ETS1 induces transforming growth factor ß signaling and promotes epithelial-to-mesenchymal transition in prostate cancer cells.

Expression of the transcriptional regulator, E26 transformation-specific 1 (ETS1), is elevated in human prostate cancers, and this is associated with more aggressive tumor behavior and a rapid progression to castrate-resistant disease. Multiple ETS1 isoforms with distinct biological activities have been characterized and in 44 matched nonmalignant and malignant human prostate specimens, messenger RNAs for two ETS1 isoforms, ETS1p51 and ETS1p42, were detected, with ETS1p51 levels significantly lower in prostate tumor compared to matched nonmalignant prostate tissues. In contrast, ETS1p51 protein, the only ETS1 isoform detected, was expressed at significantly higher levels in malignant prostate. Analysis of epithelial-to-mesenchymal transition (EMT)-associated genes regulated following overexpression of ETS1p51 in the LNCaP prostate cancer cell line predicted promotion of transforming growth factor ß (TGFß) signaling and of EMT. ETS1p51 overexpression upregulated cellular levels of the EMT transcriptional regulators, ZEB1 and SNAIL1, resulted in reduced expression of the mesenchymal marker vimentin with concomitantly elevated levels of claudin 1, an epithelial tight junction protein, and increased prostate cancer cell migration and invasion. ETS1p51-induced activation of the pro-EMT TGFß signaling pathway that was predicted in polymerase chain reaction arrays was verified by demonstration of elevated SMAD2 phosphorylation following ETS1p51 overexpression. Attenuation of ETS1p51 effects on prostate cancer cell migration and invasion by inhibition of TGFß pathway signaling indicated that ETS1p51 effects were in part mediated by induction of TGFß signaling. Thus, overexpression of ETS1p51, the predominant ETS1 isoform expressed in prostate tumors, promotes an EMT program in prostate cancer cells in part via activation of TGFß signaling, potentially accounting for the poor prognosis of ETS1-overexpressing prostate tumors.

Activity of ABCG2 Is Regulated by Its Expression and Localization in DHT and Cyclopamine-Treated Breast Cancer Cells.

Elevated expression of the efflux transporter, ATP-binding cassette subfamily G isoform 2 (ABCG2) on the plasma membrane of cancer cells contributes to the development of drug resistance and is a key characteristic of cancer stem cells. In this study, gene expression analysis identified that treatment of the MCF-7 and T-47D breast cancer cell lines with the androgen, 5α-dihydrotestosterone (DHT), and the Hedgehog signaling inhibitor, cyclopamine downregulated ABCG2 mRNA levels. In MCF-7 cells, and in Hoechst 33342(lo) /CD44(hi) /CD24(lo) breast cancer stem-like cells isolated from MCF-7 cultures, ABCG2 was accumulated in cell-to-cell junction complexes and in large cytoplasmic aggresome-like vesicles. DHT treatments, which decreased cellular ABCG2 protein levels, led to diminished ABCG2 localization in both cell-to-cell junction complexes and in cytoplasmic vesicles. In contrast, cyclopamine, which did not alter ABCG2 protein levels, induced accumulation of ABCG2 in cytoplasmic vesicles, reducing its localization in cell-to-cell junction complexes. The reduced localization of ABCG2 at the plasma membrane of MCF-7 cells was associated with decreased efflux of the ABCG2 substrate, mitoxantrone, and increased sensitivity of cyclopamine-treated cultures to the cytotoxic effects of mitoxantrone. Together, these findings indicate that DHT and cyclopamine reduce ABCG2 activity in breast cancer cells by distinct mechanisms, providing evidence to advocate the adjunct use of analogous pharmaceutics to increase or prolong the efficacy of breast cancer treatments. J. Cell. Biochem. 117: 2249-2259, 2016. © 2016 Wiley Periodicals, Inc.

Poly(N,N-dimethylaminoethyl methacrylate) Brushes: pH-Dependent Switching Kinetics of a Surface-Grafted Thermoresponsive Polyelectrolyte.

