis at the end of observation time (Tmax = 20 sec. for aortotmy and 300 sec. for portal vein anastomosis). 3. The left column shows mean of total blood loss in subgroups with successful hemostasis during observation time (20 sec for aortotomy and 300 sec for portal vein).

[Prosthetic Joint Infection after Total Hip Arthroplasty: Results of an Online Questionnaire about Current Diagnostic and Therapeutic Procedures in 107 German Hospitals]. / Die infizierte Hüfttotalendoprothese: Eine Onlineumfrage zum aktuellen diagnostischen und therapeutischen Vorgehen in 107 deutschen Krankenhäusern.

Background Prosthetic hip joint infection is a common severe complication with a high socio-economic impact. The inconsistency of the available data and the absence of binding guidelines lead to a variety of diagnostic and therapeutic strategies. The aim of this study is to present the current diagnostic and therapeutic approach to treating infections after total hip arthroplasties in German hospitals, link it with current evidence, and evaluate the willingness of these hospitals to participate in prospective multicentre trials. Material and Methods An online questionnaire for digital processing was sent to hospitals performing joint replacement procedures. These institutions included district hospitals, private hospitals, non-university maximum care facilities, statutory accident insurance hospitals, and university hospitals. Results A total of 107 hospitals took part in the survey, corresponding to a response rate of 27.6%. These hospitals perform approximately 2,951 revisions of infected total hip arthroplasties per year. Two-stage revision arthroplasty is the preferred procedure after prosthetic hip infections. The algorithm proposed by Zimmerli et al. is widely recognised. There is a lack of uniformity in the key features for revision of prosthetic joint infections - long vs. short interval in case of two-stage revision, duration of intravenous and oral administration of antibiotics, cemented vs. cement-free implant procedures, and follow-up intervals after revision surgery. The willingness to participate in clinical trials is high. Conclusion The controversial data leads to multiple treatment approaches. The high willingness to participate in adequately funded clinical trials offers a potential for multicentre trials to be conducted. There is an urgent need for funding to make this research possible.

Quadriceps Strength in Patients With Isolated Cartilage Defects of the Knee: Results of Isokinetic Strength Measurements and Their Correlation With Clinical and Functional Results.

BACKGROUND: Recent studies have found a significant deficit of maximum quadriceps strength after autologous chondrocyte implantation (ACI) of the knee. However, it is unclear whether muscular strength deficits in patients with cartilage damage exist prior to operative treatment. PURPOSE: To isokinetically test maximum quadriceps muscle strength and quantify the impact of possible strength deficits on functional and clinical test results. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: To identify clinically relevant muscular strength deficits, 24 patients (5 females, 19 males; mean age, 34.5 years; body mass index, 25.9 kg/m2) with isolated cartilage defects (mean onset, 5.05 years; SD, 7.8 years) in the knee joint underwent isokinetic strength measurements. Maximal quadriceps strength was recorded in 3 different testing modes: pure concentric contraction (flexors and extensors alternating work; con1), concentric-eccentric (only the extensors work concentrically and eccentrically; con2), and eccentric contraction in the alternating mode (ecc). Results were compared for functional performance (single-leg hop test), pain scales (visual analog scale [VAS], numeric rating scale [NRS]), self-reported questionnaires (International Knee Documentation Committee [IKDC], Knee Injury and Osteoarthritis Outcome Scale [KOOS]), and defect size (cm2). RESULTS: Compared with the uninjured leg, significantly lower quadriceps strength was detected in the injured leg in all isokinetic working modes (con1 difference, 27.76 N·m [SD 17.47; P = .003]; con2 difference, 21.45 N·m [SD, 18.45; P =.025]; ecc difference, 29.48 N·m [SD, 21.51; P = .001]), with the largest deficits found for eccentric muscle performance. Moderate negative correlations were observed for the subjective pain scales NRS and VAS. The results of the IKDC and KOOS questionnaires showed low, nonsignificant correlations with findings in the isokinetic measurement. Moreover, defect sizes (mean, 3.13 cm2) were of no importance regarding the prediction of the strength deficit. The quadriceps strength deficit between the injured and the uninjured leg was best predicted by the results of the single-leg hop test. CONCLUSION: Patients with isolated cartilage defects of the knee joint have significant deficits in quadriceps muscle strength of the injured leg compared with the uninjured leg. The single-leg hop test may be used to predict quadriceps strength deficits. Future research should address whether preoperative strength training in patients with cartilage defects of the knee could be effective and should be taken into consideration in addition to surgical treatment.

