Search

Background and importance The amount of subarachnoid blood and the presence of toxic blood breakdown products in the cerebrospinal fluid (CSF) have long been associated with poor outcomes in aneurysmal subarachnoid hemorrhage. The Neurapheresis™ system (Minnetronix Inc, St. Paul, Minnesota) has been developed to filter CSF and remove blood products, and is being investigated for safety and feasibility in the ExtracorPoreal FILtration of subarachnoid hemorrhage via SpinaL CAtheteR (PILLAR) study. We report the first case using this novel device. Clinical presentation A 65-yr-old female presented with a ruptured left posterior communicating artery aneurysm. Following placement of a ventriculostomy and coil embolization of her aneurysm, the patient underwent placement of a lumbar dual lumen catheter for CSF filtration as part of the PILLAR study. In this case, a total of 9 h of filtration during 31 h of catheter indwelling resulted in 309.47 mL of processed CSF without complication. Computed tomography images demonstrated an interval reduction of subarachnoid hemorrhage immediately after filtration. The patient was discharged home on postbleed day 11 and at 30 d showed good recovery. Conclusion Safety of the Neurapheresis procedure was confirmed in this first case, and we will continue to evaluate safety of the Neurapheresis system through the PILLAR trial.

Fragestellung: Ziel der Arbeit war es, die Fähigkeiten des Storz Professional Image Enhancement Systems (SPIES) und der Photodynamischen Diagnostik (PDD) im Vergleich zur Weißlicht-Zystoskopie (WLC) zu untersuchen, die verpassten Diagnosen von Blasenkarzinomen (BCa) unabhängig von der[zum vollständigen Text gelangen Sie über die oben angegebene URL], 43. Gemeinsame Tagung der Österreichischen Gesellschaft für Urologie und Andrologie und der Bayerischen Urologenvereinigung

Background: Shorter telomere length (TL) has been reported to be associated with increased risk of early death in elder individuals. Telomere shortening has been also related to chromosomal instability, which may possibly contribute to the development of several types of digestive or urogenital system cancers and smoking-related tumors. Therefore, we investigated the impact of TL on bladder cancer survival. Methods: TL was measured in leukocyte DNA from whole peripheral blood using quantitative real-time PCR in 463 patients with bladder cancer from a total 726 cases who were followed for up to 18 years. Results: Patients with muscle-invasive tumor/any grade had shorter telomere than patients with non–muscle-invasive tumor/high-grade and with non–muscle-invasive tumor/non–high-grade (TL reference 0.7 ± 0.2; vs. respectively, 0.8 ± 0.2, P = 3.4 × 10−2 and 0.8 ± 0.2, P = 3.6 × 10−2). Moreover, patients in the lowest quartiles of TL were associated with decreased survival after diagnosis (log-rank test, P = 3.9 × 10−4). A Cox regression adjusted by age, cancer aggressiveness, Bacillus Calmette-Guérin, radical cystectomy, radiotherapy, and chemotherapy showed an independent effect of TL on bladder cancer survival (HR, 3.9; 95% confidence interval, 1.7–9.1; P = 1.2 × 10−3). Conclusions: Our results suggest that leukocyte TL is only partly related to tumor aggressiveness and that shorter telomeres act as independent prognostic predictor of survival in patients with bladder cancer. TL information may allow to better select therapeutic approaches in patients with the same stage and grade. Impact: Blood leukocyte TL levels could provide an additional noninvasive prognostic marker to better predict survival and personalize therapies in patients with bladder cancer. Cancer Epidemiol Biomarkers Prev; 23(11); 2439–46. ©2014 AACR.

[FeFe]-hydrogenases are the enzymes responsible for high yield H 2 production during dark fermentation in bio-hydrogen production plants. The culturable bacterial population present in a pilot-scale plant efficiently producing H2 from waste materials was isolated, classified and identified by means of 16S rDNA gene analysis. The culturable part of the mixed population consists of nine bacterial species that include non-hydrogen producers (Lactobacillus, Enterococcus and Staphylococcus) and several Clostridium that are directly responsible for H2 production. An extensive analysis of the expression of [FeFe]-hydrogenases in the three best producer strains was achieved by RT-PCR, covering the complete set of known genes for each species. This revealed that during H2 production there are several different [FeFe]-hydrogenases simultaneously expressed, with genes belonging to the same phylogenetic and structural classification sharing similar transcriptional profiles. © 2014, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.