The temperature-dependent switching behavior of poly(N,N-dimethylaminoethyl methacrylate) brushes in alkaline, neutral, and acidic solutions is examined. A novel microscopic laser temperature-jump technique is employed in order to study characteristic thermodynamic and kinetic parameters. Static laser micromanipulation experiments allow one to determine the temperature-dependent variation of the swelling ratio. The data reveal a strong shift of the volume phase transition of the polymer brushes to higher temperatures when going from pH = 10 to pH = 4. Dynamic laser micromanipulation experiments offer a temporal resolution on a submillisecond time scale and provide a means to determine the intrinsic rate constants. Both the swelling and the deswelling rates strongly decrease in acidic solutions. Complementary experiments using in situ atomic force microscopy show an increased polymer layer thickness at these conditions. The data are discussed on the basis of pH-dependent structural changes of the polymer brushes including protonation of the amine groups and conformational rearrangements. Generally, repulsive electrostatic interactions and steric effects are assumed to hamper and slow down temperature-induced switching in acidic solutions. This imposes significant restrictions for smart polymer surfaces, sensors, and devices requiring fast response times.

The use of cognitive load theory to assist in the teaching of electrocardiogram interpretation within paramedical science education.

BACKGROUND: Paramedics are expected to record electrocardiograms (ECGs) as part of their clinical assessment; however, it is an extremely difficult skill to learn and understand as it has a high intrinsic cognitive load which can also be challenging to teach effectively. AIMS: This article will explore the use of cognitive load theory to assist in the teaching of ECG interpretation within the context of paramedical education. DESCRIPTION: Cognitive load theory can be useful to aid teaching within complex medical and health science domains including clinical skills teaching. CONCLUSIONS: The application of cognitive load theory to the teaching of ECG interpretation can be useful as it allows for the development of understanding, building schemata linking information currently being learned to knowledge already gained within the long-term memory, which can maximise germane load by the appropriate selection of intrinsic load, minimising extraneous load therefore not overloading the working memory.

Hofmeister effect of sodium halides on the switching energetics of thermoresponsive polymer brushes.

A laser temperature-jump technique is used to probe the impact of sodium halides on the temperature-dependent switching kinetics and thermodynamics of poly(N-isopropylacrylamide) brushes. An analysis on the basis of a two-state model reveals van't Hoff enthalpy and entropy changes. Sodium halides increase the endothermicity and the entropic gain of the switching process below and above Tc following the Hofmeister series: NaCl > NaBr > NaI. In contrast, enthalpic and entropic changes at Tc remain virtually unaffected. This provides an unprecedented insight into the underlying switching energetics of this classic stimuli-responsive polymer. Because of its model character, these results represent an essential reference on the way to unpuzzle the molecular driving forces of the Hofmeister effect.

Adequacy of cytology and small biopsy samples obtained with rapid onsite evaluation (ROSE) for predictive biomarker testing in non-small cell lung cancer.

Complete biomarker workup of non-small cell lung cancer (NSCLC) specimens is essential for appropriate and timely clinical management decisions. This can be challenging to achieve from small cytology and histology specimens, with increasing numbers of molecular and immunohistochemical biomarkers required. We conducted a 5 year retrospective audit of cases at our institution to assess the diagnostic and biomarker testing adequacy rates, particularly those specimens obtained with rapid onsite evaluation (ROSE), performed by a cytopathologist and a cytology scientist or pathology trainee, including all endobronchial ultrasound guided transbronchial needle aspirations (EBUS-TBNA), CT guided lung fine needle aspirations (FNA) and CT guided lung core biopsies. A total of 5,354 cases were identified, of which 92.2% had sufficient material for diagnosis. Of the 1506 cases identified with a recorded diagnosis of lung adenocarcinoma or NSCLC, not otherwise specified, 1001 (66.5%) had biomarker testing requested. Sufficient material was available in 89.5% of cases for a complete biomarker workup which included EGFR and KRAS mutational testing (all cases), ALK, ROS1 and PD-L1 immunohistochemistry (all cases), and ALK and ROS1 FISH (as required). For EGFR and KRAS mutational testing across both cytology and histology specimens, 99% of cases were sufficient. Of the samples in which a complete biomarker workup was unable to be performed, approximately half were only insufficient due to inadequate numbers of tumour cells for PD-L1 immunohistochemistry. Excluding PD-L1 IHC, 952 (95.1%) of samples obtained with ROSE were sufficient for the remainder of the testing requirements. Next generation sequencing using a 33 gene custom AmpliSeq panel was achieved in up to 72% of cases. In conclusion, small cytology and histology specimens obtained with ROSE are suitable for predictive biomarker testing in NSCLC, although attention needs to be paid to obtaining sufficient cells (>100) for PD-L1 immunohistochemistry.

