Stephan Arens

Fluorine-18 fluorodeoxyglucose PET in infectious bone diseases: results of histologically confirmed cases.

Abstract.The aim of this study was to evaluate the clinical use of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in acute and chronic osteomyelitis and inflammatory spondylitis. The study population comprised 21 patients suspected of having acute or chronic osteomyelitis or inflammatory spondylitis. Fifteen of these patients subsequently underwent surgery. FDG-PET results were correlated with histopathological findings. The remaining six patients, who underwent conservative therapy, were excluded from any further evaluation due to the lack of histopathological data. The histopathological findings revealed osteomyelitis or inflammatory spondylitis in all 15 patients: seven patients had acute osteomyelitis and eight patients had chronic osteomyelitis or inflammatory spondylitis. FDG-PET yielded 15 true-positive results. The tracer uptake correlated with the histopathological findings in each case. Bone scintigraphy performed in 11 patients yielded ten true-positive results and one false-negative result. Follow-up carried out on two patients revealed normal or clearly reduced tracer uptake, which correlated with a normalisation of clinical data. In early postoperative follow-up it was impossible to differentiate between postsurgical reactive changes and further infection using FDG-PET. It is concluded that acute and chronic osteomyelitis of the peripheral as well as the central skeleton can be detected using FDG-PET. Osteomyelitis can be differentiated from soft tissue infection surrounding the bone. Unlike computed tomography and magnetic resonance imaging, FDG-PET is not affected by metal implants used for fixing fractures. FDG-PET demonstrated promising initial results with respect to treatment monitoring. Nevertheless, in the early postoperative phase FDG-PET seems to be of limited value owing to unspecific tracer uptake.

Striated muscle microvascular response to silver implants: A comparative in vivo study with titanium and stainless steel.

Local microvascular perfusion is the primary line of defense of tissue against microorganisms and plays a considerable role in reparative processes. The impairment of the microcirculation by a biomaterial may therefore have profound consequences. Silver is known to have excellent antimicrobial activity and, although regional and systemic toxic effects have been described, silver is regularly discussed as an implant material in bone surgery. Because little is known about the influence of silver implants on the adjacent host tissue microvasculature, we studied in vivo nutritive perfusion and leukocytic response, and compared these results with those of the conventionally used materials titanium and stainless steel. Using the hamster dorsal skinfold chamber preparation and intravital microscopy, the implantation of a commercially pure silver sample led to a distinct and persistent activation of leukocytes combined with a marked disruption of the microvascular endothelial integrity, massive leukocyte extravasation, and considerable venular dilation. Whereas animals with stainless-steel implants showed a moderate increase in these parameters with a tendency to recuperate, titanium implants caused only a transient increase of leukocyte-endothelial cell interaction within the first 120 min and no significant change in macromolecular leakage, leukocyte extravasation and venular diameter. After 3 days, five of six preparations with silver samples showed severe inflammation and massive edema. Thus, the use of silver as an implant material should be critically judged despite its bactericidal properties. The implant material titanium seems to be well tolerated by the local vascular system and currently represents the golden standard.

Susceptibility to local infection in biological internal fixation

Abstract Resistance to local infection after fracture fixation with plate osteosynthesis may be influenced by the implantation technique. It is known that the extent of the surgical approach to the bone can compromise the local defence capacity. We have investigated susceptibility to infection after a local bacterial challenge in rabbit tibiae using either the open surgical approach for ‘biological’ internal fixation of standard 2.0 dynamic compression plates or the method of minimally invasive plate osteosynthesis (MIPO), a percutaneous, tunnelling insertion technique preserving the integrity of the overlying soft tissue. After the wounds had been closed, various concentrations of Staphylococcus aureus were injected in the direct vicinity of the implants. The infection rate for the open surgical technique was 38.5% and that for the MIPO technique, 25%. This difference is not statistically significant (P > 0.05) suggesting that resistance to local infection associated with the MIPO method is at least equivalent to the open approach for plate osteosynthesis.

Influence of the design for fixation implants on local infection: experimental study of dynamic compression plates versus point contact fixators in rabbits.

