[Attitude of health care workers towards SARS-CoV-2 vaccination]. / Einstellung von Pflegekräften zur SARS-CoV-2-Impfung : Eine strukturierte Umfrage in Kliniken in Deutschland.

OBJECTIVES: Attitude of health care workers (HCW), namely registered nurses, towards SARS-CoV-2 vaccination and compulsory vaccination. METHOD: In a structured anonymous scientific survey from January 29 to April 26, 2021 a questionnaire was sent to 72 heads of orthopedic and trauma departments. The doctors were asked to distribute and recollect the questionnaire after obtaining informed consent from the hospital administration, the nursing management and the works council. Descriptive statistics were used to explain the results. RESULTS: 355 answers from 5 departments were evaluated. In 65 out of 72 hospitals the top managers of either hospital or nursing administration or the works council declined participation, 2 heads of department were not interested. 50,7% of HCW were already vaccinated or had a scheduled appointment for vaccination, 14,9% had not yet made up their mind and 34,4% refuse vaccination. The majority of HCW vote against compulsory vaccination (47,6%), less than a quarter approves it (23,4%). CONCLUSION: The willingness to vaccinate was extremely low in this survey. The main reason for refusal to vaccinate is fear of side effects, so an information campaign should primarily focus on this topic.

Perioperative multi-system optimization protocol in elderly hip fracture patients: a randomized-controlled trial.

PURPOSE: Hip fractures in elderly patients are associated with increased postoperative morbidity and mortality. We evaluated whether a perioperative multi-system optimization protocol can reduce postoperative complications in these patients. METHODS: Immediately after diagnosis of hip fracture, patients ≥ 60 yr were randomized to an intervention or control group. Patients in the intervention group were admitted to our postanesthesia care unit where they were treated with goal-directed hemodynamic management, optimized pain therapy, oxygen therapy, and optimized nutrition. Patients in the control group were managed according to our usual standard of care on a regular ward. Postoperative complications during hospital stay included pre-determined cardiovascular, respiratory, neurologic, renal, or surgical events. RESULTS: The incidence of at least one postoperative complication (primary outcome) was seen in 32 of 65 (49%) controls compared with 24 of 62 (39%) in the intervention group (relative risk [RR], 0.79; 95% confidence interval [CI], 0.53 to 1.17; P = 0.23). The secondary unadjusted outcomes showed that patients in the intervention group received more Ringer's acetate compared with controls (median difference, 1.3 L; 95% CI, 0.6 to 2.1 L; P < 0.001), had more frequently a mean arterial pressure > 70 mmHg (57% control vs 75% intervention; median percentage difference, 16%; 95% CI, 7 to 25%; P = 0.001), better pain control (numeric rating scale < 4 at all postoperative measurements; 25% control vs 81% intervention; RR, 0.26; 95% CI, 0.15 to 0.43; P < 0.001), and possibly a lower incidence of acute renal failure (RR, 0.37; 95% CI, 0.14 to 0.98; P = 0.04). CONCLUSIONS: The implementation of a perioperative multi-system optimization protocol algorithm did not significantly reduce the risk of postoperative complications. Nevertheless, we likely over-estimated the potential treatment effect in our study design and thus were under-powered to show an effect. TRIAL REGISTRATION: Clinicaltrials.gov (NCT01673776). Registered 23 August, 2012.

Influence of Absorbable Calcium Sulfate-Based Bone Substitute Materials on Human Haemostasis-In Vitro Biological Behavior of Antibiotic Loaded Implants.