Particle size distribution: An experimental study using southern African reduction methods and raw materials.

We experimentally created a particle size dataset that is based on reduction sequences and raw materials typical of the Middle and Later Stone Age in southern Africa. The reason for creating this new dataset is that current particle size frameworks are based, almost exclusively, on flint and western European knapping methods. We produced the dataset using knapping methods and raw materials frequently encountered in the southern African archaeological record because we wanted to test whether it has the same distribution as particle size datasets experimentally created in Europe, and to initialise the production of a database for use in the analysis of lithic assemblages from southern African Late Pleistocene deposits. We reduced 117 cores of quartz, quartzite, jasper, chalcedony, hornfels, and rhyolite. The knapping methods selected were unidirectional, discoidal, Levallois recurrent and bipolar flaking. In this article we compare this new particle size distribution dataset with the results obtained from previous experiments. We found that the southern African dataset shows a wider size range distribution, which seems to be explained by differences in knapping methods and raw materials. Our results show that there is overlap between the distribution of the southern African experimental knapping dataset and the sorting experiment conducted by Lenoble on flint artefacts in a runoff context. This article shows that a particle size analysis is not sufficient on its own to assess the perturbation of an archaeological assemblage and must be coupled with other analytical tools.

Enhancing the learning of evolutionary anthropology skills by combining student-active teaching with actual and virtual immersion of Master's students in fieldwork, laboratory practice, and dissemination.

Higher education in evolutionary anthropology involves providing students with in-depth knowledge of biological and cultural heritage sites and collections that are frequently inaccessible. Indeed, most sites, fossils, and archaeological remains can be visited or manipulated only rarely and solely by specialists with extensive experience. Owing to the development of 3D and medical imaging techniques, this fragile heritage is now more widely accessible, and in a dynamic way. However, exclusive adoption of virtual teaching and learning has a negative impact on student engagement and, naturally, on exchanges with instructors, and thus cannot be used without some reservations. In the ITAP (Immersion dans les Terrains de l'Anthropologie biologique et de la Préhistoire) project of the higher education STEP (Soutien à la Transformation et à l'Expérimentation Pédagogiques) transformation program at the University of Bordeaux, we combine student-active teaching with Master's students fully immersed in ongoing fieldwork, laboratory study, and dissemination of research results in order to develop more individually shaped learning curricula and to foster both professional and new interdisciplinary skills. Here, we present examples of experiments conducted in the ITAP project using both authentic and virtual collections of archaeological, experimental, and reference materials that help to break down the barriers between research activities and higher education, as well as providing a more general appraisal of the appropriate use of virtual tools in higher education by combining them with real-life situations.

Imaging of the Osteoporotic Spine - Quantitative Approaches in Diagnostics and for the Prediction of the Individual Fracture Risk.

