[Osteoporotic fractures of the pelvic ring and their minimally invasive treatment options]. / Osteoporotische Frakturen des Beckenrings und deren minimal-invasive Behandlungsoptionen.

The routine care of osteoporotic fractures of the pelvic ring requires a well-structured treatment algorithm in order to start a stage-appropriate treatment without delay. Nowadays, minimally invasive treatment methods are the gold standard. The minimally invasive dorsal techniques primarily include percutaneous sacroiliac screw osteosynthesis and internal spinopelvic fixation. For minimally invasive treatment from an anterior approach the subcutaneous internal fixator is the method of choice. The primary goal of all forms of treatment, whether conservative or surgical, is the quickest possible painless mobilization and transfer to the familiar environment.

The Role of a Decision Support System in Back Pain Diagnoses: A Pilot Study.

It is the main goal of this study to investigate the concordance of a decision support system and the recommendation of spinal surgeons regarding back pain. 111 patients had to complete the decision support system. Furthermore, their illness was diagnosed by a spinal surgeon. The results showed significant medium relation between the DSS and the diagnosis of the medical doctor. Besides, in almost 50% of the cases the recommendation for the treatment was concordant and overestimation occurred more often than underestimation. The results are discussed in relation to the "symptom checker" literature and the claim of further evaluations.

[Lumbar facet joint disease : Classification, clinical diagnostics, and minimally invasive treatment]. / Das degenerativ veränderte lumbale Facettengelenk : Diagnostik, Klassifikation und minimal-invasive Behandlungsmöglichkeiten.

BACKGROUND: The degeneration of the lumbar facet joint is a multi-factorial process that is closely linked to degeneration of the intervertebral discs and has been implicated as one of the causes of low-back pain of elderly patients in about 15 up to 40% of cases. Moreover, emerging data suggest that increased inflammatory features play an important role in the progression of lumbar facet joint disease and may serve as a link to the afferent pain nerve fibers. OPERATIVE TECHNIQUES: Since the first description in 1975 of minimally invasive treatment of lumbar facet joint disease, different techniques have been developed and used with varying results. Today, the major techniques are thermorhizotomy, cryorhizotomy, and endoscopic or percutaneous facet debridement with different anatomical targets, such as the medial branch of the dorsal ramus or facet joint capsule.

Effects of Glyphosate-, Glufosinate- and Flazasulfuron-Based Herbicides on Soil Microorganisms in a Vineyard.

In a vineyard we examined the effects of broad-spectrum herbicides with three different active ingredients (glyphosate, glufosinate, flazasulfuron) on soil microorganisms. Mechanical weeding served as control treatment. Treatments were applied within grapevine rows and soil samples taken from there in 10-20 cm depth 77 days after application. Fungi were analyzed using classical sequencing technology and bacteria using next-generation sequencing. The number of colony-forming units (CFU) comprising bacteria, yeasts and molds was higher under flazasulfuron compared to all other treatments which had similar CFU levels. Abundance of the fungus Mucor was higher under flazasulfuron than glufosinate and mechanical weeding; Mucor was absent under glyphosate. Several other fungi taxa were exclusively found under a specific treatment. Up to 160 different bacteria species were found - some of them for the first time in vineyard soils. Total bacterial counts under herbicides were on average 260% higher than under mechanical weeding; however due to high variability this was not statistically significant. We suggest that herbicide-induced alterations of soil microorganisms could have knock-on effects on other parts of the grapevine system.

Herbicides in vineyards reduce grapevine root mycorrhization and alter soil microorganisms and the nutrient composition in grapevine roots, leaves, xylem sap and grape juice.

Herbicides are increasingly applied in vineyards worldwide. However, not much is known on potential side effects on soil organisms or on the nutrition of grapevines (Vitis vinifera). In an experimental vineyard in Austria, we examined the impacts of three within-row herbicide treatments (active ingredients: flazasulfuron, glufosinate, glyphosate) and mechanical weeding on grapevine root mycorrhization; soil microorganisms; earthworms; and nutrient concentration in grapevine roots, leaves, xylem sap and grape juice. The three herbicides reduced grapevine root mycorrhization on average by 53% compared to mechanical weeding. Soil microorganisms (total colony-forming units, CFU) were significantly affected by herbicides with highest CFUs under glufosinate and lowest under glyphosate. Earthworms (surface casting activity, density, biomass, reproduction) or litter decomposition in soil were unaffected by herbicides. Herbicides altered nutrient composition in grapevine roots, leaves, grape juice and xylem sap that was collected 11 months after herbicide application. Xylem sap under herbicide treatments also contained on average 70% more bacteria than under mechanical weeding; however, due to high variability, this was not statistically significant. We conclude that interdisciplinary approaches should receive more attention when assessing ecological effects of herbicides in vineyard ecosystems.

ETS-1 Expression Is Hypoxia-independent in Glioblastoma-derived Endothelial and Mesenchymal Stem-like Cells.