OBJECTIVES Comparison of infection resistance after local bacterial challenge associated with two different designs for fixation implants: the conventional dynamic compression plate (DCP) and the point contact fixator (PC-Fix). DESIGN Randomized, prospective study in experimental animals. Grouped sequential experimental procedure. Observation time was twenty-eight days, with twenty animals per group. SETTING Following surgery, animals were kept without restrictions in individual hutches. ANIMALS Forty White New Zealand rabbits. Thirty-eight animals, nineteen per group, were included in the final evaluation. INTERVENTION Under sterile conditions, specially manufactured titanium DCP or PC-Fix of identical dimensions were fixed to rabbit tibiae. After wound closure, different concentrations of Staphylococcus aureus, between 2 x 10(4) and 2 x 10(8) colony-forming units (CFU), were inoculated percutaneously at the implant site. MAIN OUTCOME MEASUREMENTS Implants, underlying bone, and surrounding soft tissues were removed under sterile conditions and quantitatively evaluated for bacterial growth. Infection was defined as positive bacterial growth at the bone-implant interface. RESULTS The overall infection rate was 45 percent. The infection dose of 50 percent (ID50) was 7.08 x 10(5) CFU for the DCP group and 8.51 x 10(6) CFU for the PC-Fix group. The infection rate was 63 percent (twelve of nineteen animals) for the DCP group and 26 percent (five of nineteen animals) for the PC-Fix group. This difference was statistically significant (p = 0.022). CONCLUSIONS After local bacterial challenge, we found a statistically significant difference in the infection rates depending on the implant design. The higher infection resistance associated with the PC-Fix design seems to be related to the reduced contact area at the bone-implant interface.

Prinzipien chirurgischer Therapiekonzepte der postoperativen und chronischen Osteomyelitis

ZusammenfassungDie postoperative Infektion des Knochens stellt sowohl in ihrer akuten als auch in der chronischen Verlaufsform eine der schwersten Komplikationen orthopädischer und unfallchirurgischer Operationen dar. Die Therapie beinhaltet nicht nur eine aufwendige bildgebende und mikrobiologische Diagnostik und aufwendige chirurgische Interventionen sondern auch eine intensive physikalische Therapie. Trotz des beträchtlichen Aufwands gelingt es nicht immer die Chronifizierung der Entzündung zu verhindern respektive eine definitive Infektsanierung zu gewährleisten. Zusätzlich sind die chronischen Knocheninfekte nahezu immer mit weiteren funktionellen Einschränkungen, wie limitierte Gelenkbeweglichkeit, neurologische Defizite und Schmerzen verbunden. Bei akuten postoperativen Infekten ist deshalb ein konsequentes chirurgisches Vorgehen besonders wichtig, um die Chronifizierung zu verhindern. Die Prinzipien bestehen in der Dekontamination durch Nekrosektomie und Spülung. Isolierte epifasziale Revisionen eines Operationsgebietes sind ebenso unzureichend, wie eine fehlende schichtübergreifende Wundrandexzision.Bei den chronischen Infekten muss zur definitiven Sanierung ein radikales Knochen- und Weichteildébridement erfolgen. Die Wiederherstellung des Weichteilmantels erfolgt entweder durch lokalen oder freien Gewebetransfer. Muskel(haut)lappenplastiken werden bevorzugt, da die Keimresistenz durch die „Luxusperfusion“ größer ist als bei fasziokutanen Transplantaten. Die knöcherne Rekonstruktion erfolgt durch Spongiosaplastik (partielle Defekte), Segmenttransport (Kontinuitätsdefekte) oder freie, gefäßgestielte Knochen(muskel)transplantation (große partielle Defekte).Die in der Regel für die Patienten sehr aufwendigen Rekonstruktionsmaßnahmen, müssen vor Therapiebeginn im Detail besprochen werden. Übersteigt das notwendige Resektionsausmaß die Rekonstruktionsmöglichkeiten, müssen die Therapiealternativen Wiederherstellung der Funktion bei persistierender Entzündung, symptomatische infektberuhigende Therapie und Amputation mit dem Patienten besprochen werden. Da jedes Therapiekonzept aus mehreren unverzichtbaren Pfeilern besteht, ist eine enge und gute Kommunikation und Kooperation zwischen Chirurgen, plastischen Chirurgen, Radiologen und Mikrobiologen eine Grundvoraussetzung.AbstractInfection of the bone is one of the most serious complications in the field of orthopedic and trauma orthopedic surgery. Sufficient treatment protocols not only contain complex surgical procedures but also sophisticated diagnostic tools, proper use of antibiotics, and intensive physical therapy right from the beginning. Even in light of these advanced treatment protocols, which have great impact on both patients and health care systems, persisting infection and residual functional deficits of the extremities are not rare. In cases of early (acute) infection, the main objective is to avoid chronification by diligent surgical interventions. The surgical principle is the meticulous debridement and lavage of the situs. Revision of only the epifascial layers is as inadequate as the simple reopening of the wound without excision of the whole wound including all tissue layers. In cases of chronic soft tissue and bone infection, radical debridement of all infected and scar tissue is also the basic requirement of treatment. Reconstruction of the soft tissue envelope is done by local or free flap surgery. Because of they are better resistant to infection, musculo(cutaneous)flaps are preferred. Bony reconstruction is done by autologous cancellous bone grafting (partial defects), segment transport (full thickness defects), or freely transplanted vascularized bone grafts (large partial defects).Both soft tissue and osseous reconstruction take a relatively long period of time requiring several operations and periods of hospitalization. These have to be discussed and explained to the patients extensively. If the required amount of resection and the capability of reconstruction do not coincide, the surgeon and the patient have to decide whether restoration of function without definitive infection care, symptomatic infection therapy, or amputation is the most proper treatment option according to the patient’s everyday needs and lifestyle. Because each treatment protocol is a composition of orthopedic trauma surgeons, plastic surgeons, radiologists, microbiologists, and physical therapists, reliable cooperation and communication is essential.