Objective To assess the response rate to different erectile aids in a consecutive series of patients treated with non-nerve sparing radical prostatectomy (NNSRP). Patients and Methods Ninety-four potent men were counselled about the different treatment options to restore an assisted erection before they had NNSRP. They were invited to participate in a multiphase protocol involving the sequential use of different erectile aids which aimed at restoring erectile function after surgery. The first proposed treatment was oral apomorphine sublingual. Patients with a positive response to the 1-item overall efficacy question and a minimum score of 3 in both question 3 and 4 of the International Index of Erectile Function were considered responders to oral pharmacotherapy. Treatment with sildenafil was then suggested to those not responding. If patients did not respond to oral pharmacotherapy a trial with a vacuum erectile device was offered; those not responding to this were then offered intracavernosal injection therapy with prostaglandin-E alone as the first option, followed by a mixture of vasoactive agents if needed. In those in whom injections also failed, a penile implant was recommended. At the 1-year follow-up visit all patients were offered a second trial with oral therapy regardless of the treatment currently in use. Results Seventy-six patients entered the protocol; there was no response to apomorphine. Five of 59 (8%) patients responded to sildenafil when they first used it at a mean of 7 months after NNSRP, while there were three additional responders in 22 patients who tried it for a second time a year later. Of patients achieving at least a complete tumescence sufficient for vaginal penetration, 52% and 60% were considered responders to the vacuum device and intracavernosal injections, respectively. Overall, 44% of patients enrolled in the protocol chose to use an erectile aid for at-home use. At the 1-year follow-up, only 20% of patients were still using an erectile aid, including two who had had a penile implant. Conclusions Up to 10% of patients may achieve a clinically significant erection with sildenafil after NNSRP, but 80% will not be using any erectile aid at 1 year after surgery. In the present study protocol the proposed erectile aids were largely inadequate for treating the permanent erectile dysfunction that follows NNSRP.

Objective: To determine the impact of prognostic factors of a series of high-grade Ta non-muscle-invasive bladder cancers (NMIBCs) according to the new International Society of Urological Pathology (ISUP) 1998/WHO 2004 grading system (previously classified as either TaG2 or TaG3). Methods: One hundred and thirty-one high-grade Ta (105 G2 and 26 G3) cases were identified after independent review by two pathologists. Univariable and multivariable Cox regression models addressed recurrence and progression-free survival. Progression was defined as appearance of any T ≥1 recurrence after complete TUR (type 1) or occurrence of T ≥2 (type 2). Results: Ten-year recurrence, type-1 and type-2 progression-free survival were 60, 75 and 95%, respectively. The previous grading system (G3 vs. G2) significantly predicted type 1 progression in the univariate model only. In the multivariate model, Ki67 was the only independent predictor of progression according to both definitions (HR = 5.25, p = 0.002 and HR = 6.16, p = 0.03, respectively). Conclusions: High-grade Ta NMIBC as defined by the WHO 2004 grading system cannot be equated with high-risk NMIBC. The risk of progression to muscle-invasive disease (type 2) is low, more in keeping with an intermediate-risk category of NMIBC. The previous WHO 1973 subcategorization into G2 and G3 is of little help in the prediction of outcome. Ki67 is a strong independent predictor of progression worthy of consideration for a clinical setting.