BACKGROUND: Tumor cells infiltrating the brain are a typical hallmark of glioblastoma. Invasiveness of glioma cells has been associated with ETS proto-oncogene 1 (ETS-1). In non-glial tumors, ETS-1 expression has been linked to hypoxia. However, it is not known whether hypoxia regulates ETS-1 expression in glioblastoma. MATERIALS AND METHODS: The spatial distribution of ETS-1 expression in primary glioblastoma was assessed using immunohistochemistry. ETS-1 expression in glioblastoma-derived mesenchymal stem-like cells (gbMSLCs) was determined using immunocytochemistry. The effect of hypoxia on ETS-1 expression of gbMSLCs, glioma cell lines and glioblastoma-derived endothelial cells was assessed using polymerase chain reaction and immunoblotting. RESULTS: Our immunohistochemical studies revealed ETS-1 expression in stromal and endothelial glioblastoma cells. Stromal ETS-1 expression in glioblastoma correlated with microvessel density. gbMSLCs were found to express ETS-1. In all examined cell lines, ETS-1 transcription and expression were independent of hypoxia. CONCLUSION: In glioblastoma, ETS-1-expression is not dependent on hypoxia, but correlates with tumor vascularization.

Optional real-time display of intraoperative neurophysiological monitoring in the microscopic field of view: avoiding communication failures in the operating room.

BACKGROUND: The use of intraoperative neurophysiological monitoring (IONM) in neurosurgery has improved patient safety and outcomes. However, a pitfall in the use of IONM remains unsolved. Currently, there is no feasible way for surgeons to interpret IONM waves themselves during operations. Instead, they have to rely on verbal feedback from a neurophysiologist. This method is prone to communication failures, which can lead to delayed or false interpretation of the data. Direct visualization of IONM waves is a way to alleviate this problem and make IONM more effective. METHODS: Microscope-integrated IONM (MI-IONM) was used in 163 cranial and spinal cases. We evaluated the feasibility, system stability and how well the system integrated into the surgical workflow. We used an IONM system that was connected to a surgical microscope. All IONM modalities used at our institution could be visualized as required, superimposed on the surgical field in the eyepiece of the microscope without obstructing the surgeon's field of vision. RESULTS: Use of MI-IONM was safe and reliable. It furthermore provided valuable intraoperative information. The system merely required a short learning curve. Only minor system problems without impact on surgical workflow occurred. MI-IONM proved to be especially useful in surgical cases where careful monitoring of nerve function is required, e.g., cerebellopontine angle surgery. Here, direct assessment of surgical action and IONM wave change was provided to the surgeon, if necessary (on-off control). CONCLUSION: MI-IONM is a useful extension of conventional IONM that provides optional real-time functional information to the surgeon on demand.

Protoporphyrin IX fluorescence and photobleaching during interstitial photodynamic therapy of malignant gliomas for early treatment prognosis.

BACKGROUND AND OBJECTIVE: Interstitial photodynamic therapy (iPDT) of non-resectable recurrent glioblastoma using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) has shown a promising outcome. It remained unclear, however, to what extent inter- and intra-tumoural differences of PpIX concentrations influence the efficacy of iPDT. In the current pilot study, we analysed PpIX concentrations quantitatively and assessed PpIX induced fluorescence and photobleaching intraoperatively. MATERIALS AND METHODS: Five patients harbouring non-resectable glioblastomas were included. ALA (20 or 30 mg/kg body weight) was given 5-8 hours before treatment. Stereotactic biopsies were taken throughout the tumour volume for both histological analysis and determination of PpIX concentrations, which were measured by chemical extraction. Cylindrical light diffusors were stereotactically implanted. Prior to and after irradiation, fluorescence measurements were performed. Outcome measurement was based on clinical and neuro-radiological follow up. RESULTS: In three patients, a strong PpIX fluorescence was seen before treatment, which was completely photobleached after iPDT. High concentrations of PpIX could be detected in viable tumour parts of these patients (mean PpIX uptake per tumour: 1.4-3.0 µM). In the other two patients, however, no or only low PpIX uptake (0-0.6 µM) could be detected. The patients with strong PpIX uptake showed treatment response and long-term clinical stabilisation (no progression in 29, 30 and 36 months), early treatment failure was seen in the remaining two patients (death after 3 and 9 months). CONCLUSIONS: Intra-tumoural PpIX concentrations exhibited pronounced inter- and intra-tumoural variations in glioblastoma, which are directly linked to variable degrees of fluorescence intensity. High intra-tumoural PpIX concentrations with strong fluorescence intensity and complete photobleaching after iPDT seem to be associated with favourable outcome. Real-time monitoring of PpIX fluorescence intensity and photobleaching turned out to be feasible and safe and might be employed for early treatment prognosis of iPDT.

Enhanced analysis of intracerebral arterioveneous malformations by the intraoperative use of analytical indocyanine green videoangiography: technical note.

