EGFR is not a major driver for osteosarcoma cell growth in vitro but contributes to starvation and chemotherapy resistance

Background Enhanced signalling via the epidermal growth factor receptor (EGFR) is a hallmark of multiple human carcinomas. However, in recent years data have accumulated that EGFR might also be hyperactivated in human sarcomas. Aim of this study was to investigate the influence of EGFR inhibition on cell viability and its interaction with chemotherapy response in osteosarcoma cell lines. Methods We have investigated a panel of human osteosarcoma cell lines regarding EGFR expression and downstream signalling. To test its potential applicability as therapeutic target, inhibition of EGFR by gefitinib was combined with osteosarcoma chemotherapeutics and cell viability, migration, and cell death assays were performed. Results Osteosarcoma cells expressed distinctly differing levels of functional EGFR reaching in some cases high amounts. Functionality of EGFR in osteosarcoma cells was proven by EGF-mediated activation of both MAPK and PI3K/AKT pathway (determined by phosphorylation of ERK1/2, AKT, S6, and GSK3). The EGFR-specific inhibitor gefitinib blocked EGF-mediated downstream signal activation. At standard in vitro culture conditions, clinically achievable gefitinib doses demonstrated only limited cytotoxic activity, however, significantly reduced long-term colony formation and cell migration. In contrast, under serum-starvation conditions active gefitinib doses were distinctly reduced while EGF promoted starvation survival. Importantly, gefitinib significantly supported the anti-osteosarcoma activities of doxorubicin and methotrexate regarding cell survival and migratory potential. Conclusion Our data suggest that EGFR is not a major driver for osteosarcoma cell growth but contributes to starvation- and chemotherapy-induced stress survival. Consequently, combination approaches including EGFR inhibitors should be evaluated for treatment of high-grade osteosarcoma patients.(VLID)486733

Periprosthetic Joint Infection of Shoulder Arthroplasties: Diagnostic and Treatment Options

Periprosthetic joint infection (PJI) is one of the most frequent reasons for painful shoulder arthroplasties and revision surgery of shoulder arthroplasties. Cutibacterium acnes (Propionibacterium acnes) is one of the microorganisms that most often causes the infection. However, this slow growing microorganism is difficult to detect. This paper presents an overview of different diagnostic test to detect a periprosthetic shoulder infection. This includes nonspecific diagnostic tests and specific tests (with identifying the responsible microorganism). The aspiration can combine different specific and nonspecific tests. In dry aspiration and suspected joint infection, we recommend a biopsy. Several therapeutic options exist for the treatment of PJI of shoulder arthroplasties. In acute infections, the options include leaving the implant in place with open debridement, septic irrigation with antibacterial fluids like octenidine or polyhexanide solution, and exchange of all removable components. In late infections (more than four weeks after implantation) the therapeutic options are a permanent spacer, single-stage revision, and two-stage revision with a temporary spacer. The functional results are best after single-stage revisions with a success rate similar to two-stage revisions. For single-stage revisions, the microorganism should be known preoperatively so that specific antibiotics can be mixed into the cement for implantation of the new prosthesis and specific systemic antibiotic therapy can be applied to support the surgery

Body image and self-esteem in lower-limb amputees.

BACKGROUND: Limb amputation is often an inevitable procedure in the advanced condition of various diseases and poses a dramatic impact on a patient's life. The aim of the present study is to analyze the impact of lower-limb amputations on aesthetic factors such as body image and self-esteem as well as quality of life (QoL). METHODS: 298 patients (149 uni- or bilateral lower-limb amputees and 149 controls) were included in this cross-sectional study in three centers. Demographic data was collected and patients received a 118-item questionnaire including the Multidimensional Body-Self Relations Questionnaire (MBSRQ), the Rosenberg Self-esteem (RSE) scale and the SF-36 Health Survey (QoL). ANOVA and student's t-test were used for statistical analysis. RESULTS: Unilateral lower-limb amputees showed a significant lower MBSRQ score of 3.07±0.54 compared with 3.41±0.34 in controls (p<0.001) and a lower score in the RSE compared to controls (21.63±4.72 vs. 21.46±5.86). However, differences were not statistically significant (p = 0.36). Patients with phantom pain sensation had a significantly reduced RSE (p = 0.01). The SF-36 health survey was significantly lower in patients with lower-limb amputation compared to controls (42.17±14.47 vs. 64.05±12.39) (p<0.001). CONCLUSION: This study showed that lower-limb amputations significantly influence patients' body image and QoL. Self-esteem seems to be an independent aspect, which is not affected by lower-limb amputation. However, self-esteem is influenced significantly by phantom pain sensation

