Kathi Thiele

Blood-borne human plasma cells in steady state are derived from mucosal immune responses

Providing humoral immunity, antibody-secreting plasma cells and their immediate precursors, the plasmablasts, are generated in systemic and mucosal immune reactions. Despite their key role in maintaining immunity and immunopathology, little is known about their homeostasis. Here we show that plasmablasts and plasma cells are always detectable in human blood at low frequency in any unimmunized donor. In this steady state, 80% of plasmablasts and plasma cells express immunoglobulin A (IgA). Expression of a functional mucosal chemokine receptor, C-C motif receptor 10 (CCR10) and the adhesion molecule beta(7) integrin suggests that these cells come from mucosal immune reactions and can return to mucosal tissue. These blood-borne, CCR10(+) plasmablasts also are attracted by CXCL12. Approximately 40% of plasma cells in human bone marrow are IgA(+), nonmigratory, and express beta(7) integrin and CCR10, suggesting a substantial contribution of mucosal plasma cells to bone marrow resident, long-lived plasma cells. Six to 8 days after parenteral tetanus/diphtheria vaccination, intracellular IgG(+) cells appear in blood, both CD62L(+), beta(7) integrin(-), dividing, vaccine-specific, migratory plasmablasts and nondividing, nonmigratory, CD62L(-) plasma cells of different specificities. Systemic vaccination does not impact on peripheral IgA(+) plasmablast numbers, indicating that mucosal and systemic humoral immune responses are regulated independent of each other.

HLA-DRhigh/CD27high plasmablasts indicate active disease in patients with systemic lupus erythematosus

Objectives: Monitoring of peripheral B-cell subsets in patients with systemic lupus erythematosus (SLE) revealed an activity-related expansion of CD27++CD20−CD19dim Ig-secreting cells. A similar subset has also been identified 6–8 days after tetanus/diphtheria vaccination in normal individuals and in patients with infectious disease. Methods: This subset was analysed further focussing on the HLA-DR surface expression in a cohort of 25 patients with SLE. Results: This study revealed that 86% (range 59–97%) of CD27++CD20−CD19dim cells express high levels of HLA-DR, are also expanded in the bone marrow, and represent plasmablasts enriched with anti-dsDNA secreting cells. The remaining CD27++CD20−CD19dim cells were HLA-DRlow and represent mature plasma cells. Importantly, HLA-DRhigh plasmablasts showed a closer correlation with lupus activity and anti-dsDNA levels than the previously identified CD27++CD20−CD19dim cells. Conclusion: HLA-DRhighCD27++CD20−CD19dim plasmablasts represent a more precise indicator of lupus activity and suggest that there is an overproduction or lack of negative selection of these cells in SLE.

Standardized immune monitoring for the prediction of infections after cardiopulmonary bypass surgery in risk patients

Infections are the most common cause of late complications in cardiopulmonary bypass (CPB) surgery patients, and are difficult to predict. Here we studied the diagnostic value of a standardized immune monitoring program based on recent advances in flow cytometry (exact quantification of surface‐marker expression) and cytokine determination (semiautomatic systems).

Current Failure Mechanisms After Knee Arthroplasty Have Changed: Polyethylene Wear Is Less Common in Revision Surgery

