Michael Diefenbeck

Outcome of allogeneic vascularized knee transplants

Transplantation of vascularized knee joints is a novel approach in Composite Tissue Allotransplantation (CTA). In 1996 our group started a clinical knee transplantation project and six transplantations have been performed since. Key problems identified early were the monitoring of acute rejection and choice of an immunosuppressive regime. One graft was lost due to postoperative infection and one due to of noncompliance where the patient discontinued the immunosuppressant regime. In three cases late rejection lead to necrosis and graft dysfunction after 15, 16 and 24 months, respectively. Exit‐strategies were arthrodesis in one patient and Above Knee Amputation in two cases. With retrospective analysis after initial five cases the treatment protocol was improved. The immunosuppressive drug regime was altered, femoral diaphysis and knee joint grafting was combined and a vascularized block of donor skin and subcutaneous tissue was harvested with the graft (sentinel skin graft). The sentinel skin graft enabled us to monitor acute rejection by clinical and histological examination and avoid late rejection by rapid treatment with high dose steroids. In summary, over a four‐year period, one of six allogeneic vascularized knee transplants has survived, one was lost from a surgical site infection, one by noncompliance and three by late rejection. Analysis of our data leads us to suggest that knee transplantation should be limited to a combined injury consisting of extensive loss of cartilage and bone, deficient extensor mechanism and soft tissue and skin defects without any signs of infection. Transplantation should only be taken into consideration as last option before Above Knee Amputation in an otherwise healthy patient under 35 years of age.

Allograft vasculopathy after allogeneic vascularized knee transplantation

Composite tissue allotransplantation represents a new discipline in reconstructive surgery. Over the past 10 years, we have performed six human vascularized allogeneic knee transplantations. All of these grafts have been lost within the first 56 months. A histomorphologic assessment of the latest case resulted in the detection of diffuse concentric fibrous intimal thickening and occlusion of graft vessels. Findings are comparable with cardiac allograft vasculopathy. The lack of adequate tools for monitoring graft rejection might have allowed multiple untreated episodes of acute rejection, triggering myointimal proliferation and occlusion of graft vessels. Graft vasculopathy represents an obstacle to long‐term vascularized bone and joint allograft survival, and adequate tools for monitoring need to be developed.

Management of acute rejection 2 years after allogeneic vascularized knee joint transplantation.

Allotransplantation of vascularized knee joints is a novel approach in orthopaedic surgery. It was invented for patients suffering from the total loss of a knee joint including the extensor apparatus (patella, patella ligament, quadriceps tendon), caused by major trauma or post-traumatic infection [1]. Since 1994 grafting of three femoral diaphyses and five knee joints have been reported by our group [2,3]. In the follow up of the patients the main complication was late allograft rejection, which unfortunately led to above knee amputation in three cases. The key problem was how to monitor rejection crisis. Different to the hand transplantations, underwent by Dubernard et al. [4] and Jones et al. [5], the rejection status of the grafted knee cannot be observed by watching the skin colour or by taking skin biopsies. Because of this limitation, only indirect diagnostics like nuclear scintigraphy and single photon emission computerized tomography (SPECT) were available to gain information about the microcirculation of the graft [6]. In April 2002, we performed the sixth vascularized knee joint transplantation with an improved treatment protocol at the Berufsgenossenschaftliche Unfallklinik Murnau, Germany. The surgical technique remained unchanged, as published earlier [1,3]. As a new method to monitor early signs of graft rejection a block of donor skin and subcutaneous tissue with vascular pedicle was transplanted with the graft and inserted into the skin of the recipient (sentinel skin graft). A similar technique had previously been published by Lanzetta et al. in their hand transplantation project, where an additional full-thickness skin was transplanted onto the left hip area [7]. This skin served as a source of biopsies and as an additional area to monitor rejection, hence called ‘distant sentinel skin graft’ [7]. Immunosuppression was started immediately after reperfusion with a quadruple induction therapy for the first 7 days: antithymocyte globulin (ATG; 4 mg/kg BW i.v.), methylprednisolone (250 mg i.v.), FK 506 (tacrolimus; Prograf (Astellas GmbH (former Fujisawa), Munich, Germany), 10 mg p.o.) and mycophenolate mofetil (MMF; Cellcept (Roche Registration Limited, UK), 2 g). From the beginning of the second week immunosuppression was reduced to an oral triple therapy with FK 506, MMF and methylprednisolone (10 mg p.o.). The patient was discared 8 weeks after surgery, half weight-bearing and returned to his previous job after 6 months. About 1.5 years after transplantation the clinical follow up showed a good range of motion and a completely integrated sentinel skin graft (Fig. 1a and b).