Calcium sulfate (CS) formulations are frequently implanted as antibiotically impregnated bone substitutes in orthopedic and trauma surgery to prevent or treat bone infections. Calcium ions have been discussed as candidates to accelerate blood coagulation. The goal of this study is to evaluate substance-specific influences of CS formulations on blood coagulation. Specific ELISAs were conducted to determine markers of activated blood coagulation after incubation of human blood with CS beads. Additionally, wettability with freshly drawn human blood was measured. Three different types of CS bone substitute beads were compared (CS dihydrate with tripalmitin, containing Gentamicin (Herafill®-G: Group A) or Vancomycin (CaSO4-V: Group B); and a CS hemihydrate with Tobramycin (Osteoset®: Group C)). Examinations were performed by ELISA assays for F1+2, FXIIa and C3a. Our results prove that none of the CS preparations accelerated single specific assays for activated coagulation markers. This allows the conclusion that neither Herafill®-G (CaSO4-G) nor CaSO4-V alter haemostasis negatively. Blood samples incubated with Osteoset® display an elevated F1+2-activity. The addition of tripalmitin in Herafill®-G shifts the original into a significantly hydrophobic formulation. This was additionally proven by contact angle examination of the three substances with freshly drawn human blood, showing that acceleration of plasmatic coagulation is hindered by lipids and induced by surface effects caused by presence of rapidly soluble calcium ions in the Osteoset® preparation.

Polyaxial locking plates in treating distal humeral fractures: a comparative randomized trial for clinical outcome.

BACKGROUND: Management of distal humeral fractures remains to be one of the most challenging aspects in trauma surgery. Low profile plating systems with variable angle screw fixation represent a crucial advancement to the established angular stable locking plates with considerable attention in current research. The aim of the prospective randomized trial was to review the preliminary results and patients' outcome following treatment with these newly developed implants and to rule out potential differences in fracture treatment of two different plating systems. METHODS: Twenty patients with distal humeral fractures (AO 13-A1 - AO 13-C3) were included in the current study since 2014. After completing the randomization plan, patients were distributed into two groups for different variable angle locking plates (DePuy Synthes® VA-LCP vs. Medartis® Aptus Elbow). Functional elbow scoring (ROM, MEPS, QuickDASH) served as primary outcome parameter, while radiological fracture consolidation served as secondary outcome parameter. Follow-ups were conducted 6 weeks, 12 weeks, 6 months and 12 months after the operation. RESULTS: Seventeen of 20 patients (85%) concluded all follow-up examinations. Postoperative elbow extension deficiencies showed significant differences between the two groups in all follow-up examinations with a mean of Ø 18 +/- 7.4 degrees in the DePuy Synthes® VA-LCP group compared to a mean of Ø 6.5 +/- 7.5 degrees in the Medartis® Aptus Elbow group (p = 0.002) 12 months postoperatively. Functional scoring showed a disparate pattern. The Medartis® Aptus Elbow group achieved significantly better MEP scores during follow-up. However, the analysis of the QuickDash revealed better results of the DePuy Synthes® VA-LCP group in the first half and better results of the Medartis® Aptus Elbow group in the second half of the follow-up examination instead. CONCLUSIONS: Considering the complexity of distal humeral fractures, the usage of anatomically preshaped low profile variable angle locking plates for operative treatment leads to good clinical results. Even though there might be some advances of the Medartis® Aptus Elbow plating system concerning postoperative ROM and elbow function, a consistent difference in the overall clinical outcome between the two plating systems could not be detected. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT03272490 Retrospectively Registered 1. September 2017.

Malpositioned olecranon fracture tension-band wiring results in proximal radioulnar synostosis.

BACKGROUND: Tension-band wiring (TBW) is a well-established fixation technique for two-part, transverse fracture types of the olecranon. However, complication rates up to 80 % are reported. By reporting on the enormous impact on the patient if failed the aim of the present report was to emphasize the importance of correct K wire positioning in TBW. CASE PRESENTATION: We present the case of a 49-year-old woman who suffered from a radioulnar synostosis of the forearm due to malpositioned K wires after TBW treatment. The patient was treated by heterotopic bone resection supported by ossification prophylaxis (radiotherapy and Indomethacin). At follow-up of 12 months after revision surgery, elbow motion was unrestricted with a strength grade 5/5. The patient was free of pain and reported no restrictions in daily as well as sporting activities. Radiologic assessment showed no recurrence of heterotopic bone tissue. CONCLUSION: Intraoperative radiographic and clinical examination of the elbow is highly recommended to identify incorrect hardware positioning and, therefore, to avoid serious postoperative complications in TBW.

