An altered heparan sulfate structure in the articular cartilage protects against osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is a progressive degenerative disease of the articular cartilage caused by an unbalanced activity of proteases, cytokines and other secreted proteins. Since heparan sulfate (HS) determines the activity of many extracellular factors, we investigated its role in OA progression. METHODS: To analyze the role of the HS level, OA was induced by anterior cruciate ligament transection (ACLT) in transgenic mice carrying a loss-of-function allele of Ext1 in clones of chondrocytes (Col2-rtTA-Cre;Ext1e2fl/e2fl). To study the impact of the HS sulfation pattern, OA was surgically induced in mice with a heterozygous (Ndst1+/-) or chondrocyte-specific (Col2-Cre;Ndst1fl/fl) loss-of-function allele of the sulfotransferase Ndst1. OA progression was evaluated using the OARSI scoring system. To investigate expression and activity of cartilage degrading proteases, femoral head explants of Ndst1+/- mutants were analyzed by qRT-PCR, Western Blot and gelatin zymography. RESULTS: All investigated mouse strains showed reduced OA scores (Col2-rtTA-Cre;Ext1e2fl/e2fl: 0.83; 95% HDI 0.72-0.96; Ndst1+/-: 0.83, 95% HDI 0.74-0.9; Col2-Cre;Ndst1fl/fl: 0.87, 95% HDI 0.76-1). Using cartilage explant cultures of Ndst1 animals, we detected higher amounts of aggrecan degradation products in wildtype samples (NITEGE 4.24-fold, 95% HDI 1.05-18.55; VDIPEN 1.54-fold, 95% HDI 1.54-2.34). Accordingly, gelatin zymography revealed lower Mmp2 activity in mutant samples upon RA-treatment (0.77-fold, 95% HDI: 0.60-0.96). As expression of major proteases and their inhibitors was not altered, HS seems to regulate cartilage degeneration by affecting protease activity. CONCLUSION: A decreased HS content or a reduced sulfation level protect against OA progression by regulating protease activity rather than expression.

[Stimulation of fracture healing by growth factors and cell-based technologies]. / Stimulation der Frakturheilung durch Wachstumsfaktoren und zellbasierte Technologien.

Bone has the special capability to completely regenerate after trauma and to re-establish its original geometry and biomechanical stability corresponding to the pretrauma conditions. Nevertheless, in daily clinical practice impaired fracture healing and nonunions are regular complications as a result of inadequate mechanical stability and/or insufficient biological processes around the fracture region. Since the beginning of the millennium, intensive research on the physiological processes in bone healing as well as the production and clinical administration of growth factors have enabled the possibility to improve the local biological processes during fracture healing by osteoinduction. Although the initial clinical results, particularly of bone morphogenetic proteins, in fracture healing were promising, growth factors did not become established for unrestricted use in the clinical application. Currently, additional growth factors are being investigated with respect to the potential supportive and osteoinductive characteristics for enhancement of fracture healing and possible clinical applications. Furthermore, the development of cell-based technologies is another promising approach to positively stimulate fracture healing. In addition to the gold standard of autologous bone grafting, harvesting of mesenchymal stroma cells by aspiration has gained in importance in recent years. Allogeneic bone cell transplantation procedures and in particular gene therapy are promising new strategies for the treatment of disorders of fracture healing. This review gives an overview of present and future possibilities for modulation of fracture healing by growth factors and cell-based technologies.

[Safety culture in orthopedics and trauma surgery : Course concept: interpersonal competence by the German Society for Orthopaedics and Trauma (DGOU) and Lufthansa Aviation Training]. / Sicherheitskultur in Orthopädie und Unfallchirurgie : Kurskonzept: Interpersonal Competence by Deutsche Gesellschaft für Orthopädie und Unfallchirurgie (DGOU) and Lufthansa Aviation Training.