Results of the T2 humeral nailing system with special focus on compression interlocking

BACKGROUND The outcome of interlocking nailing of humeral shaft fractures is controversial. Variations in implants, operative technique and follow-up parameters hinder comparative studies. The aim of this investigation was to evaluate the T2 humeral nailing system according to clinical results, and to recognise advantages and disadvantages of compression interlocking. METHODS A total of 36 consecutive humeral shaft fractures were treated with an interlocking humeral nail. In 23 cases the antegrade and in 14 cases the retrograde approach was used. Compression locking was performed in 21 and static locking in 15 cases. RESULTS At 22-month follow-up, bone consolidation was present in 35 cases; in 5 cases complications developed. There was no significant difference between compression and static locking nor between the antegrade and retrograde approach regarding complications, Constant shoulder score, mean Morrey elbow score, SF-12 physical score or SF-12 mental score. CONCLUSION Antegrade and retrograde interlocking nailing of humeral shaft fractures with the T2 nailing system can result in good functional outcome and unimpaired quality of life. Compression interlocking can minimise the fracture gap and increase the biomechanical stiffness. Potential disadvantages of compression interlocking include possible bending or loosening of the locking screw in the dynamic oblong hole. An additional static locking screw should be used on the humerus after compression interlocking.

Behandlungsstrategie beim Frühinfekt nach operativer Frakturversorgung

ZusammenfassungDer Frühinfekt nach operativer Frakturversorgung ist weiterhin eine gefürchtete Komplikation. Er bedeutet für den betroffenen Patienten eine gravierende Belastung und stellt für den behandelnden Chirurgen eine große Herausforderung dar.Um den Übergang eines Frühinfekts in eine chronische Osteitis zu verhindern, muss die adäquate Diagnostik rasch durchgeführt und die operative Revision dringlich geplant werden.Im Folgenden wird ein Revisionskonzept dargestellt, bei dem die Infektsanierung zunächst unter Erhaltung der Osteosynthese angestrebt wird.Kann jedoch nach 4 Revisionen die Keimfreiheit nicht erzielt werden, erfolgt die Entfernung des Osteosynthesematerials. Durch die Anwendung dieses Revisionsprotokolls konnte im eigenen Krankengut der Übergang in einen chronischen Krankheitsverlauf bisher verhindert werden.AbstractEarly infection following surgical treatment of a fracture remains a dreaded complication. It represents a serious burden for the afflicted patient and confronts the attending surgeon with a great challenge.To prevent an early infection from developing into chronic osteitis,adequate diagnostic measures must be promptly implemented and revision surgery planned with urgency.The following presents a concept for revision in which the goal is to eradicate the infection while retaining the osteosynthesis. If,however, asepsis can not be achieved after four revisions, the osteosynthesis material has to be removed. Up to now,we have been able to prevent a chronic clinical course using this protocol for revision.

Freezing of rat tibiae at -20°c does not affect the mechanical properties of intramedullary bone/implant-interface: brief report.