Tumor Growth Inhibition via Occlusion of Tumor Vasculature Induced by N-Terminally PEGylated Retargeted Tissue Factor tTF-NGR.

tTF-NGR retargets the extracellular domain of tissue factor via a C-terminal peptide GNGRAHA, a ligand of the surface protein aminopeptidase N (CD13) and upon deamidation of integrin αvß3, to tumor vasculature. tTF-NGR induces tumor vascular infarction with consecutive antitumor activity against xenografts and selectively inhibits tumor blood flow in cancer patients. Since random PEGylation resulted in favorable pharmacodynamics of tTF-NGR, we performed site-directed PEGylation of PEG units to the N-terminus of tTF-NGR to further improve the antitumor profile of the molecule. Mono-PEGylation to the N-terminus did not change the procoagulatory activity of the tTF-NGR molecule as measured by Factor X activation. Experiments to characterize pharmacokinetics in mice showed a more than 1 log step higher mean area under the curve of PEG20k-tTF-NGR over tTF-NGR. Acute (24 h) tolerability upon intravenous application for the mono-PEGylated versus non-PEGylated tTF-NGR compounds was comparable. PEG20k-tTF-NGR showed clear antitumor efficacy in vivo against human tumor xenografts when systemically applied. However, site-directed mono-PEGylation to the N-terminus does not unequivocally improve the therapeutic profile of tTF-NGR.

Anticancer therapy by tumor vessel infarction with polyethylene glycol conjugated retargeted tissue factor.

tTF-NGR consists of the extracellular domain of tissue factor and the peptide GNGRAHA, a ligand of the surface protein aminopeptidase N and of integrin αvß3. Both surface proteins are upregulated on endothelial cells of tumor vessels. tTF-NGR shows antitumor activity in xenografts and inhibition of tumor blood flow in cancer patients. We performed random TMS(PEG)12 PEGylation of tTF-NGR to improve the antitumor profile of the molecule. PEGylation resulted in an approximately 2-log step decreased procoagulatory activity of the molecule. Pharmacokinetic studies in mice showed a more than 1-log step higher mean area under the curve. Comparison of the LD10 values for both compounds and their lowest effective antitumor dose against human tumor xenografts showed an improved therapeutic range (active/toxic dose in mg/kg body weight) of 1/5 mg/kg for tTF-NGR and 3/>160 mg/kg for TMS(PEG)12 tTF-NGR. Results demonstrate that PEGylation can significantly improve the therapeutic range of tTF-NGR.

Monocytes do not transdifferentiate into proper osteoblasts.

Recent publications suggested that monocytes might be an attractive cell type to transdifferentiate into various cellular phenotypes. Aim was, therefore, to evaluate the potential of blood monocytes to transdifferentiate into osteoblasts. Monocytes isolated from peripheral blood were subjected to two previously published treatments to obtain unique, multipotent cell fractions, named programmable cells of monocytic origin (PCMOs) and monocyte-derived mesenchymal progenitor cells (MOMPs). Subsequently, MOMPs and PCMOs were treated with osteogenic differentiation medium (including either vitamin D or dexamethasone) for 14 days. Regarding a variety of surface markers, no differences between MOMPs, PCMOs, and primary monocytes could be detected. The treatment with osteogenic medium neither resulted in loss of hematopoietic markers nor in adoption of mesenchymal phenotype in all cell types. No significant effect was observed regarding the expression of osteogenic transcription factors, bone-related genes, or production of mineralized matrix. Osteogenic medium resulted in activation of monocytes and appearance of osteoclasts. In conclusion, none of the investigated monocyte cell types showed any transdifferentiation characteristics under the tested circumstances. Based on our data, we rather see an activation and maturation of monocytes towards macrophages and osteoclasts.

New method for detection of complex 3D fracture motion--verification of an optical motion analysis system for biomechanical studies.

