Vertebral osteomyelitis with Campylobacter jejuni - a case report and review of the literature of a very rare disease.

Infections with Campylobacter species mainly cause gastrointestinal disease and are usually self-limiting. Systemic complications such as bacteremia and osteoarticular infections are rare. Here we report a very rare case of a vertebral osteomyelitis due to C. jejuni, and we reviewed the literature for similar cases, identifying six other cases. Therapy should be guided on resistance testing if available due to emerging resistance rates, especially to fluoroquinolones. Azithromycin may be a treatment option for C. jejuni spondylodiscitis.

Endovascular embolisation is a successful and safe treatment for post-operative arterial complications after total hip arthroplasty and revision surgery.

PURPOSE: Arterial complications are rare but clinically critical during or following total hip arthroplasty (THA) surgery. They usually require secondary interventions, either through open or endovascular approaches. In a retrospective study, we analysed indications for, as well as success and safety of, endovascular embolisation for arterial complications after THA. METHODS: We reviewed all arterial complications that had occurred through THA surgery and been treated by endovascular embolisation. We analysed angiographic findings, endovascular treatment, location in relation to the surgical approach and success of the interventions. RESULTS: Between 1997 and 2013 we performed 3,891 THAs at our hospital. We identified 14 patients with acute arterial complications treated by minimally invasive endovascular embolisation. Clinical findings included swelling of the ipsilateral leg, pain, prolonged wound bleeding, decreased haemoglobin and/or haemodynamic instability. Angiography revealed pseudoaneurysm in 11 patients, arteriovenous fistulas in two and extravasation of contrast media in one. Two patients showed no signs of acute bleeding. Twelve patients were treated, each with a single session of endovascular embolisation; in two additional patients, the haematoma was evacuated. No complications from the endovascular treatment were observed in this series. CONCLUSION: Endovascular embolisation is a safe and successful minimally-invasive method to treat arterial injuries occurring through THA. Therefore, it should be considered as a first-line option of treatment for those injuries.

The use of a head-mounted display in oral implantology: a feasibility study.

PURPOSE: To compare the accuracy of a navigation system for oral implantology using either a head-mounted display (HMD) or a monitor as a device for visualization. METHODS: Drilling experiments in plastic mandibles were performed by seven investigators supported by a navigation system using an HMD. A set of drilling experiments was carried out using a traditional monitor setup as standard of reference. Prior to the experiments, CT scans of the mandibles were performed. Positions of the boreholes were determined with the planning software Mimics[Formula: see text]. In order to find the correct positions of the boreholes, individuals had to match two pairs of crosshairs. By an infrared tracking device, the navigation system was able to spot the artificial jaw and the angular piece of the drill allowing for the navigation. After the experiments, a second CT scan was acquired: (i) to identify the beginning and the end of the boreholes, (ii) to compare the positions of the planned implant and the boreholes and (iii) to calculate the deviations. RESULTS: Overall deviation of the starting point of the borehole was 1.24 ± 0.84 mm for the HMD and 1.12 ± 0.68 mm for the monitor, 2.68 ± 1.65 mm of the end point of the borehole for the HMD and 2.46 ± 1.34 mm for the monitor. The mean deviation of the axis was 4.68◦ ± 3.7◦ for the HMD and 4.53◦ ± 4.17◦ for the monitor. CONCLUSIONS: As overall accuracies do not differ significantly, the two methods seem to be equal. Personal skills seem to be crucial as the results show remarkable differences among the test persons. The results of our study demonstrate that the use of an HMD has no major drawbacks compared to the monitor setting. The striking advantage is that the surgeon is no longer obliged to turn his head away from the operation site during navigation, as all data relevant for the procedure are superimposed on the image of the real world in his field of view.

MR-based hypoxia measures in human glioma.

Hypoxia plays a central role in tumor stem cell genesis and is related to a more malignant tumor phenotype, therapy resistance (e.g. in anti-angiogenic therapies) and radio-insensitivity. Reliable hypoxia imaging would provide crucial metabolic information in the diagnostic work-up of brain tumors. In this study, we applied a novel BOLD-based MRI method for the measurement of relative oxygen extraction fraction (rOEF) in glioma patients and investigated potential benefits and drawbacks. Forty-five glioma patients were examined preoperatively in a pilot study on a 3T MR scanner. rOEF was calculated from quantitative transverse relaxation rates (T2, T2*) and cerebral blood volume (CBV) using a quantitative BOLD approach. rOEF maps were assessed visually and by means of a volume of interest (VOI) analysis. In six cases, MRI-targeted biopsy samples were analyzed using HIF-1α-immunohistochemistry. rOEF maps could be obtained with a diagnostic quality. Focal spots with high rOEF values were observed in the majority of high-grade tumors but in none of the low-grade tumors. VOI analysis revealed potentially hypoxic tumor regions with high rOEF in contrast-enhancing tumor regions as well as in the non-enhancing infiltration zone. Systematic bias was found as a result of non-BOLD susceptibility effects (T2*) and contrast agent leakage affecting CBV. Histological samples demonstrated reasonable correspondence between MRI characteristics and HIF-1α-staining. The presented method of rOEF imaging is a promising tool for the metabolic characterization of human glioma. For the interpretation of rOEF maps, confounding factors must be considered, with a special focus on CBV measurements in the presence of contrast agent leakage. Further validation involving a bigger cohort and extended immuno-histochemical correlation is required.