Osteoporosis is a highly prevalent systemic skeletal disease that is characterized by low bone mass and microarchitectural bone deterioration. It predisposes to fragility fractures that can occur at various sites of the skeleton, but vertebral fractures (VFs) have been shown to be particularly common. Prevention strategies and timely intervention depend on reliable diagnosis and prediction of the individual fracture risk, and dual-energy X-ray absorptiometry (DXA) has been the reference standard for decades. Yet, DXA has its inherent limitations, and other techniques have shown potential as viable add-on or even stand-alone options. Specifically, three-dimensional (3 D) imaging modalities, such as computed tomography (CT) and magnetic resonance imaging (MRI), are playing an increasing role. For CT, recent advances in medical image analysis now allow automatic vertebral segmentation and value extraction from single vertebral bodies using a deep-learning-based architecture that can be implemented in clinical practice. Regarding MRI, a variety of methods have been developed over recent years, including magnetic resonance spectroscopy (MRS) and chemical shift encoding-based water-fat MRI (CSE-MRI) that enable the extraction of a vertebral body's proton density fat fraction (PDFF) as a promising surrogate biomarker of bone health. Yet, imaging data from CT or MRI may be more efficiently used when combined with advanced analysis techniques such as texture analysis (TA; to provide spatially resolved assessments of vertebral body composition) or finite element analysis (FEA; to provide estimates of bone strength) to further improve fracture prediction. However, distinct and experimentally validated diagnostic criteria for osteoporosis based on CT- and MRI-derived measures have not yet been achieved, limiting broad transfer to clinical practice for these novel approaches. KEY POINTS:: · DXA is the reference standard for diagnosis and fracture prediction in osteoporosis, but it has important limitations.. · CT- and MRI-based methods are increasingly used as (opportunistic) approaches.. · For CT, particularly deep-learning-based automatic vertebral segmentation and value extraction seem promising.. · For MRI, multiple techniques including spectroscopy and chemical shift imaging are available to extract fat fractions.. · Texture and finite element analyses can provide additional measures for vertebral body composition and bone strength.. CITATION FORMAT: · Sollmann N, Kirschke JS, Kronthaler S et al. Imaging of the Osteoporotic Spine - Quantitative Approaches in Diagnostics and for the Prediction of the Individual Fracture Risk. Fortschr Röntgenstr 2022; 194: 1088 - 1099.

ETS1 regulates NKX3.1 5' promoter activity and expression in prostate cancer cells.

BACKGROUND: NKX3.1 controls the differentiation and proliferation of prostatic epithelial cells both during development and in the adult, while its expression is frequently downregulated in prostate cancers. Transcriptional control of NKX3.1 expression and in particular, factors that function via the NKX3.1 5' proximal promoter are poorly characterized. METHODS: Deletion reporter analyses, bioinformatics, electromobility shift assays (EMSA), chromatin immunoprecipitation (ChIP) and Western blotting were performed to identify and functionally characterize sites of transcription factor binding within the initial 2,062 bp of the NKX3.1 5' promoter. RESULTS: Deletion reporter studies of the 2,062 bp NKX3.1 5' promoter sequence localized positive transcriptional activity between -1069 and -993. Bioinformatic analyses identified the presence of two overlapping ETS1 binding sites within this region, designated EBS1 and EBS2, which exhibited 82% and 74% homology, respectively, to the ETS consensus binding sequence. EMSA and supershift assays indicated binding of both endogenous ETS1 and a recombinant GST-ETS1 protein solely to EBS1, a result that was confirmed in vivo by ChIP analysis. ETS1 overexpression transactivated NKX3.1 promoter reporter activity and upregulated endogenous NKX3.1 mRNA and protein levels in the LNCaP prostate cancer cell line, demonstrating a functional role for ETS1 in the regulation of NKX3.1 expression. CONCLUSIONS: ETS1 upregulation of NKX3.1 expression in LNCaP cells is mediated in part via its interaction with an EBS located in the NKX3.1 5' proximal promoter. ETS1 may regulate NKX3.1 during prostate development, with the aberrant ETS1 expression and cellular localization frequently observed in human prostate tumors potentially contributing to the abnormal expression of NKX3.1.

Androgen regulation of the prostatic tumour suppressor NKX3.1 is mediated by its 3' untranslated region.

The homeodomain transcription factor NKX3.1 is a prostate-specific tumour suppressor, expression of which is reduced or undetectable in the majority of metastatic prostate tumours. In the normal prostate and in prostate cancer cells, NKX3.1 expression is under tight androgenic control that we have shown to be mediated by its ~2.5 kb 3'UTR (3' untranslated region). Reporter deletion analysis of the NKX3.1 3'UTR identified three regions that were transactivated by DHT (5alpha-dihydrotestosterone) in the AR (androgen receptor)-expressing prostate cancer cell line LNCaP. Reversal of DHT effects by the anti-androgen bicalutamide supported an AR-mediated mechanism, and bioinformatic analysis of the NKX3.1 3'UTR identified canonical AREs (androgen-response elements) in each of the androgen-responsive regions. EMSAs (electrophoretic mobility-shift assays) indicated binding of the AR DNA-binding domain to two of the AREs, a proximal ARE at +2378-2392 from the transcription start site, and a more distal ARE at +3098-3112. ChIP (chromatin immunoprecipitation) analysis provided further evidence of ligand-dependent recruitment of endogenous AR to sequence encompassing each of the two elements, and site-directed mutagenesis and deletion analysis confirmed the contribution of each of the AREs in reporter assays. The present studies have therefore demonstrated that the NKX3.1 3'UTR functions as an androgen-responsive enhancer, with the proximal ARE contributing the majority and the distal ARE providing a smaller, but significant, proportion of the androgen responsiveness of the NKX3.1 3'UTR. Characterization of androgen-responsive regions of the NKX3.1 gene will assist in the identification of transcriptional regulatory mechanisms that lead to the deregulation of NKX3.1 expression in advanced prostate cancers.