Patient safety has become a central and measurable key factor in the routine daily medical practice. The human factor plays a decisive role in safety culture and has moved into focus regarding the reduction of treatment errors and undesired critical incidents. Nonetheless, the systematic training in communication and interpersonal competences has so far only played a minor role. The German Society of Orthopaedics and Trauma (DGOU) in cooperation with the Lufthansa Aviation Training initiated a course system for interpersonal competence. Several studies confirmed the reduction of critical incidents and costs after implementation of a regular and targeted human factor training. The interpersonal competence should be an essential component of specialist training within the framework of a 3­column model.

[Interpersonal competence in orthopedics and traumatology : Why technical and procedural skills alone are not sufficient]. / Interpersonelle Kompetenz in Orthopädie und Unfallchirurgie : Warum technische und prozedurale Fähigkeiten alleine nicht ausreichen.

Patient safety has increasingly gained significance as criterion which clinics and doctors will be measured against in terms of ethics and finances. The "human factor" moved into focus regarding the question of how to reduce treatment errors in clinical daily routine. Nevertheless, systematic mediation of interpersonal competences only plays a minor role in the catalogue of requirements for medical specialization and professional training. This is the case not only in orthopedics and traumatology, but in other medical fields as well. At the insistence of DGOU and in cooperation with Lufthansa Flight Training, a training model was initiated, comparable to training models used in aviation. In aviation, apart from the training of procedural and technical abilities, regular soft skills training has become standard in the training of all Lufthansa staff. Several studies confirm that by improving communication, interaction, and teamwork skills not only a reduction of intolerable incidents is observed, but also a positive economic effect. Interpersonal competences should be firmly anchored in orthopedics and traumatology and thus be implemented as third post in specialist training.

[The Summer School of the German Society for Orthopaedics and Traumatology - A Success Story]. / Die Summer School der Deutschen Gesellschaft für Orthopädie und Unfallchirurgie ­ eine Erfolgsgeschichte.

Background: It has been known for several years that orthopaedic and trauma clinics suffer from a shortage of young people, due to the substantial loss in attractiveness. The Youth Forum OU has been addressing this problem for many years, by initiating many projects such as the Summer School to counteract this trend. The purpose of this research is to evaluate the success of Summer Schools since 2009. Methods: The Youth Forum OU performed a survey in December 2014 to answer the research question on the basis of an internet-based poll of the student participants in all Summer Schools between 2009 and 2014. Following data cleansing, 121 students and former students were included in the survey. Results: Seventy-two completed questionnaires were collected and included in the evaluation. The survey included 40 % of Summer School participants, with a mean age of 27.3 years (SD ± 2.95); 50 % were female. Participation in the Summer School helped 50 % of the respondents to decide to start advanced study in orthopaedics and/or traumatology (OU). One third of these Summer School participants had already finished a university degree; 100 % are now residents in orthopaedics and/or traumatology. Regardless of prior plans, 87.2 % of participants are now residents in OU. Thirty-three are still students: 78.8 % have already decided to work in OU. The survey also served to identify the factors positively and negatively associated with OU. Unfavourable factors included the reputation of OU, and the difficulty of reconciling family and work. Favourable factors included surgical work and personal experience during university studies. Discussion: The aim of this study was to evaluate whether the efforts of the Youth Forum OU, the German Society for Orthopaedics and Traumatology (DGOU) and the local hospitals lead to increased interest in OU. The answer to this question is positive. This is particularly true for those students who did not plan to become an orthopaedic or trauma surgeon before participating in a Summer School. In conclusion, the efforts to recruit residents for OU by using Summer Schools were successful. Moreover, this research offers approaches to counteract the loss of attractiveness of OU.

[Daily routine in orthopedics and traumatology - results of a nationwide survey of residents]. / Der klinische Alltag in Orthopädie und Unfallchirurgie - Ergebnisse einer nationalen Umfrage unter Assistenzärzten in O und U.