BACKGROUND The present study was designed to clarify which underlying indications can be currently considered the main reasons for failure after total knee arthroplasty as a function of time. METHODS We conducted a retrospective study that included all first revisions of total knee replacements during 2005 to 2010 at two high-volume arthroplasty centers. A revision was defined as the replacement of at least one prosthetic component. In the descriptive analysis, polyethylene wear, aseptic loosening, periprosthetic infection, malalignment, instability, arthrofibrosis, extensor mechanism deficiency, periprosthetic fracture, and retropatellar arthritis were given as the failure mechanism associated with an early, intermediate, or late time interval (less than one year, one to three years, and more than three years, respectively) after the index total knee arthroplasty. RESULTS Three hundred and fifty-eight revision total knee arthroplasties were included. Of those revisions, 19.8% were performed within the first year after the index arthroplasty. The most common indications for revision, besides aseptic loosening (21.8%), were instability (21.8%), malalignment (20.7%), and periprosthetic infection (14.5%). Revisions due to polyethylene wear (7%) rarely occurred. In the early failure group, the primary causes of revision were periprosthetic infection (26.8%) and instability (23.9%). In the intermediate group, instability (23.3%) and malalignment (29.4%) required revision surgery, whereas late failure mechanisms were aseptic loosening (34.7%), instability (18.5%), and polyethylene wear (18.5%). CONCLUSIONS Aseptic loosening, instability, malalignment, and periprosthetic infection continue to be the primary failure mechanisms leading to revision surgery. Contrary to previous literature, the results in the present study showed a substantial reduction in implant-associated revisions such as those due to polyethylene wear. Failure mechanisms that occur persistently early and in the intermediate term, such as periprosthetic infection, instability, and malalignment, remain common causes of revision surgery. LEVEL OF EVIDENCE Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Toxicity of antiseptics against chondrocytes: What is best for the cartilage in septic joint surgery?

In septic joint surgery, the most frequently used antiseptics are polyhexanide, hydrogen peroxide and taurolidine. The aim of this study was to examine the effects of these antiseptics on viability of human chondrocytes. Our hypothesis was that antiseptics and supplemental irrigation with sodium chloride lavage are less toxic on human chondrocytes than treatment with antiseptics only. Primary human chondrocytes were isolated and cultured from six donated human knee joints. Polyhexanide, hydrogen peroxide or taurolidine were added to the cultures. Toxicity analysis was performed by visualisation of cell structure using light microscopy and LDH activity. The determination of vital cells and total cell numbers of chondrocytes treated with antiseptics partly followed by irrigation with sodium chloride solution was performed by using Casy Cell-Counter. Light microscopic data revealed a defect in cell structure after addition of antiseptics. We showed a significant increase of LDH enzyme activity after the treatment with polyhexanide or taurolidine. After treatment with antiseptics followed by sodium chloride solution a significant increase of vital and total cell numbers resulted in comparison with the chondrocytes that were only treated with antiseptics. The data show that treatment with polyhexanid, hydrogen peroxide or taurolidine induces cell death of human chondroctes in vitro. The application of sodium chloride solution after the treatment with polyhexanide and hydrogen peroxide possibly has a protective effect on chondrocyte viability.

Nachwuchsmangel in der Unfallchirurgie und Orthopädie

ZusammenfassungDie Gründe des Nachwuchsmangels in chirurgischen Disziplinen sind vielfältig diskutiert worden. Als Ursachen des Attraktivitätsverlusts werden exemplarisch eine arztfremde progrediente Arbeitsbelastung, ungünstige Arbeitszeiten und unzureichender Ausgleich für Bereitschaftsdienste erwähnt. Auch eine zunehmende Feminisierung des ärztlichen Berufs mit Abkehr vom chirurgischen Fach bei Unvereinbarkeit von familiärer Planung und den Ansprüchen der chirurgischen Weiterbildung wird häufig genannt. Umfragen, die Wahl des Facharztes thematisierend, bezeugen einen großen Einfluss auf die Sicht für die eigene Zukunft als Ärztin oder Arzt durch die individuellen Erfahrungen der Befragten im Verlauf ihres Studiums. Um dennoch die Attraktivität und Vielfältigkeit unserer Fachdisziplin zu verdeutlichen, initiierte man Programme für Studenten durch die Leiter der Konvente der Hochschullehrer für Orthopädie und Unfallchirurgie und dem Geschäftsführenden Vorstand der DGOU, die großen Anklang fanden. Um dem enormen Zuspruch gerecht zu werden, bat man um Unterstützung an weiteren Universitäten. Infolge dessen fand am 16.02.2010 der „Unfallchirurgische und Orthopädische Tag für Studenten“ an der Charité Berlin statt. Ziel dieses Tages war, die fehlende Präsenz praktischer Ausbildungsinhalte im regulären Studiengang zu minimieren und inhaltliche Anregungen für die Wahl dieses Facharztes zu geben.AbstractThe reasons for a shortage of young people in trauma surgery and orthopedics have often been discussed. Atypical progression of medical operating levels, antisocial working hours and an inadequate financial compensation for on-call duties have been given as the reasons for a lack of interest in the discipline. Additionally a progressive feminization of the medical profession and rejection of surgical disciplines because of a mismatch with family interests and the demands of advanced surgical training have also been named. Surveys on the choice of medical specialization reveal that experiences during the course of studying have a great influence on future prospects and are immensely important for the further focusing on the future as a medical doctor. In order to increase the attractiveness of the specialization, programs for students were initiated by the heads of the Conventions of Higher Education Lecturers for Orthopedics and Trauma Surgery and the management of the German Society for Orthopedics and Trauma Surgery. Due to the enormous popularity auxiliary projects were demanded. Consequently a “Trauma Surgery and Orthopedic Day for Students” was organized on 16th February 2010 in the Musculoskeletal Centre of the Charité in Berlin. The aim was to convey practical skills and to inspire the choice of this specialization in the future.

