Gerhard M. Hobusch

Human osteoarthritic knee cartilage: fingerprinting of adhesion/growth‑regulatory galectins in vitro and in situ indicates differential upregulation in severe degeneration

The apparent connection of galectin-3 to chondrocyte survival and osteoarthritis-like cartilage modifications in animal models provided incentive for the mapping of seven members of this family of adhesion/growth-regulatory proteins in human cartilage specimens. Starting with work in vitro, RT-qPCR analyses and immunocytochemistry revealed gene transcription and protein presence in cultured OA chondrocytes, especially for galectin-1, galectin-3 and galectin-8. Immunohistochemistry in clinical specimens with mild and severe cartilage degeneration detected galectins in chondrocytes—with upregulation, especially of galectin-1 in areas of severe degeneration—accompanied by α2,6-sialylation in the pericellular matrix. Given the possibility for additive/antagonistic activities between galectins, these results direct further research toward examining cellular effects of (1) these proteins (alone or in combination) on chondrocytes and (2) remodeling of the chondrocyte glycophenotype.

Vascularised or non-vascularised autologous fibular grafting for the reconstruction of a diaphyseal bone defect after resection of a musculoskeletal tumour

Resection of a primary sarcoma of the diaphysis of a long bone creates a large defect. The biological options for reconstruction include the use of a vascularised and non-vascularised fibular autograft. The purpose of the present study was to compare these methods of reconstruction. Between 1985 and 2007, 53 patients (26 male and 27 female) underwent biological reconstruction of a diaphyseal defect after resection of a primary sarcoma. Their mean age was 20.7 years (3.6 to 62.4). Of these, 26 (49 %) had a vascularised and 27 (51 %) a non-vascularised fibular autograft. Either method could have been used for any patient in the study. The mean follow-up was 52 months (12 to 259). Oncological, surgical and functional outcome were evaluated. Kaplan-Meier analysis was performed for graft survival with major complication as the end point. At final follow-up, eight patients had died of disease. Primary union was achieved in 40 patients (75%); 22 (42%) with a vascularised fibular autograft and 18 (34%) a non-vascularised (p = 0.167). A total of 32 patients (60%) required revision surgery. Kaplan-Meier analysis revealed a mean survival without complication of 36 months (0.06 to 107.3, sd 9) for the vascularised group and 88 months (0.33 to 163.9, sd 16) for the non-vascularised group (p = 0.035). Both groups seem to be reliable biological methods of reconstructing a diaphyseal bone defect. Vascularised autografts require more revisions mainly due to problems with wound healing in distal sites of tumour, such as the foot.

Outcome after Reconstruction of the Proximal Tibia--Complications and Competing Risk Analysis.

Background and Objectives The proximal tibia (pT) is a common site for bone tumors. Improvements in imaging, chemotherapy and surgical technique made limb salvage surgery the treatment of choice. Yet, reconstructions of the pT have been associated with less favorable outcome compared to other parts of the extremities. The aim of this study was to evaluate the outcome of patients with a modular endoprosthetic reconstruction of the pT. Methods Eighty-one consecutive patients with an average age of 29 years underwent endoprosthetic reconstruction of the pT. Postoperative complications were categorized according to the ISOLS classification, and revision-free survival until first complication (any Type 1–5), soft tissue failure (Type 1), aseptic loosening (Type 2), structural failure (Type 3), infection (Type 4), and local tumor progression (Type 5) was estimated by using a Fine-Gray model for competing risk analyses for univariate and multivariable regression with Firth’s bias correction. Results A total of 45 patients (56%) had at least one complication. Cumulative incidence for complication Types 1 to 5 at 5 years with death and amputation as competing events revealed a risk of 41% for the first complication, 14% for Type 1, 16% for Type 2, 11% for Type 3, 17% for Type 4, and 1% for Type 5. Conclusion Despite inclusion of amputation and death as strong competing events, pT replacements are still associated with a high risk of postoperative failures. The results suggest that infection and soft tissue failures (Type 1 and 5) seem to depend from each other. Sufficient soft tissue reconstruction and closure allow better function and reduce the risk of infection as the most prominent complication. The use of a rotating hinge design has significantly reduced structural failures over time.

Interleukin-1 gene cluster variants and abdominal aortic aneurysms A matched case control study

