Proteombasierte diagnostische und prognostische Biomarker beim Prostatakarzinom

Background

Due to comprehensive PSA screening, the incidence for prostate cancer (PCa) is rising. Therefore, there is an urgent need for improved PCa diagnostics and prognostic tools to differentiate between insignificant and aggressive, fast growing tumors.

Methods

With the proteome-based method presented here, we were able to distinguish PCa from BPH, chronic prostatitis and healthy controls with 83?% sensitivity and 67?% specificity. Furthermore, the methods discerned advanced PCa from local, organ-confined PCa in a group of patients with gleason score 7 (80?% sensitivity, 82?% specificity).

Results

Our proteomic approach is based on the analysis of low molecular weight polypeptides, identified as the endpoint of the naturally occuring liquefaction cascade in seminal plasma. For the first time using seminal plasma as a source, we analysed a complex network of interacting proteases and specific inhibitors, reflecting tumor biology specificity. Our diagnostic and prognostic tool is robust and easy to handle, and therefore it is well suitable for the laboratory and medical practice.     

Subthalamic deep brain stimulation for refractory Gilles de la Tourette’s syndrome: clinical outcome and functional connectivity

Background

Deep brain stimulation (DBS) is a promising novel approach for managing refractory Gilles de la Tourette’s syndrome (GTS). The subthalamic nucleus (STN) is the most common DBS target for treating movement disorders, and smaller case studies have reported the efficacy of bilateral STN-DBS treatment for relieving tic symptoms. However, management of GTS and treatment mechanism of STN-DBS in GTS remain to be elucidated.

Methods

Ten patients undergoing STN-DBS were included. Tics severity was evaluated using the Yale Global Tic Severity Scale. The severities of comorbid psychiatric symptoms of obsessive–compulsive behavior (OCB), attention-deficit/hyperactivity disorder, anxiety, and depression; social and occupational functioning; and quality of life were assessed. Volumes of tissue activated were used as seed points for functional connectivity analysis performed using a control dataset.

Results

The overall tics severity significantly reduced, with 62.9% ± 26.2% and 58.8% ± 27.2% improvements at the 6- and 12-months follow-up, respectively. All three patients with comorbid OCB showed improvement in their OCB symptoms at both the follow-ups. STN-DBS treatment was reasonably well tolerated by the patients with GTS. The most commonly reported side effect was light dysarthria. The stimulation effect of STN-DBS might regulate these symptoms through functional connectivity with the thalamus, pallidum, substantia nigra pars reticulata, putamen, insula, and anterior cingulate cortices.

Conclusions

STN-DBS was associated with symptomatic improvement in severe and refractory GTS without significant adverse events. The STN is a promising DBS target by stimulating both sensorimotor and limbic subregions, and specific brain area doses affect treatment outcomes.

     

Groningen orthopaedic exit strategy: Validation of a support program after total hip or knee arthroplasty

OBJECTIVE: Validation of the program theory of the Groningen orthopaedic exit strategy (GOES), a theory-driven program aiming to improve the rehabilitation of total hip and knee arthroplasty patients after shortened hospital stay. First part of the program theory is the action theory, hypothesising that the GOES treatment positively influences the mediating variables (self-efficacy, social support, pain-coping). The second part, the conceptual theory, hypothesis a positive relationship between these variables and the outcome variables (ADL functioning, physical activity behaviour, quality of life). METHODS: Patients were randomly assigned to the GOES or control groups. Questionnaires were used to assess mediating and outcome variables in 103 patients (50 GOES, 53 controls) pre-operatively, and 6 and 26 weeks post-operatively. RESULTS: No difference was seen between the two groups in terms of changes between pre-operative and post-operative mediating variables (action theory). Moderate-to-large correlations explaining reasonable amount of variance (22%, 25%, 56%) were found between the mediating and outcome variables (conceptual theory). CONCLUSION: The conceptual theory is supported; however, as the treatment did not influence the mediating variables (action theory), it has no added value in its current form. PRACTICE IMPLICATIONS: The treatment needs to be adjusted; it is discussed that individualised treatment could be more effective.     

