[Diagnosis of periprosthetic joint infection : Development of an evidence-based algorithm by the work group of implant-associated infection of the AE-(German Society for Arthroplasty)]. / Diagnostik der periprothetischen Infektion : Entwicklung eines evidenzbasierten Algorithmus der Arbeitsgruppe implantatassoziierte Infektion der Arbeitsgemeinschaft Endoprothetik.

BACKGROUND: Prosthetic joint infections (PPI) will challenge orthopaedic surgeons and the health care system in the coming years. Evidence-based and reliable preoperative diagnostics are necessary for success in the field of revision arthroplasty. Especially the preoperative detection of PPI is important with respect to the treatment strategy. AIM: The aim of this study was to develop a detailed and structured standard operating procedure (SOP) to detect PPI preoperatively. METHODS: A systematic literature research was performed and relevant articles identified. After extracting the data, statistical calculations of sensitivity, specificity, positive/negative predictive value and positive/negative likelihood ratio were performed. The results were discussed and evaluated in four meetings analogously to standard Delphi rounds by the workgroup of implant-associated infections of the German AE (Arbeitsgemeinschaft Endoprothetik). An algorithm for the diagnostic approach according to ISO 5807 was made. RESULTS: The standardized algorithm combines a sequence of evidence-based procedures with detailed and structured main and additional criteria to every critical step in the diagnostic approach. CONCLUSION: The detection of PPI is of tremendous importance prior to revision arthroplasty and determines its success or failure. The diagnosis "prosthetic joint infection" requires a substantial change with respect to treatment concepts. The algorithm summarizes current literature and specialized expert opinions in a modern standardized format for a transparent diagnostic approach.

Novel method for reduction of virus load in blood plasma by sonication.

BACKGROUND: Aim of the present study is the evaluation of ultrasound as a physical method for virus inactivation in human plasma products prior to transfusion. Our study is focused on achieving a high level of virus inactivation simultaneously leaving blood products unaltered, measured by the level of degradation of coagulation factors, especially in third world countries where virus contamination of blood products poses a major problem. Virus inactivation plays an important role, especially in the light of newly discovered or unknown viruses, which cannot be safely excluded via prior testing. METHODS: Taking into account the necessary protection of the relevant coagulation activity for plasma, the basis for a sterile virus inactivation under shielding gas insufflation was developed for future practical use. Influence of frequency and power density in the range of soft and hard cavitation on the inactivation of transfusion-relevant model viruses for Hepatitis-(BVDV = bovine diarrhea virus), for Herpes-(SFV = Semliki Forest virus, PRV = pseudorabies virus) and Parvovirus B19 (PPV = porcine parvovirus) were examined. Coagulation activity was examined via standard time parameters to minimize reduction of functionality of coagulation proteins. A fragmentation of coagulation proteins via ultrasound was ruled out via gel electrophoresis. The resulting virus titer was examined using end point titration. RESULTS: Through CO2 shielding gas insufflation-to avoid radical emergence effects-the coagulation activity was less affected and the time window for virus inactivation substantially widened. In case of the non-lipidated model virus (AdV-luc = luciferase expressing adenoviral vector), the complete destruction of the virus capsid through hard cavitation was proven via scanning electron microscopy (SEM). This can be traced back to microjets and shockwaves occurring in hard cavitation. The degree of inactivation seems to depend on size and compactness of the type of viruses. Using our pre-tested and subsequently chosen process parameters with the exception of the small PPV, all model viruses were successfully inactivated and reduced by up to log 3 factor. For a broad clinical usage, protection of the coagulation activities may require further optimization. CONCLUSIONS: Building upon the information gained, an optimum inactivation can be reached via raising of power density up to 1200 W and simultaneous lowering of frequency down to 27 kHz. In addition, the combination of the two physical methods UV treatment and ultrasound may yield optimum results without the need of substance removal after the procedure.

Osteoinduction and -conduction through absorbable bone substitute materials based on calcium sulfate: in vivo biological behavior in a rabbit model.