International Orthopaedics / Multiplex PCR Unyvero i60 ITI application improves detection of low-virulent microorganisms in periprosthetic joint infections

Purpose The aim of this study was to evaluate the pre-operative performance of an automated multiplex PCR (mPCR) system in patients with suspected periprosthetic joint infection (PJI). Methods Under sterile conditions, synovial fluid samples from patients with a suspected PJI were collected pre-operatively. One hundred eighty microliter of the aspirate was used for analysis in the mPCR. The remaining joint fluid was sent for microbiological analysis. PJI was diagnosed by using the Musculoskeletal Infection Society (MSIS) criteria. Total percentage agreement and Cohens kappa coefficient were calculated to measure overall agreement. Results Overall, 90 patients with a suspected PJI were included. Using MSIS criteria, 38 (42%) patients were classified as septic. Total percent agreement between mPCR and synovial fluid culture was 86% with a Cohens kappa of 0.68. The mPCR and synovial fluid culture showed sensitivities of 71% and 84%, respectively. Combined evaluation provided an even higher sensitivity of 92%. While Cutibacterium spp. were detected five times by mPCR, it could only be cultured once. A higher detection rate of CoNS by mPCR (n=7) compared to conventional culture (n=5) was also demonstrated. In comparison to synovial fluid culture, the mPCR missed Staphylococcus aureus five times. Conclusion With a moderate agreement between synovial fluid mPCR and culture, the mPCR system could be a useful adjunct in diagnosing a PJI pre-operatively. Due to faster availability of results and a higher detection rate of low-virulent microorganisms, it can complement conventional culture.(VLID)363848

Results of the MBSRQ in unilateral lower-limb amputees and controls.

<p>Box plot showing the distribution of the MBSRQ in unilateral lower-limb amputees (left) and controls (right). Horizontal red lines indicate medians; blue boxes specify inter-quartile ranges and dashed lines the ranges without outliers.</p

Result of the SF-36 - QOL in unilateral lower-limb amputees and controls.

<p>Box plot showing the distribution of the SF-36 in unilateral lower-limb amputees (left) and controls (right). Horizontal red lines indicate medians; blue boxes specify inter-quartile ranges and dashed lines the ranges without outliers.</p

The influence of antibiotic-loaded cement spacers on the risk of reinfection after septic two-stage hip revision surgery

Purpose The aim of this study was the evaluation of possible outcome differences of patients undergoing two-stage hip exchange with antibiotic-loaded spacers, compared to patients without an interim spacer implantation. Methods We evaluated 46 patients undergoing two-stage hip revision surgery. Twenty-five patients received an interim ALS. Additional to a KaplanMeier survival analysis, a competing risk analysis was performed to estimate the cumulative incidence function for re-revisions due to infection accounting for death as a competing event. Results Nine patients (seven non-ALS vs. two ALS) had to undergo re-revision surgery due to reinfection of the hip joint. The non-ALS group showed a risk of re-revision of 19% (95% CI 538%) at 12 and 24 months and 30% (95% CI 1251%) at 36 months. The group with ALS implantation displayed a 0% risk of re-revision surgery in the first 36 months. The Gray test revealed a significant difference in the cumulative incidence between both observed groups (p = 0.026). Conclusion Our findings suggest that ALS implantation significantly reduces the risk of reinfection after two-stage hip revision surgery.(VLID)357000

Results of the QoL – SF-36 and its subscales.

<p>Results of the QoL – SF-36 and its subscales.</p

Results of the MBSRQ and its subscales.

<p>Results of the MBSRQ and its subscales.</p