Bioinformatic integration of biomechanics makes HLA sequencing universally applicable

Sequencing provides the most reliable and accurate information of the sequence of a gene and is therefore of particular interest for fully characterizing the genetic complexity and allelic diversity of human leukocyte antigens (HLA) genes. This complexity makes sequencing the method of choice for HLA low- and high-resolution typing. However, sequencing is considered a complex process, which requires the management of an overwhelming amount of data. However, only sequencing can be used as a sole typing technique without the need of supplementation by other typing techniques; it offers additional advantages by providing results in electronic formats and by being fully automatable. This makes sequencing the best candidate for bioinformatic and biomechanic integration to maintain the benefits and discard the drawbacks. We have, therefore, developed robotic platforms and a bioinformatic tool allowing complete documentation, interpretation and processing of all amplification and sequencing steps as well as the full integration of all instruments involved. It was shown that this integrative approach allows sequencing to run fully automated for low- and high-resolution typing on each throughput level desired. This integration of robotics and software secures the traceability of each specimen at each step of the process and minimizes the risk of contamination and sample mix-up.     

In vitro assessment of motility and proliferation of human osteogenic cells on different isolated extracellular matrix components compared with enamel matrix derivative by continuous single-cell observation

OBJECTIVES: The composition of the extracellular matrix (ECM) plays a substantial role in bone remodelling, fracture healing and osseointegration of dental implants by regulating proliferation, migration and finally differentiation of osteogenic cell populations. Emdogain, a composition of an enamel matrix derivative (EMD), has been introduced as a potential candidate to promote tissue regeneration. We investigated whether EMD could serve as a potential promoter of cell proliferation and motility as a dynamic cell response and compared the results with the ubiquitous single ECM components type I collagen and laminin. MATERIAL AND METHODS: In the investigation presented, we used a continuous observation method for the analysis of migratory and proliferative patterns of individual cells. We analyzed the response of four osteoblastic cell lines to specific extracellular ligands (type I collagen, laminin and EMD) over a period of 24 h compared with untreated glass surface and bovine serum albumin (BSA) as control groups. RESULTS: Type I collagen and laminin promoted cell motility significantly compared with the control groups and, in part, compared with EMD as well. The analysis of all 451 investigated cells revealed the following mean values for cell motiliy: untreated glass (n=99): 5.46+/-2.74 microm/h, BSA (n=89): 6.35+/-2.43 microm/h, type I collagen (n=108): 8.77+/-3.42 microm/h, laminin (n=74): 9.89+/-5.10 microm/h and EMD (n=81): 7.92+/-3.35 microm/h. Proliferation rates on the different surfaces were heterogenous for all investigated cell lines and varied from 0% to 50% within 24 h without a correlation to cell motility. CONCLUSION: In our study, EMD promotes cell motility better than the control groups. The two investigated single ECM components type I collagen and laminin promoted cell motility superior to EMD. This supports the hypothesis that EMD promotes a less mobile but more differentiated osteogenic phenotype.     

Postautologous stem cell transplantation engraftment syndrome: Improved treatment and outcomes

Postautologous stem cell transplantation (ASCT) engraftment syndrome (ES) is a well-known clinical complication; however, many aspects remain largely controversial. In this retrospective study, we reviewed records of 156 ASCTs done over 2 years in our institution. Our results show that 45 (34 multiple myeloma/amyloidosis and 11 lymphoma) of 156 adult patients (29%) were diagnosed with ES. Patients with ES were significantly more likely to have fever, rash, and diarrhea upon engraftment. Risk factors for ES included shorter time from diagnosis to ASCT (P = .029), and lower number of pretransplant treatment regimens (0.012). Post-ASCT, patients with ES had significantly lower absolute lymphocyte count on first engraftment day (P = .014). Most ES patients received treatment with steroids. Initial dose of prednisone/methylprednisolone was 2 mg/kg (n = 34), 1 mg/kg (n = 7), while four patients received 1000 mg IV with median length of therapy 7.5 days. One ES patient with inadequate steroid therapy died of ES complications, while another developed respiratory failure requiring intubation but had full recovery with steroids treatment. In conclusion, patients with shorter time from diagnosis to ASCT and with less prior therapy are more likely to develop ES. Overall survival of ES patients has improved with greater awareness of the diagnosis and earlier use of steroids.