Calcium sulfate (CS) can be used as an antibiotically impregnated bone substitute in a variety of clinical constellations. Antibiotically loaded bone substitutes find specific application in orthopedic and trauma surgery to prevent or treat bone infections especially in relation to open bone defects. However, its use as a structural bone graft reveals some concerns due to its fast biodegradation. The addition of calcium carbonate and tripalmitin makes CS formulations more resistant to resorption leaving bone time to form during a prolonged degradation process. The aim of the present study was the evaluation of biocompatibility and degradation properties of newly formulated antibiotically impregnated CS preparations. Three different types of CS bone substitute beads were implanted into the tibial metaphysis of rabbits (CS dihydrate with tripalmitin, containing gentamicin (Group A) or vancomycin (Group B); Group C: tobramycin-loaded CS hemihydrate). Examinations were performed by means of x-ray, micro-computed tomography (micro-CT) and histology after 4, 6, 8 and 12 weeks. Regarding biocompatibility of the formulations, no adverse reactions were observed. Histology showed formation of vital bone cells attached directly to the implanted materials, while no cytotoxic effect in the surrounding of the beads was detected. All CS preparations showed osteogenesis associated to implanted material. Osteoblasts attached directly to the implant surface and revealed osteoid production, osteocytes were found in newly mineralized bone. Group C implants (Osteoset®) were subject to quick degradation within 4 weeks, after 6-8 weeks there were only minor remnants with little osteogenesis demonstrated by histological investigations. Group A implants (Herafill®-G) revealed similar degradation within atleast 12 weeks. In contrast, group B implants (CaSO4-V) were still detectable after 12 weeks with the presence of implant-associated osteogenesis atlatest follow-up. In all of these preparations, giant cells were found during implant degradation on surface and inside of resorption lacunae. None of the analyzed CS preparations triggered contact activation. All implants demonstrated excellent biocompatibility, with implants of Group A and B showing excellent features as osteoconductive and -inductive scaffolds able to improve mechanical stability.

[Autologous fibula transplantation for reconstruction of bone defects]. / Die autologe Fibulatransplantation zur Rekonstruktion knöcherner Defekte.

The reconstruction of large bone defects following tumor resection, trauma or infection is difficult and subject to individual preferences of each surgeon. Free autologous fibula grafts are a reliable biological treatment method, whereas both a vascularised and a non-vascularised transplantation is possible. The use of either treatment option - vascularised or non-vascularised - is accompanied by individual advantages and/or disadvantages that should be taken into consideration during the preoperative planning process. Vascularised fibula transplants should be used especially for the reconstruction of large segmental defects and in patients, in whom adjuvant chemo- and/or radiation therapy is to be administered. Non-vascularised fibula grafts - which offer the advantage of a certain regeneration potential at the donor site as well as a shorter operation time - might be beneficial for bridging hemicortical defects and segmental defects with good soft tissue coverage.

[Hip dislocation after revision arthroplasty : Risk assessment and treatment strategies]. / Luxation nach Hüfttotalendoprothesenrevision : Analyse von Risikofaktoren und Lösungsstrategien.

With a dislocation rate of up to 35% after revision total hip arthroplasty (THA), instability is one of the major causes why this procedure fails. Independent factors for patients at risk are age, sex, and the type of revision needed. The surgical approach, implant choice, and positioning of the components are factors that the surgeon can influence to keep the dislocation rate low. Large femoral heads or double mobility (DM) cups can increase the stability of the joint. After detailed failure analysis, targeted use of different technical innovations enhances stability in revision THA and prevents further revisions.

[Importance of revision- and tumor-endoprosthetics in the treatment of periprosthetic fractures of the lower extremity]. / Stellenwert der Revisions- und Tumorendoprothetik bei der Versorgung periprothetischer Frakturen der unteren Extremität.

Periprosthetic fractures of hip and knee prostheses are gaining clinical significance due to the increasing numbers of of primary arthroplasties. Additionally, these fractures are often associated with poor bone quality or present in patients after multiple revision procedures and concomitant excessive bone defects precluding those patients to be adequately treated by conventional osteosynthesis. Revision implants provide a wide range of options for the treatment of these fractures in order to achieve good clinical results. In the acetabular region cavitary defects associated with periprosthetic fractures can be treated by the use of megacups. Extensive segmental defects and pelvic discontinuity necessitate the use of cups with additional iliac support or even customized implants. Proximal femoral fractures can usually be fixed with modular stems and diaphyseal anchorage. Periprosthetic knee joint fractures can be treated with revision implants with modular sleeves or augment-combinations allowing sufficient bridging of bony defects. Functional reconstruction or refixation of the extensor mechanism is of crucial importance.

[Epidemiology and prevention of prosthetic joint infection]. / Epidemiologie und Prophylaxe periprothetischer Infektionen.