Survival of bladder cancer patients depends on several factors including disease stage and grade at diagnosis, age, health status of the patient and the applied treatment. Several studies investigated the role of DNA repair genetic variants in cancer susceptibility, but only few studies investigated their role in survival and response to chemotherapy for bladder cancer. We genotyped 28 single nucleotide polymorphisms (SNP) in DNA repair genes in 456 bladder cancer patients, reconstructed haplotypes and calculated a score for combinations of the SNPs. We estimated Hazard Ratios (adjHR) for time to death. Among patients treated with chemotherapy, variant alleles of five SNPs in the XRCC1 gene conferred better survival (rs915927 adjHR 0.55 (95%CI 0.32–0.94); rs76507 adjHR 0.48 (95%CI 0.27–0.84); rs2854501 adjHR 0.25 (95%CI 0.12–0.52); rs2854509 adjHR 0.21 (95%CI 0.09–0.46); rs3213255 adjHR 0.46 (95%CI 0.26–0.80). In this group of patients, an increasing number of variant alleles in a XRCC1 gene score were associated with a better survival (26% decrease of risk of death for each additional variant allele in XRCC1). By functional analyses we demonstrated that the previous XRCC1 SNPs confer lower DNA repair capacity. This may support the hypothesis that survival in these patients may be modulated by the different DNA repair capacity determined by genetic variants. Chemotherapy treated cancer patients bearing an increasing number of “risky” alleles in XRCC1 gene had a better survival, suggesting that a proficient DNA repair may result in resistance to therapy and shorter survival. This finding may have clinical implications for the choice of therapy.

Precise neurosurgical targeting of electrode arrays within the brain is essential to the successful treatment of a range of brain disorders with deep brain stimulation (DBS) therapy. Here, we describe a set of computational tools to generate in vivo, subject-specific atlases of individual thalamic nuclei thus improving the ability to visualize thalamic targets for preclinical DBS applications on a subject-specific basis. A sequential nonlinear atlas warping technique and a Bayesian estimation technique for probabilistic crossing fiber tractography were applied to high field (7T) susceptibility-weighted and diffusion-weighted imaging, respectively, in seven rhesus macaques. Image contrast, including contrast within thalamus from the susceptibility-weighted images, informed the atlas warping process and guided the seed point placement for fiber tractography. The susceptibility-weighted imaging resulted in relative hyperintensity of the intralaminar nuclei and relative hypointensity in the medial dorsal nucleus, pulvinar, and the medial/ventral border of the ventral posterior nuclei, providing context to demarcate borders of the ventral nuclei of thalamus, which are often targeted for DBS applications. Additionally, ascending fiber tractography of the medial lemniscus, superior cerebellar peduncle, and pallidofugal pathways into thalamus provided structural demarcation of the ventral nuclei of thalamus. The thalamic substructure boundaries were validated through in vivo electrophysiological recordings and post-mortem blockface tissue sectioning. Together, these imaging tools for visualizing and segmenting thalamus have the potential to improve the neurosurgical targeting of DBS implants and enhance the selection of stimulation settings through more accurate computational models of DBS.

Deep brain stimulation (DBS) leads with radially distributed electrodes have potential to improve clinical outcomes through more selective targeting of pathways and networks within the brain. However, increasing the number of electrodes on clinical DBS leads by replacing conventional cylindrical shell electrodes with radially distributed electrodes raises practical design and stimulation programming challenges. We used computational modeling to investigate: (1) how the number of radial electrodes impact the ability to steer, shift, and sculpt a region of neural activation (RoA), and (2) which RoA features are best used in combination with machine learning classifiers to predict programming settings to target a particular area near the lead. Stimulation configurations were modeled using 27 lead designs with one to nine radially distributed electrodes. The computational modeling framework consisted of a three-dimensional finite element tissue conductance model in combination with a multi-compartment biophysical axon model. For each lead design, two-dimensional threshold-dependent RoAs were calculated from the computational modeling results. The models showed more radial electrodes enabled finer resolution RoA steering; however, stimulation amplitude, and therefore spatial extent of the RoA, was limited by charge injection and charge storage capacity constraints due to the small electrode surface area for leads with more than four radially distributed electrodes. RoA shifting resolution was improved by the addition of radial electrodes when using uniform multi-cathode stimulation, but non-uniform multi-cathode stimulation produced equivalent or better resolution shifting without increasing the number of radial electrodes. Robust machine learning classification of 15 monopolar stimulation configurations was achieved using as few as three geometric features describing a RoA. The results of this study indicate that, for a clinical-scale DBS lead, more than four radial electrodes minimally improved in the ability to steer, shift, and sculpt axonal activation around a DBS lead and a simple feature set consisting of the RoA center of mass and orientation enabled robust machine learning classification. These results provide important design constraints for future development of high-density DBS arrays.