BACKGROUND: Fracture-healing depends on interfragmentary motion. For improved osteosynthesis and fracture-healing, the micromotion between fracture fragments is undergoing intensive research. The detection of 3D micromotions at the fracture gap still presents a challenge for conventional tactile measurement systems. Optical measurement systems may be easier to use than conventional systems, but, as yet, cannot guarantee accuracy. The purpose of this study was to validate the optical measurement system PONTOS 5M for use in biomechanical research, including measurement of micromotion. METHODS: A standardized transverse fracture model was created to detect interfragmentary motions under axial loadings of up to 200 N. Measurements were performed using the optical measurement system and compared with a conventional high-accuracy tactile system consisting of 3 standard digital dial indicators (1 µm resolution; 5 µm error limit). RESULTS: We found that the deviation in the mean average motion detection between the systems was at most 5.3 µm, indicating that detection of micromotion was possible with the optical measurement system. Furthermore, we could show two considerable advantages while using the optical measurement system. Only with the optical system interfragmentary motion could be analyzed directly at the fracture gap. Furthermore, the calibration of the optical system could be performed faster, safer and easier than that of the tactile system. CONCLUSION: The PONTOS 5 M optical measurement system appears to be a favorable alternative to previously used tactile measurement systems for biomechanical applications. Easy handling, combined with a high accuracy for 3D detection of micromotions (≤ 5 µm), suggests the likelihood of high user acceptance. This study was performed in the context of the deployment of a new implant (dynamic locking screw; Synthes, Oberdorf, Switzerland).

A new mechanism preventing proarrhythmia in chronic heart failure: rapid phase-III repolarization explains the low proarrhythmic potential of amiodarone in contrast to sotalol in a model of pacing-induced heart failure.

AIMS: Life-threatening arrhythmias are a major problem in chronic heart failure (CHF). The aim of the present study was to investigate the mechanism underlying the low proarrhythmic potential of amiodarone in a model of pacing-induced heart failure. METHODS AND RESULTS: Heart failure was induced in 35 female rabbits by rapid ventricular pacing, resulting in a significant decrease of ejection fraction. Thirty-four rabbits were sham-operated. In 17 of 35 CHF-rabbits and 20 of 34 'sham'-rabbits, amiodarone (50 mg/kg/day) was fed for 6 weeks. Eight monophasic action potentials and a simultaneously recorded 12-lead electrocardiogram showed prolongation of QT-interval and action potential duration (APD(90)) in all failing hearts (P< 0.05). Amiodarone pre-treatment led to a prolongation of APD(90) (+19 ms) as compared with sham-controlled hearts but showed only a marginal effect on APD(90) in failing hearts. Infusion of sotalol (50-100 µM) led to a significant prolongation of APD(90) in sham and a further prolongation of APD(90) in failing hearts [+55 ms (50 µM); +70 ms (100 µM); P< 0.01 as compared with sham hearts]. Sotalol led to a triangular action potential configuration in sham and failing hearts, whereas amiodarone did not cause triangularization but caused a rapid phase-III repolarization. Moreover, amiodarone did not increase dispersion of repolarization either in sham or in failing hearts. Infusion of sotalol led to a significant increase in dispersion of repolarization in sham (+29 ms) and a further increase in failing hearts (+67 ms; P< 0.05). CONCLUSION: Chronic amiodarone results in a rapid phase-III-repolarization and does not increase dispersion of repolarization. These electrophysiological findings are present in healthy hearts and are preserved in heart failure. This contributes to the low proarrhythmic potential of amiodarone in heart failure.

TGF-ß1 as possible link between loss of bone mineral density and chronic inflammation.

BACKGROUND: The TGF family plays a key role in bone homeostasis. Systemic or topic application of proteins of this family apparently positively affects bone healing in vivo. However, patients with chronic inflammation, having increased TGF-ß(1) serum-levels, often show reduced bone mineral content and disturbed bone healing. Therefore, we wanted to identify intracellular mechanisms induced by chronic presence of TGF-ß(1) and their possible role in bone homeostasis in primary human osteoblasts. METHODOLOGY/PRINCIPAL FINDINGS: Osteoblasts were isolated from femur heads of patients undergoing total hip replacement. Adenoviral reporter assays showed that in primary human osteoblasts TGF-ß(1) mediates its signal via Smad2/3 and not Smad1/5/8. It induces proliferation as an intermediate response but decreases AP-activity and inorganic matrix production as a late response. In addition, expression levels of osteoblastic markers were strongly regulated (AP↓; Osteocalcin↓; Osteopontin↑; MGP↓; BMP 2↓; BSP2↓; OSF2↓; Osteoprotegerin↓; RANKL↑) towards an osteoclast recruiting phenotype. All effects were blocked by inhibition of Smad2/3 signaling with the Alk5-Inhibitor (SB431542). Interestingly, a rescue experiment showed that reduced AP-activities did not recover to base line levels, even 8 days after stopping the TGF-ß(1) application. CONCLUSIONS/SIGNIFICANCE: In spite of the initial positive effects on cell proliferation, it is questionable if continuous Smad2/3 phosphorylation is beneficial for bone healing, because decreased AP-activity and BMP2 levels indicate a loss of function of the osteoblasts. Thus, inhibition of Smad2/3 phosphorylation might positively influence functional activity of osteoblasts in patients with chronically elevated TGF-ß(1) levels and thus, could lead to an improved bone healing in vivo.