BACKGROUND: The subject orthopedics and traumatology suffers by a loss of attractiveness which results in a lack of young blood. The aim of this study of the Youth Forum of the German Society of Orthopedics and Traumatology (DGOU) is to register the working conditions of residents in orthopedics. MATERIAL AND METHODS: In the months September and October 2013 we performed a survey on members of the following German societies: German Society of Orthopedics and Traumatology (DGOU), German Society of Traumatology (DGU) and the German Society of Orthopedics and Orthopedic Surgery (DGOOC), (age < 40). Our questionnaire includes 15 questions. RESULTS: We achieved 28,9 % (n = 331) answered questionnaires. The mean working time per week is 55 hours. 73 % of all participants do more than 5 emergency services per month. 52 % are more than 3 times on duty for 24 hours. Only 13 % of all residents have well ordered working hours. Normally working time is divided into three parts: one third for bureaucracy, one for operation theatre and the last for other activities (e.g. ward round). 35,6 % do only one surgery per week, 12 % do not perform any surgeries. An annual report is performed only in 45 %. A structured concept of training only exists in 16 % of all hospitals. In addition to clinical work 45 % are involved in scientific projects, mostly in their spare-time. Finally 58 % of all surgeons would still recommend orthopedics and traumatology. CONCLUSION: In order to maintain orthopedics and traumatology as an attractive it is necessary to implement flexible working time models and to reorganize and improve training-concepts.

[Arthroplasty for fractures of the femur near the hip joint]. / Endoprothetik bei hüftgelenknahen Femurfrakturen.

The incidence of proximal fractures of the femur will increase with the demographic change in the German population. Besides osteosynthesis, which in most cases of femoral neck, pertrochanteric and femoral head fracture is the method of choice, arthroplasty of the hip is likewise an established therapy. Indications are dislocated femoral neck fractures of the elderly. But there are good results for arthroplasty after proximal femoral fractures in younger active patients as well, when the fracture was not recognized or treated immediately. The outcome of hip arthroplasty after fracture is influenced by the elderly and unhealthy patient himself and the difficult planning and operation conditions due to fracture and its morphology. Most important for the best result are an interdisciplinary preparation of the patient and a well-planned surgery. In these cases common complications like thromboembolism, massive intraoperative blood loss and general infections like urinary tract infection can be reduced. For hip arthroplasty after fracture total hip replacement as well as hemiarthroplasty with bipolar prosthesis should be considered. The implant chosen and the implantation technique with or without bone cement has to be determined. Facts like the general state of health, biological age, level of activity and comorbidities should be taken into account appropriately.

Randomised clinical trial: a herbal preparation of myrrh, chamomile and coffee charcoal compared with mesalazine in maintaining remission in ulcerative colitis--a double-blind, double-dummy study.

BACKGROUND: The herbal treatment with myrrh, dry extract of chamomile flowers and coffee charcoal has anti-inflammatory and antidiarrhoeal potential and might benefit patients with UC. Aminosalicylates are used as standard treatment for maintaining remission in ulcerative colitis (UC). AIM: To compare the efficacy of the two treatments in maintaining remission in patients with ulcerative colitis. METHODS: We performed a randomised, double-blind, double-dummy study over a 12-month period in patients with UC. Primary endpoint was non-inferiority of the herbal preparation as defined by mean Clinical Colitis Activity Index (CAI-Rachmilewitz). Secondary endpoints were relapse rates, safety profile, relapse-free times, endoscopic activity and faecal biomarkers. RESULTS: A total of 96 patients (51 female) with inactive UC were included. Mean CAI demonstrated no significant difference between the two treatment groups in the intention-to-treat (P = 0.121) or per-protocol (P = 0.251) analysis. Relapse rates in total were 22/49 patients (45%) in the mesalazine treatment group and 25/47 patients (53%) in the herbal treatment group (P = 0.540). Safety profile and tolerability were good and no significant differences were shown in relapse-free time, endoscopy and faecal biomarkers. CONCLUSIONS: The herbal preparation of myrrh, chamomile extract and coffee charcoal is well tolerated and shows a good safety profile. We found first evidence for a potential efficacy non-inferior to the gold standard therapy mesalazine, which merits further study of its clinical usefulness in maintenance therapy of patients with ulcerative colitis. EudraCT-Number 2007-007928-18.

