Sascha Goebel

FGF23 is a putative marker for bone healing and regeneration.

Besides numerous other factors, fibroblast growth factor receptor (FGFR) signaling is involved in fracture healing and bone remodeling. FGF23 is a phosphatonin produced by osteoblastic cells, which signals via FGFR1, thereby exerting effects in bone and kidney. We analyzed if serum FGF23 levels might be an indicator to predict fracture healing and union. FGF23 (C‐Term) was elevated on day 3 postoperatively in 55 patients sustaining an exchange of total hip implants due to aseptic loosening. A prospective study of 40 patients undergoing primary hip arthroplasty also showed elevated FGF23 (C‐Term) but no change in FGF23 (intact) levels on days 1, 4, and 10 postoperatively. Serum phosphate and phosphate clearance stayed within normal ranges. FGF23 mRNA expression in ovine callus was compared between a standard and delayed course of osteotomy healing. In the standard model, a marked increase in FGF23 mRNA expression compared to the delayed healing situation was observed. Immunohistochemical analysis showed FGF23 production of osteoblasts and granulation tissue in the fracture callus during bone healing. In conclusion, FGF23 is involved in bone healing, can be measured by a sensitive assay in peripheral blood, and is a promising candidate as an indicator for healing processes prone to reunion versus nonunion.

Synergistic effects of mixed TiAlV and polyethylene wear particles on TNFalpha response in THP-1 macrophages.

Abstract TNFα is a potent osteoclastogenic cytokine that has a fundamental role in the pathogenesis of wear particle-induced osteolysis. Wear particles of one composition and their biological effects are well characterised. In contrast, little is known about the effects of mixed particles with respect to mix ratio and particle concentration. We evaluated the effects of different mix ratios of polyethylene and TiAlV particles on TNFα response. We used a human monocytic cell line (THP-1) in this in vitro study. THP-1 monocytes were differentiated to macrophage-like cells and exposed to different mixtures of lipopolysaccharide-detoxified polyethylene and TiAlV particles. TNFα was analysed in culture supernatants using ELISAs. Both polyethylene and TiAlV particles induced a dose- and time-related release of TNFα, with maximum levels after 6 h. A PE/TiAlV mix ratio of 36:1 at 108 particles/ml induced significantly higher TNFα concentrations compared to equal particle concentrations of isolated TiAlV (p=0.047) or PE (p=0.044), indicating the synergistic effect of mixed particles. These results provide evidence that TiAlV and polyethylene particles have significant synergistic effects, depending on the mix ratio and particle concentrations. This supra-additive effect can contribute substantially to the pathogenesis of implant particle-induced osteolysis.TNFalpha is a potent osteoclastogenic cytokine that has a fundamental role in the pathogenesis of wear particle-induced osteolysis. Wear particles of one composition and their biological effects are well characterised. In contrast, little is known about the effects of mixed particles with respect to mix ratio and particle concentration. We evaluated the effects of different mix ratios of polyethylene and TiAlV particles on TNFalpha response. We used a human monocytic cell line (THP-1) in this in vitro study. THP-1 monocytes were differentiated to macrophage-like cells and exposed to different mixtures of lipopolysaccharide-detoxified polyethylene and TiAlV particles. TNFalpha was analysed in culture supernatants using ELISAs. Both polyethylene and TiAlV particles induced a dose- and time-related release of TNFalpha, with maximum levels after 6 h. A PE/TiAlV mix ratio of 36:1 at 10(8) particles/ml induced significantly higher TNFalpha concentrations compared to equal particle concentrations of isolated TiAlV (p=0.047) or PE (p=0.044), indicating the synergistic effect of mixed particles. These results provide evidence that TiAlV and polyethylene particles have significant synergistic effects, depending on the mix ratio and particle concentrations. This supra-additive effect can contribute substantially to the pathogenesis of implant particle-induced osteolysis.

Correlation Between Depressive Symptoms and Perioperative Pain A Prospective Cohort Study of Patients Undergoing Orthopedic Surgeries