Background: The effects of freezing-thawing cycles on intramedullary bone-implant interfaces have been studied in a rat model in mechanical pull-out tests. Implants: Twenty TiAl6V4 rods (Ø 0.8 mm, length 10 mm) implanted in rat tibiae Methods: 10 rats underwent bilateral tibial implantation of titanium rods. At eight weeks, the animals were sacrificed and tibiae harvested for biomechanical testing. Eight tibiae were frozen and stored at -20°C for 14 days, the remaining eight were evaluated immediately post-harvest. Pull-out tests were used to determine maximum force and interfacial shear strength. Results: There were no significant differences between fresh and those of the frozen-thawed group in maximum force or in interfacial shear strength. Conclusion: Frozen Storage of rat tibiae containing implants at -20° C has no effects on the biomechanical properties of Bone/ Implant interface.

Knochenersatz durch Kallusdistraktion an der unteren Extremität

ZusammenfassungDie erfolgreiche Behandlung einer posttraumatischen chronischen Osteitis an der unteren Extremität gelingt oftmals nur um den Preis eines mehr oder weniger ausgedehnten Knochenverlusts. Zur Wiederherstellung langstreckiger knöcherner Substanzdefekte haben sich in den vergangenen Jahren verschiedene Verfahren des Segmenttransports, basierend auf der Ilizarov-Kallusdistraktion, etabliert. Für die technische Umsetzung eines solchen Segmenttransports stehen gleichermaßen extra- und intramedulläre Verfahren zur Verfügung. Die Indikationsstellung für einen Segmenttransport über Ringfixateur, monolateralen Fixateur externe oder intramedullären Kraftträger in Kombination mit Fixateur externe oder Seilzug als Transportsystem muss individuell unter Berücksichtigung verschiedener Faktoren entschieden werden. Dabei spielen Dauer und Ausdehnung der vorbestehenden Osteitis, zeitlicher Aufwand zur erfolgreichen Behandlung der Infektion, Weichgewebesituation, resultierende Länge der Defektstrecke nach Resektion sowie Alter, Risikofaktoren und Komorbidität des Patienten eine Rolle. Im folgenden Beitrag soll aus einer langjährigen klinischen Erfahrung in der Behandlung von postinfektiösen Defektzuständen an der unteren Extremität ein Algorithmus zum differenzierten Einsatz der verschiedenen Segmenttransporttechniken diskutiert werden.AbstractSuccessful treatment of posttraumatic chronic osteitis is often only achieved at the cost of some degree of bone loss. Various procedures for segmental transfer based on Ilizarov’s callus distraction technique have become established for reconstruction of extensive bony substance defects in recent years. Technically, both extramedullary and intramedullary procedures are available for the achievement of such a segmental transfer. Various factors must be taken into account when it is necessary to decide whether segmental transfer by means of a ring fixator, a unilateral fixateur externe or an intramedullary force carrier in combination with a fixateur externe or tension wires as the transfer system is indicated. These include how long the history of osteitis already is, how extensive it is, time taken for successful treatment of infection, soft tissue situation, resulting length of the defect following resection, and the patient’s age, together whether there are any patient-specific risk factors or comorbidities. In this paper an algorithm for deciding on the specific situations in which the different techniques of segmental transfer are indicated is discussed on the basis of many years of clinical experience in postinfectious defects on the lower extremities.