Willow bark extract STW 33-I in the long-term treatment of outpatients with rheumatic pain mainly osteoarthritis or back pain.

STUDY OBJECTIVE: Efficacy and safety of willow bark extract for pain reduction in patients suffering from musculoskeletal disorders (MSD) has been shown in clinical short term trials. Therefore this observational study over 6 months should evaluate patterns of treatments like mono- or combinations therapy, dosage and safety during long-term treatment under pragmatic conditions with the aqueous willow bark extract STW 33-I, (Proaktiv(®); drug-extract-ratio 16-23:1). PATIENTS AND METHODS: The patients were treated with STW 33-I; comedication with other NSAIDs and opioids was allowed. An extensive case report form including pain questionnaires and patient diary was used for outcome evaluation. RESULTS: Four hundred and thirty-six patients with rheumatic pain mainly due to osteoarthritis (56.2%) and back pain (59.9%) were included. During the study the mean reductions from baseline value 58.4±22.6-31.8±22.5 after 24 weeks in the pain intensity scale (VAS 0-100mm) were significant even after 3 weeks with a reduction by 26 mm (45.6% of the baseline value) at the end of the study. The relative reductions of the weekly means of the daily patient self-rated scores of the pain (6-point Likert-scales) were between 33% and 44% of the baseline values during the course of the study. We present results of subgroups according their analgetic/antiphlogistic comedication. The distribution and specification of the main adverse events and the ratings of the treatment showed a good tolerability. No relevant drug interactions were reported. CONCLUSION: These data suggest that STW 33-I can be used as a basic treatment in the long-term therapy of painful musculoskeletal disorders and that it can be combined with NSAIDs and opioids if necessary.

[Further training in the faculty of orthopedics and trauma surgery. Outstanding, average or insufficient?]. / Weiterbildung im Fach Orthopädie und Unfallchirurgie. Mustergültig, mittelmäßig oder mangelhaft?

A well structured and executed and practical residency program is important to secure a sufficient number of well trained orthopedic surgeons in the future. Some of the residents, however, see substantial shortcomings here. Additionally, orthopedic residency programs struggle to be a valid alternative for graduated medical students when comparing them to residency programs in other medical specialities or alternative job options. In improving the current situation program directors as well as residents must play a key role. A rapid improvement of structural shortcomings of German residency programs does not only provide an advantage in recruiting new residents now, but may also help to maintain the high quality in orthopedic health care in the future.

[Compatibility of science and clinical aspects. Between realism and utopia]. / Vereinbarkeit von Wissenschaft und Klinik. Zwischen Realismus und Utopie.

The working environment for young residents in orthopedic surgery has changed tremendously over the past 10 years. Due to cumulative clinical requirements and increasing demands on work-life balance research activity has become less attractive. Successful incorporation of research into the career of residents is a challenging project for the future. The young forum of the German Association for Orthopedics and Traumatology (DGOU) provides different approaches to enhance the quality of research and to help young orthopedists and trauma surgeons.

[How many generalists and how many specialists does orthopedics and traumatology need?]. / Wie viel Generalist und wie viel Spezialist braucht die Orthopädie und Unfallchirurgie?

The training in orthopedic and trauma surgery has changed significantly with the introduction of the new residency program. The contents taught have already been reduced in breadth and the current developments in the outpatient and particularly in the clinical landscape also contribute to increasing specialization. This trend favors structures in which comprehensive medical care for the population in Germany in orthopedic and trauma surgery appears to be endangered and in which the future efforts for e.g. polytraumatised patients need to be questioned. The Young Forum of the German Society for Orthopedics and Traumatology actively accompanies a discussion about the necessity and value of generalists to ensure the level of care in Germany in addition to the specialists.

The potential of implant augmentation in the treatment of osteoporotic distal femur fractures: a biomechanical study.