Questo lavoro analizza gli effetti del segreto sul funzionamento familiare e le conseguenze che questo comporta, sia sul piano coniugale che genitoriale. Si analizzerŕ la connessione tra segreto e mito familiare e gli aspetti legati alle loro funzioni protettive e difensive dell'identitŕ dei membri della famiglia. Sul piano coniugale e genitoriale saranno presentate delle ipotesi sull'influenza del segreto nella definizione della relazione tra gli individui e sulla natura patogena di tale stile relazionale familiare. Sarŕ trattata, infine, la figura del terapeuta, sia come fattore di cambiamento rispetto allo svelamento del segreto in terapia che come aiuto alla famiglia nel connettere il suo "tempo".

A paraitre; International audience; Dans cet article nous présentons le projet LyText (Lycée + Texte), un environnement informatique d'aide à la préparation du baccalauréat de français, développé par l'ATILF et en concertation étroite avec les enseignants grâce au soutien de l'Académie et de la Région Lorraine. Après une présentation générale de LyText, ses objectifs, sa philosophie générale, les connaissances mises en oeuvre et un aperçu de la méthodologie suivie pour instancier un texte au sein de LyText, nous ferons un premier bilan de ses apports tant à l'enseignant pour l'accompagner dans ses objectifs pédagogiques qu'au lycéen comme support de travail personnel. Nous terminerons enfin en présentant les perspectives futures d'évolution de ce système.

This paper deals with the experimental analysis of the performance and degradation issues of a Ni-based anode-supported solid oxide fuel cell fed by a methane-free biogas from dark-anaerobic digestion of wastes by pastry and fruit shops. The biogas is produced by means of an innovative process where the biomass is fermented with a pre-treated bacteria inoculum (Clostridia) able to completely inhibit the methanization step during the fermentation process and to produce a H2/CO2 mixture instead of conventional CH4/CO2 anaerobic digested gas (bio-methane). The proposed biogas production route leads to a biogas composition which avoids the need of introducing a reformer agent into or before the SOFC anode in order to reformate it. In order to analyse the complete behaviour of a SOFC with the bio-hydrogen fuel, an experimental session with several H2/CO2 synthetic mixtures was performed on an anode-supported solid oxide fuel cell with a Ni-based anode. It was found that side reactions occur with such mixtures in the typical thermodynamic conditions of SOFCs (650–800 °C), which have an effect especially at high currents, due to the shift to a mixture consisting of hydrogen, carbon monoxide, carbon dioxide and water. However, cells operated with acceptable performance and carbon deposits (typical of a traditional hydrocarbon-containing biogas) were avoided after 50 h of cell operation even at 650 °C. Experiments were also performed with traditional bio-methane from anaerobic digestion with 60/40 vol% of composition. It was found that the cell performance dropped after few hours of operation due to the formation of carbon deposits. A short-term test with the real as-produced biogas was also successfully performed. The cell showed an acceptable power output (at 800 °C, 0.35 W cm−2 with biogas, versus 0.55 W cm−2 with H2) although a huge quantity of sulphur was present in the feeding fuel (hydrogen sulphide at 103 ppm and mercaptans up to 10 ppm). Therefore, it was demonstrated the interest relying on a sustainable biomass processing which produces a biogas which can be directly fed to SOFC using traditional anode materials and avoiding the reformer component since the methane-free mixture is already safe for carbon deposition.