A design of experiments for statistically predicting risk of adverse health effects on drivers exposed to vertical vibrations.

An injury risk factor (IRF), which indicates the risk of adverse health effect to lumbar rachis arising from mechanical vibrations, is developed. Experiments have been conducted that consider acceleration levels at the seat of drivers, posture, morphology, density, damping rate and body mass as independent variables. A parametric finite-element model of the lumbar rachis has been generated. It is shown that the IRF increases with ageing and an IRF of 30% is proposed as a threshold for fatigue purposes. This level is reached if a peak acceleration level greater than 3 m/s² is applied to a light (55 kg) and an old driver with a low bone density and a damping rate of 20%. This vibration threshold must be reduced to 2.7 m/s² if the driver?s weight increases to 75 kg and to 2 m/s² if the driver is heavy (98 kg).

LUMOS - Low and Intermediate Grade Glioma Umbrella Study of Molecular Guided TherapieS at relapse: Protocol for a pilot study.

INTRODUCTION: Grades 2 and 3 gliomas (G2/3 gliomas), when combined, are the second largest group of malignant brain tumours in adults. The outcomes for G2/3 gliomas at progression approach the dismal outcomes for glioblastoma (GBM), yet there is a paucity of trials for Australian patients with relapsed G2/3 gliomas compared with patients with GBM. LUMOS will be a pilot umbrella study for patients with relapsed G2/3 gliomas that aims to match patients to targeted therapies based on molecular screening with contemporaneous tumour tissue. Participants in whom no actionable or no druggable mutation is found, or in whom the matching drug is not available, will form a comparator arm and receive standard of care chemotherapy. The objective of the LUMOS trial is to assess the feasibility of this approach in a multicentre study across five sites in Australia, with a view to establishing a national molecular screening platform for patient treatment guided by the mutational analysis of contemporaneous tissue biopsies METHODS AND ANALYSIS: This study will be a multicentre pilot study enrolling patients with recurrent grade 2/3 gliomas that have previously been treated with radiotherapy and chemotherapy at diagnosis or at first relapse. Contemporaneous tumour tissue at the time of first relapse, defined as tissue obtained within 6 months of relapse and without subsequent intervening therapy, will be obtained from patients. Molecular screening will be performed by targeted next-generation sequencing at the reference laboratory (PathWest, Perth, Australia). RNA and DNA will be extracted from representative formalin-fixed paraffin embedded tissue scrolls or microdissected from sections on glass slides tissue sections following a review of the histology by pathologists. Extracted nucleic acid will be quantified by Qubit Fluorometric Quantitation (Thermo Fisher Scientific). Library preparation and targeted capture will be performed using the TruSight Tumor 170 (TST170) kit and samples sequenced on NextSeq 550 (Illumina) using NextSeq V.2.5 hi output reagents, according to the manufacturer's instructions. Data analysis will be performed using the Illumina BaseSpace TST170 app v1.02 and a custom tertiary pipeline, implemented within the Clinical Genomics Workspace software platform from PierianDx (also refer to section 3.2). Primary outcomes for the study will be the number of patients enrolled and the number of patients who complete molecular screening. Secondary outcomes will include the proportion of screened patients enrolled; proportion of patients who complete molecular screening; the turn-around time of molecular screening; and the value of a brain tumour specific multi-disciplinary tumour board, called the molecular tumour advisory panel as measured by the proportion of patients in whom the treatment recommendation was refined compared with the recommendations from the automated bioinformatics platform of the reference laboratory testing. ETHICS AND DISSEMINATION: The study was approved by the lead Human Research Ethics Committee of the Sydney Local Health District: Protocol No. X19-0383. The study will be conducted in accordance with the principles of the Declaration of Helsinki 2013, guidelines for Good Clinical Practice and the National Health and Medical Research Council National Statement on Ethical Conduct in Human Research (2007, updated 2018 and as amended periodically). Results will be disseminated using a range of media channels including newsletters, social media, scientific conferences and peer-reviewed publications. TRIAL REGISTRATION NUMBER: ACTRN12620000087954; Pre-results.