PURPOSE: Osteoporotic fractures of the distal femur are an underestimated and increasing problem in trauma and orthopaedic surgery. Therefore, this study investigates the biomechanical potential of implant augmentation in the treatment of these fractures. METHODS: Twelve osteoporotic surrogate distal femora were randomly assigned to the augmented or non-augmented group. All specimens were fixed using the LCP DF. In the augmented group additionally 1ml Vertecem V+ was injected in each screw hole before screw positioning. The construct represents an AO 33 A3 fracture. Biomechanical testing was performed as sinusoidal axial loading between 50 and 500N with 2Hz for 45,000 cycles, followed by loading between 50 and 750N until failure. RESULTS: The augmented group showed significant higher axial stiffness (36%). Additionally the displacement after 45,000 cycles was 3.4 times lower for the augmented group (0.68±0.2mm vs. 2.28±0.2mm). Failure occurred after 45,130 cycles (SD 99) in all of the non-augmented specimens and in two specimens of the augmented group after 69,675 cycles (SD 1729). Four of the augmented specimens showed no failure. The failure mode of all specimens in both groups was a medial cut-out. CONCLUSIONS: This study shows a promising potential of implant augmentation in the treatment of osteoporotic distal femur fractures.

[Treatment of periprosthetic and peri-implant fractures : modern plate osteosynthesis procedures]. / Versorgung periprothetischer und periimplantärer Frakturen : Moderne Plattenosteosyntheseverfahren.

Periprosthetic fractures are increasing not only due to the demographic development with high life expectancy, the increase in osteoporosis and increased prosthesis implantation but also due to increased activity of the elderly population. The therapeutic algorithms are manifold but general valid rules for severe fractures are not available. The most commonly occurring periprosthetic fractures are proximal and distal femoral fractures but in the clinical routine fractures of the tibial head, ankle, shoulder, elbow and on the borders to other implants (peri-implant fractures) and complex interprosthetic fractures are being seen increasingly more. It is to be expected that in the mid-term further options, such as cement augmentation of cannulated polyaxial locking screws will extend the portfolio of implants for treatment of periprosthetic fractures. The aim of this review article is to present the new procedures for osteosynthesis of periprosthetic fractures.

[Treatment of periprosthetic and peri-implant fractures : modern plate osteosynthesis procedures]. / Versorgung periprothetischer und periimplantärer Frakturen : Moderne Plattenosteosyntheseverfahren.

Periprosthetic fractures are increasing not only due to the demographic development with high life expectancy, the increase in osteoporosis and increased prosthesis implantation but also due to increased activity of the elderly population. The therapeutic algorithms are manifold but general valid rules for severe fractures are not available. The most commonly occurring periprosthetic fractures are proximal and distal femoral fractures but in the clinical routine fractures of the tibial head, ankle, shoulder, elbow and on the borders to other implants (peri-implant fractures) and complex interprosthetic fractures are being seen increasingly more. It is to be expected that in the mid-term further options, such as cement augmentation of cannulated polyaxial locking screws will extend the portfolio of implants for treatment of periprosthetic fractures. The aim of this review article is to present the new procedures for osteosynthesis of periprosthetic fractures.

Local delivery of growth factors using coated suture material.

The optimization of healing processes in a wide range of tissues represents a central point for surgical research. One approach is to stimulate healing processes with growth factors. These substances have a short half-life and therefore it seems useful to administer these substances locally rather than systemically. One possible method of local delivery is to incorporate growth factors into a bioabsorbable poly (D, L-lactide) suspension (PDLLA) and coat suture material. The aim of the present study was to establish a procedure for the local delivery of growth factors using coated suture material. Sutures coated with growth factors were tested in an animal model. Anastomoses of the colon were created in a rat model using monofilament sutures. These were either untreated or coated with PDLLA coating alone or coated with PDLLA incorporating insulin-like growth factor-I (IGF-I). The anastomoses were subjected to biomechanical, histological, and immunohistochemical examination. After 3 days the treated groups showed a significantly greater capacity to withstand biomechanical stress than the control groups. This finding was supported by the results of the histomorphometric. The results of the study indicate that it is possible to deliver bioactive growth factors locally using PDLLA coated suture material. Healing processes can thus be stimulated locally without subjecting the whole organism to potentially damaging high systemic doses.