Compartment syndrome of the thigh. A case report with delayed onset after stable pelvic ring fracture and chronic anticoagulation therapy.

Compartment syndrome of the thigh is a rare occurrence potentially leading to devastating functional restrictions. There is a wide spectrum of reported conditions leading to increased tissue pressure in the thigh possibly resulting in a compartment syndrome, ranging from deep venous thrombosis to blunt injuries and femoral fractures. We report a case of a delayed development of a compartment syndrome of the thigh secondary to an undisplaced anterior pelvic ring fracture and chronic anticoagulation therapy in a 94-year-old woman. Regarding anticoagulation therapy there are numerous reports about the spectrum of bleeding complications during therapy, however this severe complication has to our knowledge not been reported previously. Treatment consisted in immediate fasciotomy and subsequently secondary wound closure.

Gentamycin delivered from a PDLLA coating of metallic implants: In vivo and in vitro characterisation for local prophylaxis of implant-related osteomyelitis.

Locally applied antibiotics support prophylaxis of highly feared implant associated infections. Implant coatings with poly(D,L-lactide) (PDLLA)/gentamicin seem to be a promising approach. Aims of this study were to analyse the release kinetics of gentamicin in vivo, in vitro, to analyse the antibacterial efficacy,the resistance development and its impact on osteoblasts. For the in vitro release experiments titanium implants were coated with PDLLA/gentamicin and the antibiotic release in aqueous solution was analysed at 20 time points (from 10 s to 110 days). For the in vivo experiments PDLLA/gentamicin-coated kirschner wires were implanted in the tibiae of 18 rats. Gentamicin concentration in the bone was analysed at several time points (n = 3 each, 1 h to 7 days). Bactericidal efficacy, bacterial adhesion on the implants and resistance development were tested. AP activity, cell count and CICP expression of osteoblasts were analysed. Gentamicin was released rapidly with an initial burst in aqueous solution and followed by a slow release. Similarly, in vivo gentamicin concentration reached a high peak initially followed by a decrease to a low level. No development of resistance was observed in the investigated setting, the antibacterial efficacy was not affected by the coating process and significantly fewer bacteria were attached to the implant. Osteoblasts were not negatively affected by the gentamicin released from the coating. PDLLA/gentamicin coating resulted in a desired antibiotic peak concentration within the bone. Bacterial adhesion was successfully prevented. No bacterial resistances were developed. This coating seems to be a suitable supplement for prophylaxis of implant-associated infections.

The dynamic locking screw (DLS) can increase interfragmentary motion on the near cortex of locked plating constructs by reducing the axial stiffness.

BACKGROUND: The plate-screw interface of an angular stable plate osteosynthesis is very rigid. So far, all attempts to decrease the stiffness of locked plating construct, e.g. the bridged plate technique, decrease primarily the bending stiffness. Thus, the interfragmentary motion increases only on the far cortical side by bending the plate. To solve this problem, the dynamic locking screw (DLS) was developed. MATERIALS AND METHODS: Comparison tests were performed with locking screws (LS) and DLS. Axial stiffness, bending stiffness and interfragmentary motion were compared. For measurements, we used a simplified transverse fracture model, consisting of POM C and an 11-hole LCP3.5 with a fracture gap of 3 mm. Three-dimensional fracture motion was detected using an optical measurement device (PONTOS 5 M/GOM) consisting of two CCD cameras (2,448 x 2,048 pixel) observing passive markers. RESULTS: The DLS reduced the axial stiffness by approximately 16% while increasing the interfragmentary motion at the near cortical side significantly from 282 microm (LS) to 423 microm (DLS) applying an axial load of 150 N. CONCLUSION: The use of DLS reduces the stiffness of the plate-screw interface and thus increases the interfragmentary motion at the near cortical side without altering the advantages of angular stability and the strength.