The Founder's Lecture 2009: advances in imaging of osteoporosis and osteoarthritis.

The objective of this review article is to provide an update on new developments in imaging of osteoporosis and osteoarthritis over the past three decades. A literature review is presented that summarizes the highlights in the development of bone mineral density measurements, bone structure imaging, and vertebral fracture assessment in osteoporosis as well as MR-based semiquantitative assessment of osteoarthritis and quantitative cartilage matrix imaging. This review focuses on techniques that have impacted patient management and therapeutic decision making or that potentially will affect patient care in the near future. Results of pertinent studies are presented and used for illustration. In summary, novel developments have significantly impacted imaging of osteoporosis and osteoarthritis over the past three decades.

Evaluation of molecular analysis in challenging ovarian sex cord-stromal tumours: a review of 50 cases.

Molecular profiling was performed in 50 problematic ovarian sex cord-stromal tumours (SCSTs) most of which were seen in consultation. Following analysis, 17 were classified as adult granulosa cell tumour (AGCT), 16 of which showed a FOXL2 sequence variant (mutation); the initial favoured diagnosis in five of the cases was benign thecoma/fibrothecoma. Thirteen tumours ultimately classified as cellular fibroma or thecoma were FOXL2 sequence variant negative which was helpful in excluding AGCT. All six Sertoli-Leydig cell tumours (SLCTs) demonstrated DICER1 'hot spot' sequence variants, and one case each of AGCT and SLCT showed high grade histological transformation associated with a concurrent TP53 sequence variant. All eight unclassified SCSTs were negative for FOXL2 mutations and the six tested cases were DICER1 wild type; however, three tumours demonstrated MET, CTNNB1 or TP53 sequence variants. Four cases were classified as juvenile granulosa cell tumour, and one of these harboured a GNAS sequence variant. The single gynandroblastoma and microcystic stromal tumours in the series demonstrated FOXL2 and CTNNB1 alterations, respectively. In summary, molecular analysis aids in accurate classification of challenging ovarian SCSTs and sometimes leads to revision of the favoured provisional diagnosis. TP53 sequence variants may be associated with dedifferentiation in both SLCTs and AGCTs.

Fluoronavigation-assisted, lumbar vertebroplasty for a painful Schmorl node.

Lumbar Schmorl nodes usually remain asymptomatic. Painful nodes either heal spontaneously or respond to conservative therapy in most instances. Diagnosis and treatment may be difficult in patients presenting with chronic back pain. We present a 31-year-old man with a lumbar Schmorl node that was unrecognised for 10 years as the origin of his severe chronic back pain. Finally, MRI revealed a significant oedematous rim around a huge Schmorl node in the L4 vertebra. After conservative therapy failed the patient underwent a successful fluoronavigation-assisted, percutaneous vertebroplasty. In the absence of other pathological conditions, an oedematous rim around the node (as seen on MRI) is probably the pain generator in chronic back pain. We believe that the relevant nociceptors are located in the oedematous rim and not in the node itself. Therefore, cement augmentation of the rim is expected to be a successful treatment. Fluoronavigation facilitates safe access to the vertebral body.

Bryan cervical disc prostheses: preservation of function over time.