Influence of a standardized closed soft tissue trauma on resistance to local infection. An experimental study in rats.

Purpose: The etiology of local posttraumatic infection in the locomotor system depends on the amount, virulence and pathogenicity of the inoculated microorganisms and the local/systemic host damage due to the type and extent of the accident or iatrogenic trauma. The relative effect of these factors remains unclear. In particular, it is still unclear today whether—in presence of microorganisms—soft tissue damage and its pathophysiological consequences lead to infection after soft tissue trauma, or whether the bacterial contamination is the primarily cause for posttraumatic infection. The aim of the project was to gain information on the consequences of a soft tissue injury in terms of resistance to local infection. Since clinical populations are too heterogeneous, the problem was investigated in a standardized, reduced (no surgery or implants) experimental in vivo model.

Polylactide implants and bacterial contamination : An animal study

Although bioresorbable aliphatic polyesters derived from lactic acid are now used clinically as sutures, bone-fracture fixation devices and sustained-release drug-delivery systems, very little is known about their behavior in the infected environment. The aim of the present study was to compare the resistance to infection of two polylactide implants with different degradation characteristics, and to evaluate the influence of a bacterial challenge on their mechanical and physicochemical properties. Various quantities of a beta-haemolyzing strain of Staphylococus aureus (V 8189-94) were inoculated into the medullary cavity of rabbit tibiae, and an extruded polylactide rod composed of either P(L)LA (Poly(L-Lactide)) or P(L/DL)LA (Poly(L/DL-Lactide)) was then inserted. Animals were sacrificed four weeks after surgery. The tibiae and implants were removed under sterile conditions and evaluated microbiologically by culturing. The severity of infection was graded according to positive colony-forming units in the bone. The mechanical properties of the retrieved implants were assessed by 4-point bending and shear tests, performed in compliance with the ASTM D790 standard and their physicochemical characteristics also were characterized. P(L)LA and P(L/DL)LA implants were equally resistant to local infection, their mechanical and physicochemical properties being unaffected by bacterial challenge. Hence, once an infection has become established, the release of bactericidal/bacteriostatic by-products during implant degradation does not appear to affect its natural course. The release of bactericidal/bacteriostatic degradation products at the implantation site is unlikely to affect the natural course of an established infection.

Local application of basic fibroblast growth factor increases the risk of local infection after trauma: An in-vitro and in-vivo study in rats

Introduction Local application of growth factors to stimulate wound and fracture healing is attracting increasing interest. We studied the effect of local application of a potent angiogenic growth factor, basic fibroblast growth factor (bFGF), on resistance to local infection after soft tissue trauma. Methods For in-vitro and in-vivo experiments, we used recombinant human bFGF. The in-vitro investigations were performed by isolation of human leukocyte fractions, cytokine analysis, phagocytosis assay, flow cytometry, and LDH assay. For the in-vivo investigation, a paired comparison of infection rates was carried out on Sprague-Dawley rats after standardized, closed soft tissue trauma and local, percutaneous bacterial inoculation of different concentrations of Staphylococcus aureus (2 × 104 to 2 × 107 colony-forming units (cfu)). The lower leg was treated with 1, 10 or 100 ng bFGF (16 animals for each concentration) and without bFGF (16 animals). Results Cytotoxic reactions due to the concentrations of bFGF used could be excluded in the in-vitro tests since incubations of isolated peripheral blood mononuclear cells (PBMCs) with increasing concentrations of bFGF for 24 h did not lead to an increase in the release of lactate dehydrogenase in the culture supernatants compared to corresponding control incubations without any bFGF added. A significant increase in cytokine release was observed after the co-incubation of PBMCs with 100 or 200 ng of the same bFGF that was used for the animal experiments. Furthermore, the capacity of phagocytes in whole blood to phagocytose bacteria was suppressed in the presence of 100 ng exogenously added bFGF. We found continuously reduced granulocytic phagocytosis in FGF-supplemented blood compared to non-supplemented blood. In the in-vivo investigation, the infection rate for the group without bFGF was 0.25. In the groups with 1, 10 and 100 ng bFGF, the infection rates were 0.5, 0.7 and 0.8, respectively. A dose-dependent increase in infection rate was observed after local application of bFGF, compared to the untreated control group. The difference in infection rates for the groups in which 10 and 100 ng bFGF was used, relative to the group without bFGF, was statistically significant. Interpretation If these initial results are confirmed for other potent angiogenic growth factors, then the local use of growth factors for stimulation of wound and bone healing—a main focus of current research in traumatology—will have to be reconsidered and preceded with a strict evaluation of the risks and benefits.

