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Introduction: Within the last few decades, focused high-energy extracorporeal shockwave therapy (ESWT) has proven to be an effective alternative to standard of care revision surgery in delayed healing fractures or manifest non-unions in various anatomical regions., Materials and Methods: A retrospective multi-variant analysis of an open prospective, single-armed clinical study was conducted. Patients receiving focused high-energy ESWT for a delayed healing or an apparent non-union of a humeral fracture between January 1999 and December 2015 at a single trauma center were included in the study. Bony healing was defined as cortical continuity in three of four cortices and pain-free force loading and evaluated using CT scans and clinical examination at three- and six-month follow-ups after ESWT., Results: A total of 236 patients were included. N = 93 (43.8%) showed bony consolidation three months after ESWT and n = 105 (52.5%) after six months. Sub-group analysis showed significantly better healing for the proximal metaphyseal humerus (66.7% after six months, n = 42) compared to the diaphyseal region (48.1%, n = 133) and distal metaphyseal humerus (48.1%, n = 25). Regression analysis indicated significantly increased healing rates for patients of younger ages (p = 0.001) and a fracture diastasis of less than 5 mm (p = 0.002)., Conclusion: The findings of this study indicate that ESWT can be considered as a treatment option for a well-selected patient population despite the lower healing rates compared to other anatomical regions., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

A delay or failure to heal is the most common possible complication in clavicle fractures, especially in cases primarily treated conservatively. As the current standard therapy, surgical revision achieves good healing results, but is associated with potential surgery-related complications. Shockwave therapy as a non-invasive therapy shows similar reasonable consolidation rates in the non-union of different localizations, but avoids complications. Compromised clavicle fractures in the middle and lateral third treated with focused high-energy shockwave therapy were compared with those treated with surgical revision (ORIF). In addition, a three-dimensional computer simulation for evaluating the pressure distribution during shockwave application accompanied the clinical study. A comparable healing rate in bony consolidation was achieved in both groups. Significantly fewer complications, however, occurred in the shockwave group. The simulations showed safe application in this instance, particularly in avoiding lung tissue affection. When applied correctly, shockwaves represent a safe and promising therapy option for compromised clavicle fractures in the middle and lateral third.

Aim: To summarize developmental delay among infants and toddlers with sickle cell disease (SCD)., Method: This systematic review included studies that reported developmental outcomes of children with SCD between 0 months and 48 months of age and followed standards set forth by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines., Results: Ten studies were included, describing 596 unique developmental assessments. The rate of developmental delay ranged from 17.5% to 50% and increased with age. Cognition was the only domain included in all studies and the most frequently identified delay. One study reported that more severe SCD genotypes predicted worse development, while five studies reported no difference in rates of developmental delay across genotypes., Interpretation: These findings emphasize the need for standardized screening to identify children with SCD at risk of delay at a young age to facilitate appropriate referrals for therapeutic intervention. Frequent and comprehensive developmental screening is necessary among all SCD genotypes., (© 2021 Mac Keith Press.)