BACKGROUND: Prosthetic joint infection (PJI) is challenging for patients and orthopedic surgeons and represents a great economic burden to the health care system. The growing number of primary and revision arthroplasty procedures in an aging society with demographic changes will increase the number of PJIs in the future. AIM: This article presents an overview of the epidemiology and prevention of PJI. METHOD: A selective literature review was performed focusing on evidence-based epidemiology, risk factors, and prevention of PJI. RESULTS: The total number of primary arthroplasty and septic revision procedures is increasing. The incidence of PJI is constant, although surgical techniques have improved over the years, with a multitude of possible preventive procedures for use before surgical treatment. This is most likely due to the increasing comorbidities and individual risk factors of the patient. Both endogenous and exogenous risk factors are known to be associated with PJI. Endogenous risk factors include diabetes, obesity, immunosuppression, oncological diseases, rheumatoid arthritis, previous or chronic infections, and bacteriuria. Exogenous risk factors include the extended duration of the operation, blood transfusion, and hypothermia. However, the facilities in the operating theatre or the use of iodine-impregnated incision drape seem to have no influence on the incidence of PJI. PROSPECT: The increasing number of arthroplasty procedures and the static incidence of PJI will result in an increase in the total number of PJIs in the next few years. In particular, the costs to the health care system of the treatment of PJI will emphasize further the need for the prevention of PJI. Individual risk factors should be optimized before arthroplasty requiring a close cooperation between the general practitioner and the orthopedic specialist.

[Septic endoprosthesis exchange : Preoperative diagnosis and reimplantation]. / Septischer Endoprothesenwechsel : Präoperative Diagnostik und Reimplantation.

BACKGROUND: The treatment of prosthetic joint infection (PJI) is truly challenging. Patients with infected arthroplasty face physical and psychosocial problems. Furthermore, treatment costs represent a tremendous socioeconomic burden. AIM: This article presents an overview of the preoperative diagnosis of PJI and one- or two-stage endoprosthetic exchange options. METHOD: A selective literature search was performed focusing on diagnostics and innovative surgical treatment concepts in PJI. RESULTS: The identification of the underlying pathogen is still the main focus in the diagnosis of PJI. State-of-the-art therapy for PJI with mature biofilm consists of implant removal with one- or two-stage exchange arthroplasty. One-stage exchange offers lower morbidity and improved functional outcome, whereas a two-stage procedure is, according to current knowledge, more favourable in terms of infection control. The novel short-term two-stage exchange regimen combines the advantages of both possibilities. DISCUSSION: Prosthetic joint infection represents a significant challenge for the othopaedic surgeon. Novel treatment options can help to improve outcome and lower the costs to the health care system.

[Synovial biomarkers for differential diagnosis of painful arthroplasty]. / Synoviale Biomarker für die Differenzialdiagnostik der schmerzhaften Endoprothese.

BACKGROUND: The diagnosis and treatment of periprosthetic joint infection (PJI) remain true clinical challenges. PJI diminishes therapeutic success, causes dissatisfaction for the patient and medical staff, and often requires extensive surgical revision(s). At the present time, an extensive multimodal algorithmic approach is used to avoid time- and cost-consuming diagnostic aberrations. However, especially in the case of the frequent and clinically most relevant "low-grade" PJI, the current diagnostic "gold standard" has reached its limits. EVALUATION: Synovial biomarkers are thought to close this diagnostic gap, hopefully enabling the safe differentiation among aseptic, (chronic) septic, implant allergy-related and the arthrofibrotic genesis of symptomatic arthroplasty. Therefore, joint aspiration for obtaining synovial fluid is preferred over surgical synovial tissue biopsy because of the faster results, greater practicability, greater patient safety, and lower costs. In addition to the parameters synovial IL-6, CRP, and leukocyte esterase, novel biomarkers such as antimicrobial peptides and other proinflammatory cytokines are currently highlighted because of their very high to excellent diagnostic accuracy. CONCLUSION: Independent multicenter validation studies are required to show whether a set of different innovative synovial fluid biomarkers rather than a few single parameters is favorable for a safe "one-stop shop" differential diagnosis of PJI.

[Periprosthetic infections of the hip joint : Clinical approach]. / Periprothetischer Infekt des Hüftgelenks : Klinisches Vorgehen.