Inflammation is a key factor in the pathogenesis of abdominal aortic aneurysms (AAA). Interleukin 1 (IL-1), a fundamental regulator of the inflammatory cascade, has been shown to be involved in this process. Several functional polymorphisms in the IL-1 gene cluster are known. In this matched case-control study, we investigated a potential association between six genetic variants in IL-1 and IL-1 receptor antagonist (IL-1 RN) with AAA. We enrolled 405 individuals, 135 consecutive patients with AAA were individually age- and sex-matched to 270 patients with coronary artery disease (CAD). Traditional cardiovascular risk factors and IL-1 genotypes were determined, and the distribution of six single nucleotide polymorphisms were compared between patients and controls by multivariable conditional logistic regression analysis: IL-1A (-889) C>T, IL-1A (+4845) G>T, IL-1B (-511) C>T, IL-1B (-31) C>T, IL-1B (+3954) C>T and IL-1RN (+2018) C>T. IL-1A (-889) C>T and IL-1A (+4845) G>T (kappa 0.98,95% CI 0.96 to 1.00), and IL-1B (-511) C>T and IL-1B (-31) C>T (kappa 0.98, 95% CI 0.96 to 1.00) were closely linked, therefore IL-1A (-889) C>T and IL-1B (-31) C>T were not considered for further analyses. None of the 4 remaining polymorphisms showed a significant association with AAA: IL-1RN (+2018) C>T (p = 0.061), IL-1B (+3954) C>T (p = 0.51), IL-1B (-511) C>T (p = 0.61) and IL-1A (+4845) G>T (p = 0.81). No significant first-degree interactions between the genetic variants and AAA were detected. In conclusion,these six genetic variants in the interleukin- I gene cluster do not seem to play a clinically relevant role in the pathogenesis of AAA, although we cannot rule out the existence of higher degree gene-gene or gene-environment interactions.

Do patients with ewing's sarcoma continue with sports activities after limb salvage surgery of the lower extremity?

BackgroundLimb salvage surgery has evolved to become the standard method of treating sarcomas of the extremities with acceptable oncologic results. However, little information exists relative to the activity level or ability to participate in sports after tumor reconstructions.Questions/purposesThe aims of the study were to answer the following questions: (1) Which sports activity levels and what types of sports can be expected in the long term after tumor reconstruction? (2) Which frequency durations are patients with Ewing’s sarcoma able to perform in long-term followup after local control? (3) Do surgical complications affect sports activity level?MethodsThirty patients (13 females, 17 males; mean age, 18 ± 8 years; range, 2–36 years at diagnosis; mean followup 16 ± 6 years [minimum, 5 years]) were included. Tumors were located in the pelvis, femur, tibia, and fibula. Surgical procedures included surgical resections alone (n = 8), surgical resection with biological reconstruction (n = 9), or endoprosthetic reconstruction (n = 13). We assessed UCLA sports activity levels, kinds of sports as well as the frequency per week and the duration of each training unit at long term (minimum followup, 5 years).ResultsIn long-term followup 83% patients (25 of 30) were performing athletic activity regularly. The hours/week of sports depended on type of surgery and were highest after resections in the pelvis and femur (5.8) and were lowest after megaprosthetic reconstruction of the pelvis (1.0). Patients undergoing biologic reconstructions were able to perform high-impact sports. UCLA sports activity levels were high after joint-preserving vascularized fibula for tibia reconstruction (7.4) and after megaprosthetic reconstruction of the lower extremity (6.3–6.4) and were low after tumors located in the fibula (4.2). Complications during followup did not significantly influence sports activity in long-term survivors.ConclusionsLong-term survivors can achieve high levels of sports activity in many instances. Tumor sites are associated with the postoperative sports activity levels. This information can help surgeons counsel patients in terms of athletic expectations after limb salvage reconstruction for patients with Ewing’s sarcoma.Level of EvidenceLevel III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Oncological and surgical outcome after treatment of pelvic sarcomas

Background and objectives Treatment of pelvic tumors remains challenging due to complex anatomy, poor oncological outcome and high complication rates. We sought to investigate the long-term oncological and surgical outcome of these patients. Methods Between 1980 and 2012, 147 patients underwent surgical treatment for pelvic sarcoma. Histological diagnosis was Chondrosarcoma in 54, Ewing’s Sarcoma/PNET in 37, Osterosarcoma in 32 and others in 24 patients. Statistical analysis for the evaluation of oncological and surgical outcome was performed by applying Cox proportional hazards regression and Fine-Gray regression models for competing risk (CR) endpoints. Results The estimated overall survival (OS) to death was 80%, 45% and 37% at 1, 5 and 10 years, respectively. Univariate analyses revealed a statistically significant unadjusted influence of age age (p = 0.038; HR = 1.01), margin (p = 0.043; HR = 0.51) and grade (p = 0.001; HR = 2.27) on OS. Considering the multivariable model, grade (p = 0.005; HR = 3.04) and tumor volume (p = 0.014; HR = 1.18) presented themselves as independent prognostic factors on OS. CR analysis showed a cumulative incidence for major complication of 31% at 5 years. Endoprosthetic reconstruction had a higher risk for experiencing a major complication (p<0.0001) and infection (p = 0.001). Conclusions Pelvic resections are still associated with a high incidence of complications. Patients with pelvic reconstruction and high volume tumors are especially at risk. Consequently, a cautious decision-making process is necessary when indicating pelvic reconstruction, although a restrictive approach to pelvic reconstruction is not necessarily reasonable when the other option is major amputation.