This review aims to provide information about quality of life in elderly patients who have undergone radical cystectomy and bladder replacement for muscle-invasive bladder cancer, focusing on the best instruments for evaluation. Among patients over 75 years of age, bladder cancer is the fifth leading cause of death. Radical cystectomy is the standard treatment for muscle-invasive bladder cancer and it is also considered safe in the elderly population. Quality of life is an essential aspect following radical cystectomy and bladder replacement owing to its impact on patients’ satisfaction with body image and urinary, sexual and social functioning. Furthermore, the authors suggest that there are no significant differences between different methods of urinary diversion in the elderly.

Neuroendocrine bladder cancer is extremely rare, with an estimated incidence of 0.5%- 0.7%. In bladder cancers there is no evident connection between the neuroendocrine phenotypic expression and the clinical history. However, prognosis is usually poor and the survival rate at 5 years does not exceed 8%, if untreated. Methods. We are here describing three case reports of bladder carcinoma with neuroendocrine differentiation, which is extremely aggressive and leads rapidly to death. At the present time, the local control of these tumors is achieved by radical cystectomy and radiotherapy; they can be both associated to chemotherapy. However, since these lesions are fairly rare, there is no gold standard therapy and there are no prospective studies on the management of these tumors. Conclusions. Considering the quick evolution and progression of any variant of the neuroendocrine tumors of the bladder, urologists and anesthetists should see them as real oncological emergencies. A prompt intervention through radical surgery with cystectomy and linfadenectomia, and the anathomo-pathologist's systematic investigation of the scraps could make the approach therapeutic and not only palliative. Prospective studies on neo-adjuvant chemotherapy as well as experimental studies about target therapies may yield new guidelines on the tumor management.

Objective: Targeted fusion biopsies have led to an improved prostate cancer (PCa) detection rate (CDR). Our aim was to assess if device-assisted fusion biopsies are superior to cognitive ones in terms of CDR. The association between multiparametric MRI parameters and PCa was also evaluated. Methods: We retrospectively enrolled 50 patients who underwent transrectal biopsy with elastic fusion (Koelis; group KB, n = 25) or cognitive approach (group CB, n = 25). Targeted biopsies were done on targets, while a variable number of random biopsies were performed depending on the clinical case. Results: The groups did not significantly differ in terms of age, prostate-specific antigen, prostate volume and previous biopsies. Mean number of random cores was significantly inferior in KB group (8.4 vs. 12.1) and mean number of targeted biopsies was significantly higher (3.6 vs. 2.6). CDR was higher in fusion biopsies (64 vs. 40%), with the gap becoming significant when considering CDR of MRI targets only (59 vs. 27%). The difference was marked for lesions ≤10 mm, where CDR was 52% in KB against 21% in CB group. Conclusions: According to our study, elastic fusion biopsies performed with Koelis achieve an increased per-patient and per-lesion CDR as compared to cognitive biopsies, especially in the case of lesions ≤10 mm.

A paraneoplastic syndrome is a clinical condition in a patient affected by tumor which occurs distally from the primary neoplasia or its metastases, and is assessed via the humoral mediators. The uncommon secretion of peptide hormones is the most frequent cause of paraneoplastic syndromes. Although the symptoms are strongly varied, paraneoplastic endocrine syndromes are characterized by several functional features that differentiate them from the endocrine glands hyper-function related disorders. Based on the field's literature, the article presents the pathogenetic mechanisms, the laboratory and imaging features, and the essential therapeutic measures for humoral hypercalcemia of malignancy, hypercortisolism from ectopic ACTH/CRH production and water intoxication syndrome due to inadequate ADH secretion. Moreover, neuroendocrine differentiation in some urogenital cancers (prostate, bladder, kidney etc.), occurring as pure endocrine malignancy or as focal lesion, can develop a paraneoplastic carcinoid-like syndrome. On the other hand, some patients with urogenital tumors have increased serum levels of IGF-2 resulting in paraneoplastic hypoglycemia.