BACKGROUND: Increasing rates of periprosthetic joint infections (PJI) will present orthopedic surgeons and the health care system with challenges in the next few years. New concepts in diagnostic and surgical pathways allow specialized centers to offer differentiated therapy of PJI. AIM: This article presents an overview of recent treatment concepts for PJI of the hip emphasizing diagnosis and the clinical approach. METHOD: A selective literature search was performed focusing on evidence-based concepts including diagnostics, surgical treatment, and biofilm active antibiotics. RESULTS: PJI of the hip are classified as mature biofilm or immature biofilm infections. The most important step in the diagnostic procedure is to identify the pathogen and its antimicrobial susceptibility. Preoperative joint aspiration and leukocyte count, differentiation, and microbiological culture should be standard. Arthroscopic biopsy may be necessary to identify the pathogen. Depending on the biofilm maturity and the antimicrobial susceptibility, implant retention or two-stage revisions should be performed. Combination of surgical therapy and biofilm-active antibiotics are of utmost importance for successful treatment. DISCUSSION: PJI represents a significant challenge for the orthopedic surgeon. Evidence-based and standardized clinical pathways are necessary for accurate and rapid diagnosis as well as patient-specific treatment concepts.

[Biopsies from bone and soft tissue sarcoma : a nationwide survey in Germany]. / Biopsie von Knochen- und Weichteilsarkomen : Eine deutschlandweite Umfrage.

AIM OF THE STUDY: A biopsy is an essential step in the diagnostic cascade of malignant bone and soft tissue tumors. The objective is always the extraction of a representative tissue specimen in line with the approach for the definitive operation. The aim of this study therefore was to assess the diagnostic approaches regarding the biopsy of tumors in orthopedic centers in Germany. MATERIAL AND METHODS: In total 60 hospitals with an orthopedic focus on tumors were contacted and provided with a newly developed questionnaire with 13 items regarding biopsy technique, indication criteria, execution, supportive imaging and histopathological results. Evaluation of the responses was performed by means of binary systems and proportional consent to every answer possibility was calculated. RESULTS: The results of the questionnaire showed that open biopsies are performed in all centers and in 72 % of the hospitals percutaneous techniques are additionally applied. The most important criterion for an open or percutaneous procedure was the tumor location (80 %). The indications for either technique are assessed by a tumor orthopedic consultant in 68 % of the centers and special imaging is applied in 36 % of the institutions. The approach for the biopsy is defined by the orthopedic surgeon in 88 %. Percutanous biopsies are carried out by interventional radiologists in 60 % of the centers. Open biopsies are performed by residents under supervision by a tumor orthopedic consultant in 88 %. The histopathological results are discussed in 88 % of the hospitals in an interdisciplinary tumor board and in 64 % patients are informed about the diagnosis in an outpatient clinic. CONCLUSIONS: Overall, biopsy of musculoskeletal tumors is performed according to the guidelines in most institutions. Only small differences were identified regarding the definition of the surgical approach and the application of imaging techniques during biopsy.

Mineralisation and mechanical strength of the subchondral bone plate of the inferior tibial facies.

BACKGROUND: The implantation of total ankle prosthesis is one of the most challenging operations in orthopaedic surgery. The main problem that surgeons face is the fixation of the total ankle prosthesis on the tibial side. The subchondral bone plate of the distal tibia is considered the strongest region on the inferior tibial facies. Based on information about the mineralisation of the subchondral bone plate, conclusions can be made concerning the mechanical stress, age-related changes, post-surgical biomechanical situations and regions of fixation. The aim of this study was to determine the correlation between the mineralisation of the subchondral bone plate and the topical mechanical strength. METHODS: By means of CT-osteoabsorptiometry, the distribution of mineralisation in the subchondral bone plate in 18 distal Tibiae was investigated. After removal of the cartilage of the facies articularis inferior, the mechanical strength of the joint surface was measured with an indentation apparatus. The linear regression of the mineralisation density and the maximal mechanical strength to penetrate the subchondral bone plate was determined. RESULTS: Our data showed a coefficient of determination between 0.75 and 0.97 and a coefficient of correlation between 0.86 and 0.97. The T test showed significance (P < 0.05). Furthermore, we demonstrated a bicentric distribution of mineralisation patterns. The maximal mineralisation was found ventromedially and mediolaterally on the joint surface. CONCLUSION: Our study shows good correlation of mineralisation and mechanical property of the inferior tibial facies. Therefore, as the results provide information on the topographical distribution of bone quality, they could be useful for the development of new fixation methods for total ankle prosthesis.