Erratum to “LARS® band and tube for extensor mechanism reconstructions in proximal tibial modular endoprostheses after bone tumors” [Knee 23 (2016) 905–910]☆

☆ Working time of one author (GH) was funded by a grant of the Vienna Science and Technology Fund Project Number LS-018-2011. None of the authors has been influenced by a secondary interest, such as financial gain. DOI of original article: http://dx.doi.org/10.1016/j.knee.2016.04.002. ⁎ Corresponding author at: Department of Orthopaedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Wien, Austria. E-mail addresses: gerhard.hobusch@meduniwien.ac.at (G.M. Hobusch), philipp.funovics@meduniwien.ac.at (P.T. Funovics), cynthia_hourscht@hotmail.com (C. Hourscht), stephan.domayer@meduniwien.ac.at (S.E. Domayer), stephan.puchner@meduniwien.ac.at (S.E. Puchner), martin.dominkus@oss.at (M. Dominkus), reinhard.windhager@akhwien.at (R. Windhager).

LARS® band and tube for extensor mechanism reconstructions in proximal tibial modular endoprostheses after bone tumors ☆

UNLABELLED Wide tumor resections around the proximal tibia (pT) are related to compromised function and high complication rates. This retrospective study aims to present the technique employed as well as functional and surgical outcomes of patients undergoing a Ligament Advanced Reinforcement System (LARS®) reconstruction of the knee extensor apparatus after tumor resection and modular endoprosthetic reconstruction of the proximal tibia. Twenty-five patients who received an artificial ligament after pT resection (11 men and 14 women; mean age, 29years; range 11 to 75years, with a minimum follow-up of 24months) were analyzed regarding the ISOLS failure mode classification. Twenty patients received LARS® during primary surgery, five patients during a revision of a pT modular endoprosthesis. LARS® was available as a band or a tube. The mean extension lag was nine degrees (range, 0 to 30°), the mean flexion was 103° (range, 60 to 130°). The mean extension lag and active flexion in primary implanted LARS were 7.8° and 101° versus secondarily implanted 45° and 115° (p<0.0001; p=0.15). Eleven out of 14 primary implanted LARS® band/tubes (71%) did well with extension lag (0 to 10°). LARS® usage as a band or as a tube showed similar results. The estimated five-year survival of LARS® was 92%. The median survival of LARS® implanted primarily was better than in the case of secondary implantation (p=0.006). Extensor mechanism reconstruction by LARS® band or tube shows excellent function and satisfactory implant survival after primary reconstruction of the extensor mechanism after proximal tibia resection. We experienced no LARS® rupture for only mechanical reasons. LEVEL OF EVIDENCE Level IV retrospective study.

Brazilin blocks catabolic processes in human osteoarthritic chondrocytes via inhibition of NFKB1/p50: BRAZILIN BLOCKS CATABOLIC PROCESSES VIA INHIBITION OF NFKB1/p50

This study aimed to evaluate the chondroprotective and anti‐inflammatory activity of brazilin in human osteoarthritic (OA) cartilage and chondrocytes with particular focus on the nuclear factor‐kappa B (NF‐κB) pathway. Therefore, brazilin was isolated from Caesalpinia sappan and identified using high performance liquid chromatography (HPLC). The effect of brazilin was assessed in cartilage explants treated with 10 ng/ml interleukin (IL)‐1β and 10 ng/ml tumor necrosis factor (TNF)‐α using histological and biochemical glycosaminoglycan (GAG) analyses and in primary chondrocytes treated with 10 ng/ml IL‐1β using RT‐qPCR, ELISA, and Western blot. The involvement of NF‐κB signaling was examined using a human NF‐κB signaling array and in silico pathway analysis. Brazilin was found to reduce the GAG loss from cartilage explants stimulated with IL‐1β and TNF‐α. NF‐κB pathway analysis in chondrocytes revealed NFKB1/p50 as a central player regulating the anti‐inflammatory activities of brazilin. Brazilin suppressed the IL‐1β‐mediated up‐regulation of OA markers and the induction of NFKB1/p50 in chondrocytes. In conclusion, brazilin effectively attenuates catabolic processes in human OA cartilage and chondrocytes—at least in part due to the inhibition of NFKB1/p50—which indicates a chondroprotective potential of brazilin in OA.

C-reactive protein: An independent predictor for dedifferentiated chondrosarcoma: CRP PREDICTS THE DEDIFFERENTIATED CHONDROSARCOMA

Dedifferentiated chondrosarcoma is a rare primary bone malignancy with a very poor prognosis. The aim of the study was to identify pretreatment serum markers as prognostic factors for the overall survival (OS) of patients with dedifferentiated chondrosarcoma. We retrospectively reviewed 33 patients with histologically confirmed dedifferentiated chondrosarcoma treated at our department from 1977 to 2015. Kaplan‐Meier estimation, uni‐ and multivariable Cox proportional hazard model were performed to evaluate the association between serum markers such as the C‐reactive protein and OS. In univariable analysis, CRP was strongly associated with OS (HR 1.35; 95%CI 1.13–1.61; p = 0.001). This association prevailed after adjustment for AJCC tumor stage (HR 1.31; 95%CI 1.02–1.57; p = 0.031) in multivariable analysis. In conclusion, our data gave evidence that baseline CRP is an independent predictor for OS in patients with dedifferentiated chondrosarcoma. CRP could be exploited for the clinical prediction of this disease in the future.