In cerebral arterioveneous malformations (AVMs) detailed intraoperative identification of feeding arteries, nidal vessels and draining veins is crucial for surgery. Intraoperative imaging techniques like indocyanine green videoangiography (ICG-VAG) provide information about vessel architecture and patency, but do not allow time-dependent analysis of intravascular blood flow. Here we report on our first experiences with analytical indocyanine green videoangiography (aICG-VAG) using FLOW 800 software as a useful tool for assessing the time-dependent intraoperative blood flow during surgical removal of cerebral AVMs. Microsope-integrated colour-encoded aICG-VAG was used for the surgical treatment of a 38-year-old woman diagnosed with an incidental AVM, Spetzler Martin grade I, of the left frontal lobe and of a 26-year-old man suffering from seizures caused by a symptomatic AVM, Spetzler Martin grade III, of the right temporal lobe. Analytical ICG-VAG visualization was intraoperatively correlated with in situ micro-Doppler investigation, as well as preoperative and postoperative digital subtraction angiography (DSA). Analytical ICG-VAG is fast, easy to handle and integrates intuitively into surgical procedures. It allows colour-encoded visualization of blood flow distribution with high temporal and spatial resolution. Superficial major and minor feeding arteries can be clearly separated from the nidus and draining veins. Effects of stepwise vessel obliteration on velocity and direction of AVM blood flow can be objectified. High quality of visualization, however, is limited to the site of surgery. Colour-encoded aICG-VAG with FLOW 800 enables intraoperative real-time analysis of arterial and venous vessel architecture and might, therefore, increase efficacy and safety of neurovascular surgery in a selected subset of superficial AVMs.

The protein tyrosine kinase inhibitor SU5614 inhibits FLT3 and induces growth arrest and apoptosis in AML-derived cell lines expressing a constitutively activated FLT3.

Activating mutations of the protein tyrosine kinase (PTK) FLT3 can be found in approximately 30% of patients with acute myeloid leukemia (AML), thereby representing the most frequent single genetic alteration in AML. These mutations occur in the juxtamembrane (FLT3 length mutations; FLT3-LMs) and the second tyrosine kinase domain of FLT3-TKD and confer interleukin 3 (IL-3)-independent growth to Ba/F3 cells. In the mouse bone marrow transplantation model, FLT3-LMs induce a myeloproliferative syndrome stressing their transforming activity in vivo. In this study, we analyzed the pro-proliferative and antiapoptotic potential of FLT3 in FLT3-LM/TKD-mutation-transformed Ba/F3 cells and AML-derived cell lines. The PTK inhibitor SU5614 has inhibitory activity for FLT3 and selectively induces growth arrest, apoptosis, and cell cycle arrest in Ba/F3 and AML cell lines expressing a constitutively activated FLT3. In addition, the compound reverts the antiapoptotic and pro-proliferative activity of FLT3 ligand (FL) in FL-dependent cells. No cytotoxic activity of SU5614 was found in leukemic cell lines that express a nonactivated FLT3 or no FLT3 protein. At the biochemical level, SU5614 down-regulated the activity of the hyperphosphorylated FLT3 receptor and its downstream targets, signal transducer and activator of (STAT) 3, STAT5, and mitogen-activated protein kinase (MAPK), and the STAT5 target genes BCL-X(L) and p21. Our results show that SU5614 is a PTK inhibitor of FLT3 and has antiproliferative and proapoptotic activity in AML-derived cell lines that endogenously express an activated FLT3 receptor. The selective and potent cytotoxicity of FLT3 PTK inhibitors support a clinical strategy of targeting FLT3 as a new molecular treatment option for patients with FLT3-LM/TKD-mutation(+) AML.

The protein tyrosine kinase inhibitor SU5614 inhibits VEGF-induced endothelial cell sprouting and induces growth arrest and apoptosis by inhibition of c-kit in AML cells.

OBJECTIVE: Angiogenesis, the process of new blood vessel formation, is a critical process during growth and metastasis of solid tumors and might also represent a promising therapeutical target in patients with acute myeloid leukemia (AML). METHODS: In this study, we analyzed the expression of vascular endothelial growth factor receptors (VEGFR)-1/2 and its ligand VEGF in AML cell lines and characterized the inhibitory activity of the protein tyrosine kinase (PTK) inhibitor SU5614 on human endothelial and leukemic cells. RESULTS: Intracellular VEGF expression was detected in 9 of 10 leukemic cell lines. In contrast, VEGFR-1 and VEGFR-2 expression was restricted to 6 and 2 out of 10 cell lines, respectively. Although SU5614 was a potent inhibitor of the VEGF-induced endothelial cell sprouting in vitro, the sensitivity of leukemic cells toward the growth inhibitory activity of the compound was determined by the c-kit, but not by the VEGFR-1/2 expression. SU5614 induced growth arrest and apoptosis in c-kit-expressing Kasumi-1, UT-7, and M-07e cells and inhibited the stem cell factor (SCF)-induced tyrosine phosphorylation of c-kit. The sensitivity of Kasumi-1 cells towards the growth inhibitory activity of SU5614 was caused by an autocrine production of SCF, but not by transforming mutations of c-kit. CONCLUSIONS: Our data provide strong evidence that SU5614 has a dual mode of action, and by direct inhibition of c-kit in AML cells and by inhibition of VEGFR-2 in endothelial cells, it might represent a novel treatment option for patients with c-kit+ AML.