Objectives:In previous research a close link between depression and postoperative pain has been described. However, the direction of impact remains unclear. The present longitudinal study aimed to clarify the prognostic value of depressive symptoms for perioperative pain and to explore the causal nature of the association between depressive symptoms and perioperative pain. Methods:In this prospective cohort study, 200 patients scheduled for orthopedic surgery were enrolled. They were evaluated preoperatively (T1) and on the second postoperative day (T2) and on the day of discharge (T3). Perioperative pain was monitored using a visual analogue scale-based pain assessment protocol, and depressive symptoms were measured with the self-reported Patient Health Questionnaire. Cross-lagged multiple regression analyses were performed without and with adjusting for possible confounders (sex, American Society of Anesthesiologists physical status, type of surgery, type of anesthesia). Results:We found significant and substantial links between depressive symptoms and perioperative pain, within a time point and across time intervals, showing consistency with a model of reciprocal impact of depressive symptoms and perioperative pain. No causal priority of one factor over the other was evident. However, after adjusting for possible confounders, only depressive symptoms in the early postoperative period (T2) remained predictive for pain at discharge (T3) and preoperative pain (T1) predicted postoperative depressive symptoms at both T2 and T3. Conclusions:Our results suggest that early postoperative depressive symptoms predicts pain at discharge and preoperative pain predicts postoperative depressive symptoms. In conclusion, perioperative pain therapy should include the treatment of both, pain and depressive symptoms, to achieve sufficient pain relief. The evidence regarding the causal relationships between depressive symptoms and perioperative pain, however, must be tested in future research.

Elevated postoperative pain levels following orthopedic surgery. Depression as a strong predictor

The aim of this study was to examine whether depression is a strong predictor of elevated postoperative pain levels following orthopedic surgery and whether the implementation of standardized pain management is more beneficial for patients with depression. We performed a non-randomized, prospective study with two different groups of patients who underwent orthopedic surgery. Group 1 (n=249) received non-standardized pain therapy whereas group 2 (n = 243) was treated with a standardized pain management concept. Effects of the treatment were monitored with a VAS-based pain assessment protocol. Depression was measured preoperatively with the self-reported Patient Health Questionnaire (PHQ-9). Patients with the probable diagnosis of a current episode of major depression showed significantly higher postoperative pain than patients without a depressive episode. On the other hand, patients with depression benefited from the implementation of standardized pain management. Our data suggest a predictive value of depression for severe postoperative pain. Patients with depression benefited from standardized postoperative pain therapy, but were still suffering from significantly higher postoperative pain.

Upregulation of LITAF mRNA expression upon exposure to TiAlV and polyethylene wear particles in THP-1 macrophages / Hochregulation der LITAF-mRNA Expression nach Exposition gegenüber TiAlV- und Polyethylen-Abriebpartikeln in THP-1 Makrophagen

Abstract Tumor necrosis factor α (TNFα) plays a fundamental role in the pathogenesis of wear particle-induced periprosthetic osteolysis. However, particle-induced mechanisms that control TNFα gene expression are not yet well characterized. LITAF [lipopolysaccharide (LPS)-induced TNFα factor] is a novel transcription factor that regulates expression of the TNFα gene, but nothing is known about its role in wear particle-induced osteolysis. We evaluated the effect of titanium aluminum vanadium (TiAlV) and polyethylene particles on mRNA expression of LITAF. A human monocytic leukemia cell line (THP-1) was used in this in vitro study. THP-1 monocytes were differentiated to macrophage-like cells and exposed to LPS-detoxified polyethylene particles and prosthesis-derived TiAlV particles. Supernatant was used for TNFα protein measurement and total RNA was extracted from cells. LITAF was analyzed at the mRNA level using semiquantitative RT-PCR. Both polyethylene and TiAlV particles induced significant upregulation of LITAF mRNA that was followed by a significant TNFα response. These effects were dependent on the particle dose. Low particle concentrations exhibited no significant effect on expression of TNFα and LITAF mRNA. In comparison to exposure to polyethylene and TiAlV particles, LPS stimulation exhibited similar upregulation of LITAF mRNA, but led to an overwhelming TNFα response. Our findings provide evidence that LITAF is implicated in the pathogenesis of wear particle-induced osteolysis. Zusammenfassung Tumor necrosis factor α (TNFα) spielt eine fundamentale Rolle in der Pathogenese der abriebpartikelinduzierten Osteolyse. Indes sind die partikelinduzierten Mechanismen, die die Genexpression von TNFα kontrollieren, bisher nicht gut charakterisiert. LITAF [lipopolysaccharide (LPS)-induced TNFα] ist ein kürzlich identifizierter Transkriptionsfaktor, der die TNFα-Genexpression reguliert, wobei aber nichts bekannt ist über dessen Rolle bei der partikelinduzierten Osteolyse. Unser Ziel war es, die Effekte von Titan-Aluminium-Vanadium- (TiAlV) und Polyethylen-Partikeln auf die mRNA-Expression von LITAF zu untersuchen. In dieser in vitro-Studie verwendeten wir eine humane, monozytäre Zelllinie (THP-1). Die Zellen wurden zu makrophagenähnlichen Zellen differenziert und LPS-detoxifizierten Polyethylen- und TiAlV-Partikeln ausgesetzt. Im Überstand wurde TNFα gemessen, zudem wurde die gesamte RNA aus den Zellen extrahiert. LITAF wurde auf mRNA-Ebene mittels semiquantitativer RT-PCR analysiert. Sowohl Polyethylen- als auch TiAlV-Partikel induzierten eine signifikante Hochregulation von LITAF-mRNA, die von einer signifikanten TNFα-Antwort zeitlich gefolgt war. Die Effekte waren abhängig von der Partikelkonzentration. Niedrige Partikelkonzentrationen zeigten keine signifikanten Effekte auf die Expression von TNFα und LITAF-mRNA. Im Vergleich zur Stimulation mit Polyethylen- und TiAlV-Partikeln bewirkte LPS eine ähnliche Hochregulation von LITAF-mRNA, aber eine überschießende TNFα-Antwort. Die Ergebnisse liefern Beweiskraft, dass LITAF substanziell bei der Pathogenese der abriebpartikelinduzierten Osteolyse beteiligt ist.