Aurora kinases A and B are up-regulated by Myc and are essential for maintenance of the malignant state.

Myc oncoproteins promote continuous cell growth, in part by controlling the transcription of key cell cycle regulators. Here, we report that c-Myc regulates the expression of Aurora A and B kinases (Aurka and Aurkb), and that Aurka and Aurkb transcripts and protein levels are highly elevated in Myc-driven B-cell lymphomas in both mice and humans. The induction of Aurka by Myc is transcriptional and is directly mediated via E-boxes, whereas Aurkb is regulated indirectly. Blocking Aurka/b kinase activity with a selective Aurora kinase inhibitor triggers transient mitotic arrest, polyploidization, and apoptosis of Myc-induced lymphomas. These phenotypes are selectively bypassed by a kinase inhibitor-resistant Aurkb mutant, demonstrating that Aurkb is the primary therapeutic target in the context of Myc. Importantly, apoptosis provoked by Aurk inhibition was p53 independent, suggesting that Aurka/Aurkb inhibitors will show efficacy in treating primary or relapsed malignancies having Myc involvement and/or loss of p53 function.

Antifungal therapy with itraconazole impairs the anti-lymphoma effects of rituximab by inhibiting recruitment of CD20 to cell surface lipid rafts.

Immunotherapy with rituximab alone or in conjunction with chemotherapy has significantly improved the treatment outcome of B-cell lymphoma patients. Nevertheless, a subpopulation of patients does not respond to rituximab. The reason for treatment failure as well as the exact mechanism of action is still uncertain. The function of rituximab has long been associated with the partitioning of CD20 molecules to membrane microdomains. Here, we show that concomitant antifungal treatment with itraconazole impairs the rituximab anti-lymphoma effect both in vitro and in vivo. At the molecular level, recruitment of CD20 to lipid rafts is inhibited in the presence of itraconazole. Furthermore, calcium influx, which is crucial for rituximab-mediated cell death, was nearly completely abolished by itraconazole treatment. In contrast, the antifungal drug caspofungin did not inhibit CD20 recruitment to lipid rafts, nor did it affect calcium influx or the cytotoxic effect of rituximab. The finding that itraconazole also abolished the cytotoxic effects of other therapeutic antibodies directed against lipid raft-associated molecules (i.e., CD20 and CD52) but not those against the non-raft-associated molecule CD33 further supported our proposed mechanism of action. Our results argue that concomitant medications must be adjusted carefully to achieve optimal antitumor effects with monoclonal antibodies.

Imaging proliferation to monitor early response of lymphoma to cytotoxic treatment.

PURPOSE: Positron emission tomography with the thymidine analogue 3'-deoxy-3'-[18F]fluorothymidine (FLT) has been reported to closely reflect lymphoma proliferation in vivo. In this preclinical study, we have investigated if FLT can also be utilized for imaging therapy-induced alterations of the nucleoside metabolism and if FLT is a surrogate marker for early response to cytotoxic treatment. MATERIALS AND METHODS: Immunodeficient mice bearing high-grade lymphoma xenotransplants were treated with the cytotoxic agent doxorubicin (day 0). In the time course of day +1 to +9, antiproliferative effects were assessed non-invasively with FLT-PET and correlated to changes of the proliferation fraction and induction of apoptosis, as assessed by immunohistochemistry. RESULTS: Tumor growth in untreated animals was significantly higher than in treated animals. In FLT-PET scans, these observations correlated with a significant decrease of tumor-to-background ratio in the therapy group already at day 1. Likewise, median tumor-to-muscle ratio of FLT uptake already declined at day 1. The proliferation fraction assessed by Ki-67 immunohistochemistry decreased after chemotherapy, while activated caspase 3 increased, suggesting both cell cycle arrest and induction of apoptosis as underlying mechanisms of the observed PET-signal alterations. CONCLUSION: In a lymphoma xenotransplant model, we show that positron emission tomography using the proliferation marker FLT is suitable to detect early response to cytotoxic treatment. A significant decrease of FLT uptake but not tumor growth was detectable already 24 h after therapy and correlated with reduced proliferation and induction of apoptosis. Thus, FLT-PET has a potential for imaging early response to treatment in malignant lymphoma.