Due to its low invasive nature, arthroscopy nowadays represents the gold standard in the treatment of native joint empyema. This article gives a summary of the literature with expert recommendations, reviews and case reports on arthroscopic treatment of native joint empyema and the limitations. Most cases of native joint empyema can be successfully cleansed with arthroscopic treatment alone including lavage and débridement. In advanced stages of infection open arthrotomy is often needed for final infection cleansing. In postoperative infections with enclosed foreign material, such as after cruciate ligament reconstruction, the foreign material can in most cases be left in and successful infection eradication can be carried out with several arthroscopic lavages and débridement. In cases of higher grade infections with destruction of the joint, arthroscopic treatment alone is normally insufficient., (© 2021. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Extracorporeal shockwave therapy is a treatment modality, originally introduced into the clinic as lithotripsie, which has also been successfully used in the last two decades in the non-invasive treatment of delayed or non-healing fractures. Initially, the mechanism of action was attributed to microfracture-induced repair, but intensive basic research has now shown that the shockwave generates its effect in tissue via mechanotransduction. Numerous signal transduction pathways have already been demonstrated, which in their entirety trigger an endogenous regeneration process via cell proliferation, migration and differentiation. Clinically, these shockwave-conveyed biological signals support healing of acute, delayed and non-union fractures. The attainable outcome is comparable to surgery but avoiding an open approach with associated potential complications. These advantageous properties with a clearly positive cost-benefit ratio make shockwave therapy a first line treatment in delayed and non-union fractures., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Massive rotator cuff (RC) tears still present a clinically challenging problem, with reported rerupture rates in up to 94%. The study objective was to determine the impact of synthetic patch augmentation for massive RC tears., Methods: Between June 2012 and 2014, we performed 50 arthroscopic RC reconstructions augmented with a synthetic polyester patch. Pre- and postoperative imaging methods included arthrographic magnetic resonance imaging, arthrographic computed tomography, and ultrasound examination to determine tendon integrity or rerupture. Clinical outcome was evaluated using the Constant-Murley score and the subjective shoulder value. Mean clinical midterm and final follow-up was 22 months (9-35 months) and 52 months (25-74 months), respectively., Results: The mean Constant-Murley score increased significantly from 36.5 (±16.4 standard deviation [SD]) preoperatively to a midterm value of 81.2 (±9.6 SD; P < .0001) and further improved to a mean of 83.4 (±10.8 SD) at final follow-up. The mean subjective shoulder value increased from 40.3 (±24.3 SD) to 89.2 (±12.9 SD; P < .0001) at midterm and to 89.6 (±15.2 SD) at final follow-up. We observed 7 complete reruptures (14%). However, reruptures did not correlate with revision surgery, which was performed in 8 patients. The main reason for revision was frozen shoulder or arthrofibrosis with an intact reconstruction and patch, which was performed in 6 cases., Conclusions: The retear rate of 14% compared favorably with nonaugmented RC repairs in the literature. Therefore, we conclude that patch augmentation in massive RC tears is feasible to reduce retears and to improve clinical outcome., (Copyright © 2019 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

In a retrospective study the association of the production of extracellular DNA (eDNA) in biofilms of clinical staphylococcal isolates from 60 patients with prosthetic joint infection (PJI) and the clinical outcome were investigated. Data from a previous study on eDNA production determined in 24-hour biofilms of staphylococcal isolates (S taphylococcus aureus n=30, Staphylococcus epidermidis n=30) was correlated with the patients' clinical outcome after 3 and 12 months. Statistical analysis was performed using either the Spearman's rank correlations test or the t-test. eDNA production of S. epidermidis in 24-hour biofilms correlated with the patients' outcome 'not cured' after 12 months. For S. aureus no such correlation was detected. Thus, eDNA may be a virulence factor of S. epidermidis. Quantification of eDNA production as a surrogate marker for biofilm formation might be a potential predictive marker for the management of PJI.