Calcinosis Universalis of the Elbow: A Rare Case with Classical Presentation

Juvenile Dermatomyositis (JDM) is a rare autoimmune disease in children and adolescents. In these patients calcinosis might be the most characteristic symptom. However there are only few reported cases of intramuscular calcinosis in Dermatomyositis. We report a case of calcinosis universalis (CU) of the elbow in JDM successfully treated with broaching. The patient, a 24-year-old woman, suffered from a long history of JDM. On examination she presented with a fistula lateral to the olecranon and pain of the right elbow joint. Plain X-rays displayed a diffuse pattern of multiple periarticular, subcutaneous, and intramuscular calcifications. The patient underwent surgery for histological and microbiological sampling as well as broaching. Intraoperatively sinus formation and subfascial hard calcium deposition were found. Due to the risk of collateral tissue damage, incomplete broaching was performed. A local infection with Staphylococcus was diagnosed and treated with antibiotics. On six-week and 30-month follow-up the patient was free of pain and had very good function. Calcifications on standard radiographs had almost resolved entirely. This case report gives a summary on calcinosis in Dermatomyositis and adds a new case of recalcitrant CU to the literature. Broaching surgery proved to be a reliable treatment option in symptomatic calcinosis.

Erhöhter postoperativer Schmerz nach orthopädischen Operationen

The aim of this study was to examine whether depression is a strong predictor of elevated postoperative pain levels following orthopedic surgery and whether the implementation of standardized pain management is more beneficial for patients with depression. We performed a non-randomized, prospective study with two different groups of patients who underwent orthopedic surgery. Group 1 (n=249) received non-standardized pain therapy whereas group 2 (n = 243) was treated with a standardized pain management concept. Effects of the treatment were monitored with a VAS-based pain assessment protocol. Depression was measured preoperatively with the self-reported Patient Health Questionnaire (PHQ-9). Patients with the probable diagnosis of a current episode of major depression showed significantly higher postoperative pain than patients without a depressive episode. On the other hand, patients with depression benefited from the implementation of standardized pain management. Our data suggest a predictive value of depression for severe postoperative pain. Patients with depression benefited from standardized postoperative pain therapy, but were still suffering from significantly higher postoperative pain.

Erhöhter postoperativer Schmerz nach orthopädischen Operationen@@@Elevated postoperative pain levels following orthopedic surgery: Depression als starker Prädiktor@@@Depression as a strong predictor

The aim of this study was to examine whether depression is a strong predictor of elevated postoperative pain levels following orthopedic surgery and whether the implementation of standardized pain management is more beneficial for patients with depression. We performed a non-randomized, prospective study with two different groups of patients who underwent orthopedic surgery. Group 1 (n=249) received non-standardized pain therapy whereas group 2 (n = 243) was treated with a standardized pain management concept. Effects of the treatment were monitored with a VAS-based pain assessment protocol. Depression was measured preoperatively with the self-reported Patient Health Questionnaire (PHQ-9). Patients with the probable diagnosis of a current episode of major depression showed significantly higher postoperative pain than patients without a depressive episode. On the other hand, patients with depression benefited from the implementation of standardized pain management. Our data suggest a predictive value of depression for severe postoperative pain. Patients with depression benefited from standardized postoperative pain therapy, but were still suffering from significantly higher postoperative pain.

Präoperative Planung und Vorbereitung

Die korperliche Untersuchung beinhaltet neben einer umfassenden Anamnese die sorgfaltige klinische Inspektion und funktionelle Untersuchung. Auser den Bewegungsumfangen der Gelenke der oberen Extremitaten in alle Richtungen und der Stabilitat des Schultergelenkes ist insbesondere der Status der Muskulatur zu beachten. Die Uberprufung der Neurologie und der Durchblutung der oberen Extremitat komplettieren die Befunderhebung.