[Ligaments of the knee]. / Bänder des Kniegelenks.

The ligaments of the knee can be divided into four groups. Ventral reinforcements are the patellar retinaculae. The posteromedial complex stabilizes the valgus stress. It consists of the medial collateral ligament, the thickened posteromedial capsule and a branch of the tendon of the semimembranosus muscle as well as the oblique popliteal ligament. On the lateral side the posterolateral complex protects the knee against varus stress. Here the lateral collateral ligament, the tendon of the popliteus muscle and the so-called popliteofibular fibres work together. The cruciate ligaments control the contact between femoral condyles and tibial plateau during flexion-extension of the knee. They course between the two layers of the capsule, the membranous and the synovial layer.

Spontaneous intracerebral hemorrhage. Prognostic factors in 896 cases.

To determine the prognostic value of etiology and localization in spontaneous intracerebral hemorrhage, 896 patients with spontaneous intracerebral hemorrhage, as proven by CT, operation or autopsy, were retrospectively studied using univariate data analysis. Etiologies were hypertension in 63.5%, cerebrovascular malformations in 8.5% and abnormal hemostasis in 15% of the patients. In 23% no etiology was determined. Main localizations were cerebral lobes in 49.2%, basal ganglia in 34.4%, brain stem in 6.9%, cerebellum in 6.7% and primary intraventricular in 2.3% of the patients. Ventricular extension was present in 47.0%. A higher case fatality correlated with: 1) ventricular extension (P < 0.00001), 2) increasing age (P = 0.00005), 3) surgical treatment (P = 0.00010), 4) localization in basal ganglia (P = 0.0108) and 5) hypertension as only etiology (P = 0.01471). A lower case fatality was found in patients with cerebrovascular malformations (P = 0.00006) and when the hemorrhage was localized to the cerebral lobes (P = 0.0050). We conclude that etiology and localization are of prognostic value in spontaneous intracerebral hemorrhage.

A randomised controlled trial to evaluate the effects of flumazenil after midazolam premedication in outpatients undergoing colonoscopy.

The degree of sedation and amnesia, subjective assessment of awakening and side effects after intravenous injection of 3-4 mg midazolam and 1 mg flumazenil or placebo were studied directly after colonoscopy, and on the first and the eight day. A total of 91 patients were studied; 45 patients were given flumazenil and 46 patients a placebo. Five minutes after injection of the test drugs all 45 patients given flumazenil but only 38 patients given the placebo were alert (p = 0.006). All three response criteria (for sedation, amnesia and subjective assessment of awakening) were fulfilled by 84.4% of the patients given flumazenil and 45.7% of the patients given the placebo (p = 0.0002). Thirty minutes after injection of the test drugs dizziness, nausea, and fatigue were found in 3 patients given flumazenil and in 10 patients given placebo. One day after colonoscopy 9 of 45 patients (20%) given midazolam and flumazenil complained of fatigue and 9 of 46 patients (19.5%) given midazolam and placebo. Eight days (+/- 1 day) later two patients in each group complained of headache, nausea and fatigue. No patient developed phlebitis at the injection site. Flumazenil seems to be a safe and efficient drug for reversing the sedative effect of midazolam, premedication after colonoscopy. However, resedation due to the effects of midazolam may occur. Flumazenil thus permits administration of a higher dose of midazolam without prolongation of the surveillance time. Improved exploitation of time, space and nursing resources is thus possible without jeopardizing patient safety, although caution is necessary since patients may not be fit to resume all normal activities.

[Antagonizing the effect of midazolam by flumazenil in gastroscopy: results of a randomized double blind study]. / Zur Aufhebung der Wirkung von Midazolam durch Flumazenil bei der Gastroskopie: Ergebnisse einer randomisierten Doppelblindstudie.

The action and side effects of the benzodiazepine antagonist Flumazenil were evaluated and compared with placebo in a double blind parallel group randomized trial involving 40 patients having upper gastrointestinal endoscopy under Midazolam premedication. Flumazenil reversed the hypnotic effect of midazolam within a few minutes. The patients were alert, cooperative, oriented and had recall of events after endoscopy. The effects were better than placebo concerning alertness for up to 30 minutes after administration whereas drowsiness remained almost stable after placebo. Time to reach full alertness was shorter after Flumazenil compared with placebo (42 vs 62 minutes). There were no significant side effects. Flumazenil allows effective reversal of midazolam premedication after upper gastrointestinal endoscopy.