Comparative analysis of locking plate versus hook plate osteosynthesis of Neer type IIB lateral clavicle fractures.

INTRODUCTION: Controversy exists on optimal operative treatment of vertically unstable Neer IIB lateral clavicle fractures. Aim of this study was to analyse and compare clinical and radiological results and complications of locking plate osteosynthesis (LPO) versus hook plate osteosynthesis (HPO) with acromioclavicular joint (ACJ) stabilization. The hypothesis was, that HPO would recreate coracoclavicular stability more effectively and potentially lead to a superior outcome. METHODS: This retrospective, observational cohort study included 32 patients (19 HPO, 13 LPO) with a mean age of 44.1 ± 14.2 years at surgery. The mean follow-up period was 54.2 months (range 25.2-111.4 months). Besides standard radiography, bilateral coracoclavicular distances were assessed by means of preoperative and follow-up stress radiographs after implant removal. Clinical outcome measures included the Constant score (CS), the Oxford shoulder score (OSS), the subjective shoulder value (SSV) and the Taft score (TS). RESULTS: Bone union occurred in all but one patient and proved to occur delayed in five patients (15.6%). Radiographical healing required a mean of 4.2 ± 4.0 months irrespective of the type of osteosynthesis. At follow-up, mean coracoclavicular distance was increased by 34% (±36) without significant differences between both groups. HPO patients obtained a significantly lower TS (HPO: 9.5 ± 1.5 points, LPO: 11.1 ± 1.3 points; p = 0.005). Other mean score values did not differ (CS: 90.1 ± 7.4 points, OSS: 43.2 ± 9.2 points, SSV: 91.1 ± 14.7%). Sixteen patients (50.0%) experienced complications. Overall prevalence of complications was significantly higher in the HPO group (p = 0.014). CONCLUSIONS: Both HPO and LPO were equally effective in relation to restoration of vertical stability, overall functional outcome and fracture consolidation in treatment of Neer IIB fractures. Contrary to our hypothesis, HPO was not associated with superior recreation of the coracoclavicular distance. Considerable drawbacks of HPO were an inferior ACJ-specific outcome (Taft-Score) and a higher overall complication rate. Level of evidence IV.

Upcoming Paralympic summer games in Rio: what did the German medical team learn from the London Games?

BACKGROUND: Musculoskeletal complaints are frequently diagnosed in Paralympic athletes. Despite the increased professionalism in Paralympic Sports, the documentation of injuries and other health complaints during high-level competition is sparse. With respect to the upcoming Paralympic Summer Games in Rio de Janeiro, the aim of this study was the analysis of all musculoskeletal complaints within the German Paralympic Athletes during the London 2012 Paralympic Games. METHODS: All musculoskeletal complaints (MSC) of the 150 German athletes seeking medical attention, hereby defined as "injury", were recorded during the in-competition period of the London Paralympics Games (22 days), regardless of their severity and consequences. Standardized documentation included the onset of symptoms, the medical diagnoses, the therapeutic measures taken as well as consecutive restrictions in training and competition. Incidence rates and localizations were analyzed by sports discipline. RESULTS: A total of 201 musculoskeletal complaints were recorded for 140 athletes (93.3%), corresponding to 1.4 musculoskeletal complaints per "injured" athlete. The incidence of musculoskeletal complaints in German athletes was 62.9±15.4/1000 athlete-days. High incidence rates (IR) were observed in wheelchair basketball (IR 72/1000 athlete-days, 1.6 injuries per athlete) and equestrian events (IR 72.7, 1.6). Musculoskeletal complaints were mainly located in the upper extremities (37.6%) and the spine (37.6%). The most frequent diagnoses were myalgia (N.=105, 52%). CONCLUSIONS: We noted a high rate of musculoskeletal complaints among German Paralympic athletes across sports and body parts, highlighting the need for prevention programs that focus on the upper extremities and spine.