Colorectal cancer is one of the most common cancers affecting men and women in the United States. In 2005, 10% of all new cancer cases in men will be colorectal; for women, 11% of new cases will be colorectal. The disease is the third most frequent cancer occurring in both sexes. Colorectal cancer also is the third most frequent cause of death for men and women, and more than 56,000 cancer deaths in 2005 will be attributed to colorectal cancer. Chemotherapy options for treatment of the disease remained relatively stagnant until the approval of irinotecan in 1996 followed by capecitabine, oxaliplatin, and the new targeted agents. The new agents have improved efficacy of treatment for colorectal cancer and the lives of patients with advanced disease. With the new options for treatment come increased nursing and patient-teaching responsibilities, as well as increased costs associated with the newer drugs in the armamentarium of chemotherapy agents. Formulary budgets are seeing dramatic rises in expenditures for the new, targeted therapy treatments; discussion of the most appropriate therapies may be considered. This article will discuss epidemiology of colorectal cancer, treatment options in advanced colorectal cancer, and nursing care crucial to patients undergoing chemotherapy. Discussion of economic impact also will be presented.

Background The World Health Organization has identified Pseudomonas, Acinetobacter and Klebsiella (PAK) as three multidrug resistant (MDR) gram-negative pathogens that pose a threat to human health. The greatest threat lies in hospitals, nursing homes, and patients with devices such as intravenous catheters and ventilators. Gram-negative bacterial meningitis (GBM) manifests when these bacteria invade the central nervous system. Due to the threat of increasing antibiotic resistance and the high mortality associated with MDR GBM, we have tested a closed-loop, extracorporeal cerebrospinal fluid (CSF) filtration system (NeurapheresisTM) for its applicability in this context. Here we demonstrate feasibility of Neurapheresis for MDR GBM and characterize system parameters for bacterial clearance. Methods PAK cultures were grown and diluted to 1 × 107 cells/mL in artificial CSF or Luria-Miller broth. Both single pass and closed loop filtration were performed with various tangential flow filtration (TFF) and dead-end filter paradigms. Samples were taken either immediately post-filter or after every full CSF volume cycle (150 mL) during a long-term closed loop experiment. Bacterial load, endotoxin and cytokines were quantified. Results In single pass tests, 5kDa and 100kDa TFF filters and 0.2µm and 0.45µm dead-end filters excluded all PAK organisms completely. The 100kDa and 5kDa TFF filters significantly reduced endotoxin concentration by >95% and >99% of baseline, respectively. The 5 kDa TFF filters produced a 2-log (>99%) reduction in cytokines (IL-1ra, IL-6, TNF, CRP, and CXCL10). In closed-loop experiments, both TFF filters demonstrated a 1–2 Log CFU (90–99%) reduction of all PAK organisms over 4 filtration cycles. Conclusion Neurapheresis shows potential to be an efficient multi-modal tool for controlling and treating MDR GBM in this in vitro model. Extending closed loop filtration over time demonstrates capability for rapid sterilization of the CSF. Future iterations may include adjunctive intrathecal drug delivery to further accelerate elimination of bacteria. Reduction of both endotoxin and cytokines by Neurapheresis may have significant implications for controlling the damaging neuro-inflammatory response during MDR GBM. Disclosures B. Hedstrom, Minnetronix, Inc.: Employee, Salary; L. Zitella Verbick, Minnetronix, Inc.: Employee, Salary; A. Mccabe, Minnetronix, Inc.: Employee, Salary; S. P. Lad, Minnetronix, Inc.: Collaborator and Scientific Advisor, Licensing agreement or royalty, Research grant and Research support; V. Fowler Jr., Pfizer, Novartis, Galderma, Novadigm, Durata, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., Cerexa, Tetraphase, Trius, MedImmune, Bayer, Theravance, Cubist, Basilea, Affinergy, Janssen, xBiotech, Contrafect: Consultant, Consulting fee; NIH, MedImmune, Cerexa/Forest/Actavis/Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Cubist/Merck; Medical Biosurfaces; Locus; Affinergy; Contrafect; Karius: Grant Investigator, Grant recipient; Green Cross, Cubist, Cerexa, Durata, Theravance; Debiopharm: Consultant, Consulting fee; UpToDate: Royalties, Royalties