Tibial non-unions are common cause of demanding revision surgeries and are associated with a significant impact on patients' quality of life and health care costs. Extracorporeal shockwave therapy (ESWT) has been shown to improve osseous healing in vitro and in vivo. The main objective of present study was to evaluate the efficacy of ESWT in healing of tibial non-unions unresponsive to previous surgical and non-surgical measures. A retrospective multivariant analysis of a prospective open, single-centre, clinical trial of tibia non-union was conducted. 56 patients with 58 eligible fractures who met the FDA criteria were included. All patients received 3000-4000 impulses of electrohydraulic shockwaves at an energy flux density of 0.4mJ/mm(2) (-6dB). On average patients underwent 1.9 times (±1.3SD) surgical interventions prior to ESWT displaying the rather negatively selected cohort and its limited therapy responsiveness. In 88.5% of patients receiving ESWT complete bone healing was observed after six months irrespective of underlying pathology. The multivariant analysis showed that time of application is important for therapy success. Patients achieving healing received ESWT earlier: mean number of days between last surgical intervention and ESWT (healed - 355.1 days±167.4SD vs. not healed - 836.7 days±383.0SD; p<0.0001). ESWT proved to be a safe, effective and non-invasive treatment modality in tibial non-unions recalcitrant to standard therapies. The procedure is well tolerated, time-saving, lacking side effects, with potential to significantly decrease health care costs. Thus, in our view, ESWT should be considered the treatment of first choice in established tibial non-unions., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Sustained, local, low dose growth factor stimulus of target tissues/cells is believed to be of imminent importance in tissue regeneration and engineering. Recently, a technology was developed to bind growth factors to a fibrin matrix using the transglutaminase (TG) activity of factor XIIIa, thus allowing prolonged release through enzymatic cleavage. In this study we aimed to determine whether TG-PDGF.AB in fibrin could improve tissue regeneration in a standard ischemic flap model. In vitro determination of binding and release kinetics of TG-PDGF.AB allowed proof of concept of the developed binding technology. A single spray application of TG-PDGF.AB in fibrin matrix at a concentration of 10 and 100ng/ml significantly reduced ischemia-induced flap tissue necrosis in vivo on day 7 after ischemic impact compared to controls. TG-PDGF.AB at a concentration of 100ng/ml fibrin induced distinct angiogenesis as reflected by significantly improved tissue perfusion assessed by laser Doppler imaging as well as enhanced von Willebrand factor (vWF) protein expression determined by immunohistochemical means. In addition, significantly more mature microvessels were observed with 100ng/ml TG-PDGF.AB in fibrin compared to control and vehicle groups as evidenced by an improved smooth muscle actin (sma)/vWF protein ratio. In conclusion, PDGF.AB in a conjugated fibrin matrix effectively reduced ischemia-induced tissue necrosis, increased tissue perfusion and induced the growth of a mature and functional neovasculature. The sealing properties of the fibrin matrix in conjunction with the prolonged growth factor stimulus enabled by the TG-hook binding technology may present an innovative and suitable tool in tissue regeneration., Statement of Significance: In our experimental study we elucidated recombinant platelet derived growth factor (PDGF) as a potential candidate in inducing angiogenesis. To avoid preterm growth factor degradation in vivo PDGF.AB was covalently linked to a fibrin scaffold using a bi-domain functionalized peptide (FXIII substrate site and plasmin cleavage site). This allowed PDGF binding to fibrin during spray application to the donor site and subsequent prolonged release via endogenous plasmin. This resulted in a mature vascular network thus enhancing tissue perfusion and consequently improved clinical outcome. With our present work we could certainly provide researchers and clinicians with an innovative versatile and reproducible technology not only to induce functional vascularity but also to improve attempts in tissue engineering in general by e.g. using different growth factors. Hence, we believe that this approach studied in the present work may provide a valuable input in an effort to drive the aim forward bringing experimental work in tissue engineering to clinic by using a clinically well characterized and used fibrin scaffold in combination with a human recombinant growth factor (fibrin scaffold linked with the specific binding technology)., (Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Fracture non-unions are still a challenging problem in orthopedics. The treatment of non-unions remains highly individualized, complex, and demanding. In most countries the surgical approach with debridement of the non-union gap, anatomical reduction and appropriate osteosynthesis along with autologous bone grafting is considered as the standard of care. One of the very first non-urologic applications of extracorporeal shockwave treatment (ESWT) concerned non-healing fractures. Since the early 1990ties the knowledge of the working mechanism has increased enormously. The purpose of this review article is to demonstrate by peer-reviewed literature in conjunction with our own experiences that ESWT can be an efficient, non-invasive, almost complication-free and cost effective alternative to surgical treatment of non-healing fractures., (Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.)

Background: Mesenchymal chondrosarcoma (MCS) is a distinct, very rare sarcoma with little evidence supporting treatment recommendations., Patients and Methods: Specialist centres collaborated to report prognostic factors and outcome for 113 patients., Results: Median age was 30 years (range: 11-80), male/female ratio 1.1. Primary sites were extremities (40%), trunk (47%) and head and neck (13%), 41 arising primarily in soft tissue. Seventeen patients had metastases at diagnosis. Mean follow-up was 14.9 years (range: 1-34), median overall survival (OS) 17 years (95% confidence interval (CI): 10.3-28.6). Ninety-five of 96 patients with localised disease underwent surgery, 54 additionally received combination chemotherapy. Sixty-five of 95 patients are alive and 45 progression-free (5 local recurrence, 34 distant metastases, 11 combined). Median progression-free survival (PFS) and OS were 7 (95% CI: 3.03-10.96) and 20 (95% CI: 12.63-27.36) years respectively. Chemotherapy administration in patients with localised disease was associated with reduced risk of recurrence (P=0.046; hazard ratio (HR)=0.482 95% CI: 0.213-0.996) and death (P=0.004; HR=0.445 95% CI: 0.256-0.774). Clear resection margins predicted less frequent local recurrence (2% versus 27%; P=0.002). Primary site and origin did not influence survival. The absence of metastases at diagnosis was associated with a significantly better outcome (P<0.0001). Data on radiotherapy indications, dose and fractionation were insufficiently complete, to allow comment of its impact on outcomes. Median OS for patients with metastases at presentation was 3 years (95% CI: 0-4.25)., Conclusions: Prognosis in MCS varies considerably. Metastatic disease at diagnosis has the strongest impact on survival. Complete resection and adjuvant chemotherapy should be considered as standard of care for localised disease., (Copyright © 2014 Elsevier Ltd. All rights reserved.)