Phase II trial on the effects of Silexan in patients with neurasthenia, post-traumatic stress disorder or somatization disorder.

Silexan, a novel lavender oil preparation for oral use, has been authorized in Germany for the treatment of states of restlessness during anxious mood. An open-label, exploratory trial was performed to assess the potential of the medicinal product in the treatment of restlessness caused by anxiety as related to several disorders. Outcome measures included the Symptom Checklist-90-Revised (SCL-90-R), von Zerssen's Depression Scale (D-S), the 36-item Short Form Health Survey Questionnaire (SF-36), and a sleep diary. 50 male and female patients with neurasthenia (ICD-10 F48.0), post-traumatic stress disorder (PSD; F43.1), or somatization disorder (F45.0, F45.1) were included to receive 1 × 80 mg/day Silexan over 6 weeks; 47 could be analyzed for efficacy as full analysis set. At baseline, patients suffered from restlessness (96%), depressed mood (98%), sleep disturbances (92%), or anxiety (72%). Of those, resp. 62%, resp. 57%, resp.51%, resp. 62% showed improvements during treatment (p < 0.001). For all patients, mean D-S score decreased by 32.7% and SCL-90-R Global Severity Index by 36.4% as compared to baseline, (p < 0.001), while the SF-36 Mental Health Score increased by 48.2% (p < 0.001). Waking-up frequency (p = 0.002), Waking-up duration (p < 0.001) and morning tiredness (p = 0.005) were reduced, while efficiency of sleep (p = 0.018) and mood (p = 0.03) improved. Patients suffering from neurasthenia or PSD showed comparable improvements with most outcomes. The results in this trial justify to further investigate Silexan in disorders with accompanying restlessness caused by sub-threshold anxiety. Adverse reactions, predominantly gastrointestinal complaints, were judged as mild or moderate.

Silicea gastrointestinal gel improves gastrointestinal disorders: a non-controlled, pilot clinical study.

Aim. To investigate efficacy and tolerability of Silicea Gastrointestinal Gel in patients with gastrointestinal disorders. Methods. Open, prospective pivotal phase IV study with oral Silicea Gastrointestinal Gel over 6 weeks. Symptom score was part 1 of the Nepean Dyspepsia Index: 15 questions addressing intensity, frequency and impact of upper abdominal symptoms. 10 lower abdominal symptoms were asked analogously. A responder showed reduction of score of >50%. Results. 62 of 90 patients were evaluated per protocol. Upper and lower abdomen sum scores decreased already in the first three weeks (P < 0.001), which continued the following three weeks (P < 0.01). Mean symptom score for upper abdomen decreased from 52.2 ± 31.0 to 33.7 ± 28.7 (or by 35.4%; responder rate 37%); for lower from 39.6 ± 24.7 to 22.6 ± 21.7 (by 42.9%; responder rate 46%). Subgroups with diarrhea, IBS and GERD presented highest responder rates. 6% of patients reported adverse reactions with probable or possible relationship to the test product. Conclusions. Silicea Gastrointestinal Gel seems suitable beyond infectious acute gastrointestinal disorders. Responses are relevant for chronic functional disorders, but it remains unclear, how much of that might be placebo-effect. Controlled studies are recommended in gastrointestinal syndromes like IBS or GERD.

[Periprosthetic fractures. An interdisciplinary challenge]. / Periprothetische Frakturen. Eine interdisziplinäre Herausforderung.

Demographic changes and rising numbers of implanted prostheses accompanied by increasing demands on mobility and activities of the elderly will lead to an increasing number of periprosthetic fractures in the future. Poor bone quality, geriatric comorbidities and multiple prostheses result in an increased risk for this type of fracture in the old patient. Management of these patients is challenging and demanding and needs an interdisciplinary approach. The present work describes the different aspects of periprosthetic fractures in the geriatric patient with regard to epidemiology, risk factors, prevention and treatment options.