Multiresistente Erreger im Krankenhaus

ZusammenfassungMultiresistente Erreger (MRE) sind Krankeitserreger, die aufgrund ihrer Resistenz nur noch sehr eingeschränkt antibiotisch behandelt werden können. Für das Hygienemanagement im Krankenhaus steht weiterhin der methicillinresistente Staphylococcus aureus (MRSA) im Vordergrund. Seine aktuelle Prävalenz beträgt in Deutschland 21%. In Kombination mit der zunehmenden MRSA-Zirkulation zwischen verschiedenen Einrichtungen des Gesundheitssystems, der erschwerten effektiven Therapie von manifesten MRSA-Infektionen und knapper werdenden Ressourcen im Gesundheitssystem stellt dies eine kritische Situation dar. Nachdem in den letzten Jahren die Risikofaktoren für die MRSA-Besiedelung und -Übertragung erkannt worden sind, muss nun ein effektives MRSA-Management zur Bekämpfung und Eindämmung der resistenten Erreger eingesetzt werden. Eckpunkte dieser Surveillancemaßnahmen sind: primäres MRSA-Screening, krankenhaushygienische Maßnahmen, konsequente chirurgische Sanierung von Infektionen, Information der Betroffenen, ihrer Angehörigen und weiterbehandelnden Einrichtungen sowie Fort- und Weiterbildung aller an der Versorgung beteiligten Berufsgruppen.AbstractInfections caused by multiresistant pathogens can be treated only with a limited number of antibiotics. Methicillin-resistant Staphylococcus aureus (MRSA) remains the most important resistant bacterium in the context of hospital surveillance and prevention of nosocomial infections. The prevalence of MRSA is currently 21% in Germany. In combination with the cycle of MRSA transmission among various healthcare facilities, difficulties in effectively treating MRSA, surgical site infections, and the growing shortage of resources in the healthcare system, this is becoming a more and more critical situation. Risk factors for MRSA colonisation and transmission have been described in previous years, and an effective MRSA management program is now needed to control further increase in MRSA infections. This involves selective screening for MRSA, strict hospital hygiene, effective surgical treatment of infections, and education of patients, relatives, and all hospital staff.

Einsatz von Bone-morphogenetic Protein-7 (BMP-7) in der Behandlung von Pseudarthrosen der oberen und unteren Extremität

Zusammenfassung„Bone-morphogenetic Proteins“ (BMP) sind Knochenwachstumsfaktoren, die osteoinduktiv wirken. Seit 1992 kann BMP-7 als rekombinantes humanes (rh) Protein gentechnisch hergestellt werden. Nachdem tierexperimentelle und klinische Studien gezeigt hatten, dass rhBMP-7 die Neubildung von Knochen in ossären Defekten und Pseudarthrosen induziert, ist es seit 2001 in Europa zugelassen. Die Osteoinduktion ist in etwa so effektiv wie eine autologe Spongiosaplastik, jedoch ohne die Problematik der Spongiosaentnahmemorbidität.AbstractBone morphogenetic proteins (BMPs) are bone growth factors, which regulate bone formation during fetal development and bone repair after injury in postfetal life. Since 1992 BMP-7 has been produced by recombinant technique (rhBMP-7). Numerous animal models and clinical trials have shown that rhBMP-7 can induce de novo bone formation in segmental defects of bones and in cases of nonunion. Since 2001 rhBMP-7 has been approved for treatment of tibial nonunion in Europe. The effect of rhBMP-7 is comparable to the clinical and radiological results achieved with bone autografts. The problem of donor site morbidity (which occurs in up to 20% of all cases) is eliminated by the use of BMP-7. Long-term results and experience in clinical practice are not yet available.

Postembedding Decalcification of Mineralized Tissue Sections Preserves the Integrity of Implanted Biomaterials and Minimizes Number of Experimental Animals

Bone histology of decalcified or undecalcified samples depends on the investigation. However, in research each method provides different information to answer the scientific question. Decalcification is the first step after sample fixation and governs what analysis is later feasible on the sections. Besides, decalcification is favored for immunostaining and in situ hybridization. Otherwise, sample decalcification can be damaging to bone biomaterials implants that contains calcium or strontium. On the other hand, after decalcification mineralization cannot be assessed using histology or imaging mass spectrometry. The current study provides a solution to the hardship caused by material presence within the bone tissue. The protocol presents a possibility of gaining sequential and alternating decalcified and undecalcified sections from the same bone sample. In this manner, investigations using histology, protein signaling, in situ hybridization, and mass spectrometry on the same sample can better answer the intended research question. Indeed, decalcification of sections and grindings resulted in well-preserved sample and biomaterials integrity. Immunostaining was comparable to that of classically decalcified samples. The study offers a novel approach that incites correlative analysis on the same sample and reduces the number of processed samples whether clinical biopsies or experimental animals.