Epicondylopathia humeri radialis et ulnaris

ZusammenfassungDie Epicondylopathia humeri radialis und ulnaris ist eine schmerzhafte Erkrankung des Sehnenansatzgewebes der Extensoren- bzw. Flexorengruppe, die ätiologisch auf eine sportliche oder berufliche Überlastung der Handgelenkextensoren bzw. -flexoren zurückzuführen ist. Pathomorphologisch imponiert ein ödematös verändertes Gewebe im Bereich des M. extensor carpi radialis brevis, der zudem partiell oder komplett rupturiert sein kann. Nichtoperative Verfahren stellen noch immer den therapeutischen Kernbereich der Epikondylopathien dar. Neuere Verfahren wie die Injektion von Botulinumtoxin (hohe Evidenz), Applikation von „platelet-rich plasma“ (mäßige Evidenz) und die extrakorporale Stoßwellentherapie (geringe Evidenz) sind mit unterschiedlichem klinischem Erfolg in die therapeutischen Algorithmen aufgenommen worden. Bestehende chirurgische Verfahren werden erst nach Ausschöpfung der konservativen Therapieverfahren empfohlen. Im Zuge der Entwicklungen arthroskopischer Techniken hat sich die Ellenbogengelenkarthroskopie etabliert, da sie die simultane Diagnostik und ggf. auch Therapie intraartikulärer Begleitpathologien ermöglicht.AbstractTennis or golfer elbow (epicondylopathia humeri radialis et ulnaris) are painful disorders of the tendon insertion tissues of the extensor or flexor groups that can be attributed to an overload due to sports or labour activity of the wrist extensor or flexor muscles. Pathomorphologically the tendon of the musculus extensor carpi radialis brevis is characterized by edematous changes and even partial or complete ruptures. Non-surgical procedures are still the therapeutic mainstay for all forms of epicondylitis. Recently presented methods such as the injection of botulinum toxin (good evidence), administration of platelet-rich plasma (moderate level of evidence) and the extracorporal shock wave therapy (low level of evidence) have been included in the therapeutic algorithms with varying degrees of clinical success. Established surgical procedures are recommended after failed conservative treatment. Operative techniques have been expanded to arthroscopic techniques with the advantage of improved diagnostics and therapy of intraarticular pathologies.