Medial migration of lag screw with intrapelvic dislocation in gamma nailing--a unique problem? A report of 2 cases.

Within the last decade, intramedullary nailing systems have gained popularity in the treatment of unstable fractures of the trochanteric region with good clinical results. However, these implants are not free of complications. Commonly reported treatment failures include implant cutout through the femoral neck, stress-derived femur fractures at the distal end of the nail, and secondary rotational displacement and varus deformity of the femoral neck and head. Only few reports exist on primary medial migration of the lag screw after treatment with intramedullary implants. We report on a rarely described complication in 2 patients who underwent osteosynthesis with a Gamma 3 nail (Stryker, Mahwah, NJ). Both patients presented with implant failures due to primary medial migration of the lag screw. Complete separation of the implant occurred, and the lag screw penetrated through the acetabulum into the pelvis. The patient's histories and course of treatment are reported. The literature on this topic is discussed.

Hemodynamic effects of titrated norepinephrine in healthy versus endotoxemic sheep.

In patients with sepsis and systemic inflammatory response syndrome, hemodynamic support is often complicated by a vascular hyporesponsiveness to exogenously administered norepinephrine. Although norepinephrine tachyphylaxis represents a significant clinical problem, the relationship between norepinephrine dosages and mean arterial pressure (MAP) in the presence of systemic inflammation is still not fully understood. This study was, therefore, designed as a prospective, controlled laboratory trial to elucidate the hemodynamic response to incremental norepinephrine doses in healthy and endotoxemic sheep. ANOVA demonstrated that a significantly higher mean infusion rate of norepinephrine was needed to increase MAP by 20 mmHg in endotoxemic versus healthy control sheep (P = 0.007). Whereas the goal-MAP was reached in 100% of healthy controls, it was achieved in only 80% during endotoxemia. Cardiac index increased significantly in healthy, but not in endotoxemic, sheep. Our findings confirm the presence of vascular hyporesponsiveness to norepinephrine in endotoxemia. In addition, this study demonstrates that the presence of systemic inflammation leads to an early hyporesponsiveness against norepinephrine which was caused by a drug-independent mechanism rather than a tachyphylaxis due to long-term administration of norepinephrine.

Dobutamine reverses the vasopressin-associated impairment in cardiac index and systemic oxygen supply in ovine endotoxemia.

INTRODUCTION: Arginine vasopressin (AVP) is increasingly used to treat sepsis-related vasodilation and to decrease catecholamine requirements. However, AVP infusion may be associated with a marked decrease in systemic blood flow and oxygen transport. The purpose of the present study was to evaluate whether dobutamine may be titrated to reverse the AVP-related decrease in cardiac index (CI) and systemic oxygen delivery index (DO2I) in an established model of ovine endotoxemia. METHODS: Twenty-four adult ewes were chronically instrumented to determine cardiopulmonary hemodynamics and global oxygen transport. All ewes received a continuous endotoxin infusion that contributed to a hypotensive-hyperdynamic circulation and death of five sheep. After 16 hours of endotoxemia, the surviving ewes (n = 19; weight 35.6 +/- 1.5 kg (mean +/- SEM)) were randomized to receive either AVP (0.04 Umin-1) and dobutamine (n = 8) or the vehicle (normal saline; n = 6) and compared with a third group treated with AVP infusion alone (n = 5). Dobutamine infusion was started at an initial rate of 2 microg kg-1min-1 and was increased to 5 and 10 microg kg-1 min-1 after 30 and 60 minutes, respectively. RESULTS: AVP infusion increased mean arterial pressure (MAP) and systemic vascular resistance index at the expense of a markedly decreased CI (4.1 +/- 0.5 versus 8.2 +/- 0.3 l min-1 m-2), DO2I (577 +/- 68 versus 1,150 +/- 50 ml min-1 m-2) and mixed-venous oxygen saturation (SvO2; 54.5 +/- 1.8% versus 69.4 +/- 1.0%; all p < 0.001 versus control). Dobutamine dose-dependently reversed the decrease in CI (8.8 +/- 0.7 l min-1 m-2 versus 4.4 +/- 0.5 l min-1 m-2), DO2I (1323 +/- 102 versus 633 +/- 61 ml min-1 m-2) and SvO2 (72.2 +/- 1.7% versus 56.5 +/- 2.0%, all p < 0.001 at dobutamine 10 microg kg-1 min-1 versus AVP group) and further increased MAP. CONCLUSION: This study provides evidence that dobutamine is a useful agent for reversing the AVP-associated impairment in systemic blood flow and global oxygen transport.