Preserving the function of cervical disc prostheses, even over the short term, is a matter of concern among surgeons. Our case series highlights our results and protocol for increasing the probability of continued device function. Twenty-five consecutive patients with a mean (+/-SEM) age of 44.3+/-8.3 years underwent 29 cervical total disc arthroplasties for disc herniations. Three patients underwent primary bilevel arthroplasty, and one patient underwent a second arthroplasty for another herniation 2 years after the first. Prosthesis ranges of motion were measured using dynamic plain X-ray studies and compared to the ranges of motion of adjacent segments. At follow-up, all prostheses were in the correct location and without subsidence. All displayed firm secondary stability. One segment had fused. Twenty-eight of 29 devices were mobile an average of 9.5 degrees +/-4.7 degrees (range 3 degrees to 20 degrees ) (for all 29 devices the average movement angle was 9.2 degrees +/-5 degrees ; range 0 degrees to 20 degrees ), 25 upper adjacent segments were mobile an average of 10.9 degrees +/-4.5 degrees (range 2 degrees to 20 degrees ) (excluding the fused prosthesis: 11 degrees +/-4.6 degrees ) and 15 lower adjacent segments were mobile an average of 9.8 degrees +/-6 degrees (range 1 degrees to 21 degrees ). With our protocol, 28 of 29 cervical disc prostheses in 25 consecutive patients were mobile after an average of 22.3+/-9.4 months. Prosthesis motion was physiological and very similar to that of the healthy adjacent segments. Long-term studies including larger numbers of patients are required to validate our initial observations.

Vertebroplasty combined with pedicular instrumentation.

Osteoporosis and cancer patients may suffer sudden severe back pain due to vertebral body osteolysis, microfractures and/or compression fractures. These patients need immediate restabilisation of the vertebral body to eliminate the pain generator, to prevent further crushing, and to reduce the comorbidity of prolonged immobilisation. Vertebroplasty combined with pedicular instrumentation is presented as a therapy for a selected group of such patients. Eight patients with an average age of 69.1 years experienced significant relief from disabling back pain. The ability to ambulate increased significantly. The risks associated with prolonged bed rest and hospital stay were reduced. There were only minor surgical complications. Follow-up was short because of the limited life expectancy of these severely ill patients. Disabling back pain was successfully treated and ongoing vertebral body collapse was prevented by vertebroplasty combined with pedicular instrumentation in the eight selected osteoporosis and cancer patients.

Sixteen-Year Experience of David and Bentall Procedures in Acute Type A Aortic Dissection.

BACKGROUND: To examine short-term and midterm outcomes after the David and Bentall procedures in patients with an acute type A aortic dissection. METHODS: Between 2001 and 2017, patients (n = 135) with acute type A aortic dissection underwent an aortic root replacement with either the David (n = 40) or Bentall (n = 95) procedure. Perioperative outcome, reoperation rate, aortic valve function, and long-term survival were evaluated. RESULTS: The median age of the entire cohort was 56 years. Rates of malperfusion (21%), shock (16%), history of renal failure (4%), and extent of surgery were similar between David and Bentall groups. However, the David group was significantly younger (45 versus 61 years) with less hypertension (45% versus 66%), coronary artery disease (0% versus 17%), valvulopathy (5% versus 19%), and prior cardiac surgery (5% versus 21%). Overall operative mortality was 9.6% (David 3% and Bentall 13%). Composite outcome comprising myocardial infarction, stroke, new-onset renal failure, and operative mortality was 18% in the entire cohort (David 5% and Bentall 23%). In the David group, the freedom of moderate aortic insufficiency was 95% at 10 years. The rate of reoperation for pathology of the proximal aorta or aortic valve was 0% and 2% for the David and Bentall groups, respectively. Ten-year Kaplan-Meier survival was 66% (95% confidence interval: 51% to 77%) for the entire cohort, with 98% (95% confidence interval: 84% to 99%) survival in the David group and 57% (95% confidence interval: 42% to 70%) survival in the Bentall group. CONCLUSIONS: Both the David and Bentall procedures are appropriate surgical approaches for aortic root replacement in select patients with an acute type A aortic dissection.

Intradural extramedullary arachnoid cyst of the thoracic spine associated with cord compression.

In this report, a 55-year-old Caucasian women with an arachnoid cyst of the thoracic spine is presented. This cyst remained undiagnosed because of the nonspecific nature of her symptoms over approximately three months. Only when she started to complain of ataxia, a posterior fluid collection compressing the spinal cord was found in MRI. Even though preoperative diagnosis remained uncertain, this additional neurological dysfunction warranted surgical treatment. Surgery was successful with respect to in-toto removal of the intradural, extramedullary cyst, reversal of cord compression and symptoms. Histological diagnosis was of an arachnoid cyst.