Influence of the Position of the Fibular Head After Implantation of a Total Knee Prosthesis on Femorotibial Rotation

A gold standard for the correct rotation of the tibial component has not been established in total knee arthroplasty (TKA). The target parameter of correct rotation is the facilitation of femorotibial rotation over the entire range of motion with no implant overhang. Although the origin of the lateral collateral ligament is a recognized landmark for determining the rotation of the femoral component (epicondylar axis), the attachment of the lateral collateral ligament has not been taken into consideration for adjusting tibial rotation until now. The objective of the current investigation was to examine whether the position of the fibular head, as the attachment of the lateral collateral ligament, influences femorotibial rotation. Seventy patients who underwent TKA were enrolled in this retrospective study. Computed tomography (CT) of the operated knee was performed 6 months postoperatively in all cases and the position of the lateral facet of the fibular head and the tibial tuberosity, and the geometric center of the tibia and the femoral epicondyles were determined. The angle between the lateral facet of the fibular head, the geometric center of the tibia, and the tibial tuberosity was 45.7°±6.9°. The angle between the surgical epicondylar axis and the line from tibial tuberosity to tibial center was 69°±8.3°. This close correlation (R=.73; P<.001) shows that the position of the fibular head determines femorotibial rotation. The fibular head may become a helpful landmark for establishing the rotation of the tibial component; it could be useful in interpretation of postoperative CT scans in knees suspected of tibial malrotation.

[Distal biceps tendon rupture : Overview and own procedure].

Mainly males in their 40s and 50s suffer from distal biceps tendon rupture. The diagnosis is made by clinical evaluation and is usually confirmed by magnetic resonance imaging. Different approaches and reconstruction techniques have been described in the past, and the clinical results are mostly good and excellent. Thereby the decision regarding which technique to use lies with the surgeon. However, specific complications have been described and should be considered.

Lack of new trainees in trauma surgery and orthopedics. An approach to a solution

ZusammenfassungDie Gründe des Nachwuchsmangels in chirurgischen Disziplinen sind vielfältig diskutiert worden. Als Ursachen des Attraktivitätsverlusts werden exemplarisch eine arztfremde progrediente Arbeitsbelastung, ungünstige Arbeitszeiten und unzureichender Ausgleich für Bereitschaftsdienste erwähnt. Auch eine zunehmende Feminisierung des ärztlichen Berufs mit Abkehr vom chirurgischen Fach bei Unvereinbarkeit von familiärer Planung und den Ansprüchen der chirurgischen Weiterbildung wird häufig genannt. Umfragen, die Wahl des Facharztes thematisierend, bezeugen einen großen Einfluss auf die Sicht für die eigene Zukunft als Ärztin oder Arzt durch die individuellen Erfahrungen der Befragten im Verlauf ihres Studiums. Um dennoch die Attraktivität und Vielfältigkeit unserer Fachdisziplin zu verdeutlichen, initiierte man Programme für Studenten durch die Leiter der Konvente der Hochschullehrer für Orthopädie und Unfallchirurgie und dem Geschäftsführenden Vorstand der DGOU, die großen Anklang fanden. Um dem enormen Zuspruch gerecht zu werden, bat man um Unterstützung an weiteren Universitäten. Infolge dessen fand am 16.02.2010 der „Unfallchirurgische und Orthopädische Tag für Studenten“ an der Charité Berlin statt. Ziel dieses Tages war, die fehlende Präsenz praktischer Ausbildungsinhalte im regulären Studiengang zu minimieren und inhaltliche Anregungen für die Wahl dieses Facharztes zu geben.AbstractThe reasons for a shortage of young people in trauma surgery and orthopedics have often been discussed. Atypical progression of medical operating levels, antisocial working hours and an inadequate financial compensation for on-call duties have been given as the reasons for a lack of interest in the discipline. Additionally a progressive feminization of the medical profession and rejection of surgical disciplines because of a mismatch with family interests and the demands of advanced surgical training have also been named. Surveys on the choice of medical specialization reveal that experiences during the course of studying have a great influence on future prospects and are immensely important for the further focusing on the future as a medical doctor. In order to increase the attractiveness of the specialization, programs for students were initiated by the heads of the Conventions of Higher Education Lecturers for Orthopedics and Trauma Surgery and the management of the German Society for Orthopedics and Trauma Surgery. Due to the enormous popularity auxiliary projects were demanded. Consequently a “Trauma Surgery and Orthopedic Day for Students” was organized on 16th February 2010 in the Musculoskeletal Centre of the Charité in Berlin. The aim was to convey practical skills and to inspire the choice of this specialization in the future.