Vorgeworfene Behandlungsfehler nach postoperativen Infekten am Bewegungsapparat Analyse von 261 gutachtlichen Bescheiden

Summary. Postoperative infection in the locomotor system may lead to malpractice suits. The aim of the study was to determine the success rate of these claims and the type of expert-confirmed medical negligence so that strategies for avoiding such negligence can be offered. A total of 261 decrees concerning suspected malpractice after postoperative infection in the locomotor system were retrospectively evaluated. Of these, 43.7 % claims were successful. The most frequent type of negligence was late diagnosis (34.2 %), followed by inconsistant treatment (27.2 %) and insufficient surgical revision (5.3 %). In 33.3 %, combined types of negligence were found. Most frequently, negligence was suspected after infection following hand surgery and internal fixation of long bones. The highest success rate of claims was seen after puncture of joints (69.2 %). Insufficient documentation was confirmed in 15.3 %. The majority of negligence resulted from diagnostic and therapeutic doubts, which could be avoided, e. g., by a clear definition of infection, consultation of a second opinion, a 2nd-look operation, undelayed and radical surgical revision, painstaking follow-up and disciplined documentation.Zusammenfassung. Postoperative Infekte am Bewegungsapparat können zum Vorwurf eines ärztlichen Behandlungsfehlers führen. Untersuchungsziel war, Anerkennungsrate und Art gutachtlich bestätigter Fehler festzustellen, um Vermeidungsstrategien anzubieten. 261 Bescheide zu vermuteten Behandlungsfehlern bei postoperativen Infekten am Bewegungsapparat wurden retrospektiv ausgewertet. Die Anerkennungsrate betrug 43,7 %. Häufigster Fehler war die verspätete Diagnose (34,2 %), gefolgt von inkonsequenter Therapie (27,2 %) und insuffizienter operativer Revision (5,3 %). In 33,3 % lagen Fehlerkombinationen vor. Die meisten Fehler wurden bei Infektionen nach Eingriffen an der Hand und Osteosynthesen großer Knochen vermutet. Die Anerkennungsrate war nach Gelenkpunktionen am höchsten (69,2 %). In 15,3 % wurden Dokumentationsmängel attestiert. Die Mehrzahl der Fehler resultierte aus diagnostischer und therapeutischer Unsicherheit, die z. B. durch eine klare Infektdefinition, Einholen einer zweiten Meinung, „Second-look-Operation“, unverzögerte und radikale Revisionseingriffe, sorgfältige Nachkontrolle und disziplinierte Dokumentation vermeidbar wären.

Pathophysiologie der posttraumatischen Osteitis

ZusammenfassungIn den letzten Jahrzehnten gelang es durch Etablierung neuer Operationstechniken und -taktiken, durch an das Infektionsrisiko adaptierte Indikationsstellungen, durch Chemotherapeutika und durch neue Implantatentwicklungen die posttraumatische Infektionsrate deutlich zu minimieren. Hierbei waren neue Erkenntnisse über die pathophysiologischen Mechanismen der posttraumatischen und postoperativen Osteitis wegweisend. Trotzdem ziehen posttraumatische Infektionen weiterhin oftmals erhebliche gesundheitliche und ökonomische Folgen nach sich.In diesem Artikel werden die wesentlichen pathophysiologischen Mechanismen der posttraumatischen Infektionsentstehung zusammengefasst. Es wird versucht, neue Denkanstöße zur posttraumatischen Osteitisprophylaxe und -therapie zu geben.AbstractOver the last few decades, significant reduction of post-traumatic infections could be attained by establishing novel surgical techniques and tactics, by adapting surgical decisions to the risk of infection, by employing chemotherapeutic agents, and by developing new implants. Here a novel understanding of the pathophysiologic mechanisms of post-traumatic and postoperative osteomyelitis were directive. Nevertheless, post-traumatic infections later cause significant physical and economic sequelae.This article sums up the fundamental pathophysiological mechanisms of post-traumatic infection. New ideas about post-traumatic prevention and therapy of osteomyelitis are discussed.