Prophylaxis and treatment of implant-related infections by antibiotic-coated implants: a review.

Implant-related infection is a feared complication in orthopedic and trauma surgery with tremendous consequences for the patient. To reduce this risk, administration of perioperative antibiotic prophylaxis is a routine procedure in orthopedic surgery. A local delivery system for antibiotics based on a polymer implant coating has been developed to optimize the prophylaxis. In an animal experiment, the efficacy of local prophylaxis of gentamicin was compared to a systemic single shot of gentamicin and to a combination of both administrations. The medullary cavities of rat tibiae were contaminated with Staphylococcus aureus and titanium K-wires were implanted into the medullary canals. For local antibiotic therapy, the implants were coated with poly(D,L-Lactide) (PDLLA) loaded with gentamicin. All the animals not treated with local and systemic application of the antibiotic developed osteomyelitis and all cultures of the implants tested positive for S. aureus. Onset of infection was prevented in 80-90% of animals treated with gentamicin-coated K-wires, with and without systemic prophylaxis. Gentamicin-coated intramedullary tibial nails are CE-certified for Europe and Canada and several patients have already been treated for implant-related infection. Up to now, eight patients with open tibia fractures have been treated with an unreamed tibial nail (UTN) coated with PDLLA and gentamicin. In the 1-year follow up, none of the patients developed an infection. A prospective randomized clinical documentation is currently in progress. So far, the results suggest that a local application of gentamicin from PDLLA-coated implants might support systemic antibiotic prophylaxis in preventing implant-associated osteomyelitis.

Collective review: bioactive implants coated with poly(D,L-lactide) and growth factors IGF-I, TGF-beta1, or BMP-2 for stimulation of fracture healing.

Demographic data reveal that due to the increasing aging of the population, complications with the musculoskeletal system will increase in the next years. One major problem in orthopedic and trauma surgery are the delayed healing or non-unions of long bone fractures. The exogenous application of growth factors can stimulate the bone healing to reduce these complications. Beside the choice of the optimal growth factor the application system is important. Therefore, we developed a new bioactive coating method for implants, which is based on a biodegradable poly(D,L-lactide) (coating thickness: 10 mum). This coating allows the incorporation of growth factors and the controlled release of these factors during the healing process without the need for further devices. The effect of different growth factors (IGF-I, TGF-beta1, and BMP-2) locally released from coated intramedullary implants on fracture healing was investigated with biomechanical and histological analysis in rats. All investigated growth factors stimulated the fracture healing as assessed with biomechanical tests and histological analysis. The local application of combined IGF-I and TGF-beta1 had the most stimulating effect on fracture healing, followed by the effect of BMP-2, IGF-I, and TGF-beta1 alone. Bioactive coating of biomechanical well-established implants can on the one hand stabilize the fracture and on the other hand stimulate healing processes to increase healing and to reduce the rate of complications.

Local protection for surgical implants.

In this issue of Chemistry & Biology, Jose and coworkers [1] describe the covalent attachment of vancomycin to a titanium surface. The tethered antibiotic is effective against S. aureus, suggesting that this material has the potential to complement clinical strategies for preventing infection following implant surgery.