DeepCME: A deep learning framework for computing solution statistics of the chemical master equation.

Stochastic models of biomolecular reaction networks are commonly employed in systems and synthetic biology to study the effects of stochastic fluctuations emanating from reactions involving species with low copy-numbers. For such models, the Kolmogorov's forward equation is called the chemical master equation (CME), and it is a fundamental system of linear ordinary differential equations (ODEs) that describes the evolution of the probability distribution of the random state-vector representing the copy-numbers of all the reacting species. The size of this system is given by the number of states that are accessible by the chemical system, and for most examples of interest this number is either very large or infinite. Moreover, approximations that reduce the size of the system by retaining only a finite number of important chemical states (e.g. those with non-negligible probability) result in high-dimensional ODE systems, even when the number of reacting species is small. Consequently, accurate numerical solution of the CME is very challenging, despite the linear nature of the underlying ODEs. One often resorts to estimating the solutions via computationally intensive stochastic simulations. The goal of the present paper is to develop a novel deep-learning approach for computing solution statistics of high-dimensional CMEs by reformulating the stochastic dynamics using Kolmogorov's backward equation. The proposed method leverages superior approximation properties of Deep Neural Networks (DNNs) to reliably estimate expectations under the CME solution for several user-defined functions of the state-vector. This method is algorithmically based on reinforcement learning and it only requires a moderate number of stochastic simulations (in comparison to typical simulation-based approaches) to train the "policy function". This allows not just the numerical approximation of various expectations for the CME solution but also of its sensitivities with respect to all the reaction network parameters (e.g. rate constants). We provide four examples to illustrate our methodology and provide several directions for future research.

Comparing efficacy and side effects of two systemic chemotherapy regimens for eye-preserving therapy in children with retinoblastoma.

BACKGROUND: Eye-preserving therapy in retinoblastoma comprises systemic chemotherapy, but studies analyzing the efficacy of different chemotherapy regimens are scarce. METHODS: The efficacy and side effects of two different eye-preserving chemotherapy regimens containing either vincristine, etoposide, and carboplatin (VEC) or cyclophosphamide, vincristine, etoposide, and carboplatin (CyVEC) were compared in a prospective non-interventional observational study including children diagnosed with retinoblastoma between 2013 and 2019 in Germany and Austria. Event-free eye survival (EFES) and overall eye survival (OES) of all 164 eyes treated with both regimens and risk factors were investigated. RESULTS: The EFES after VEC (2-year EFES 72.3%) was higher than after CyVEC (2-year EFES 50.4%) (plogrank  < .001). The OES did not differ significantly between the two treatment groups (plogrank  = .77; 2-year OES VEC: 82.1% vs. CyVEC: 84.8%). Advanced International Classification of Retinoblastoma (ICRB) group was prognostic for a lower EFES (plogrank  < .0001; 2-year EFES ICRB A/B/C 71.3% vs. ICRB D/E 43.0%) and OES (plogrank  < .0001; 2-year OES ICRB A/B/C 93.1% vs. ICRB D/E 61.5%). The multivariate analysis showed that age at diagnosis older than 12 months and ICRB A/B/C were associated with better EFES. No second malignancies or ototoxicities were reported after a follow-up of median 3.1 years after diagnosis of retinoblastoma (range 0.1-6.9 years). CONCLUSIONS: Despite omitting cyclophosphamide, the EFES was higher after VEC chemotherapy that contains higher doses of carboplatin compared to CyVEC. The major risk factor for enucleation was advanced ICRB tumor grouping. Randomized clinical trials on efficacy and side effects of eye-preserving chemotherapy are required to tailor treatment protocols for retinoblastoma patients.

Cotinine and cytokine levels in the vitreous body and blood serum of smokers and non-smokers - A pilot study.

Tobacco smoking is a risk factor for many ocular diseases. Of the multiple tobacco smoke compounds nicotine and its main metabolite cotinine are likely agents in disease modulation. The interaction of these compounds with exposed tissue is complex and ranges from proinflammatory to potentially neuroprotective properties. We aimed to determine cotinine and cytokines in the vitreous in smokers and non-smokers in this prospective, cross-sectional study at the Department of Ophthalmology, Medical University Graz, Austria. We included 10 smokers and 10 non-smokers. Vitreous and serum samples were analyzed for cotinine and cytokines. The cytokine analysis was performed with multiplex assay and cotinine was quantified with enzyme-linked immunosorbent assay. Cotinine was detectable in smokers only with a mean of 154.0 ng/ml ± 107.3 ng/ml in the vitreous and of 194.1 ng/ml ± 121.3 ng/ml in the serum. The difference between intraocular and systemic levels was statistically significant. There were no statistically significant differences between the cytokine levels of smokers and non-smokers. However, intravitreal VEGF-A was by trend elevated in smokers and correlated positively with intravitreal cotinine (r = 0.59, p = 0.073). In conclusion cotinine is detectable in the vitreous of smokers and is lower than the serum. There is a trend towards elevation of VEGF-A in the vitreous of smokers.

Long-term oncological and functional follow-up in low-dose-rate brachytherapy for prostate cancer: results from the prospective nationwide Swiss registry.

OBJECTIVE: To evaluate the long-term oncological, functional and toxicity outcomes of low-dose-rate brachytherapy (LDR-BT) in relation to risk factors and radiation dose in a prospective multicentre cohort. PATIENTS AND METHODS: Data of patients from 12 Swiss centres undergoing LDR-BT from September 2004 to March 2018 were prospectively collected. Patients with a follow-up of ≥3 months were analysed. Functional and oncological outcomes were assessed at ~6 weeks, 6 and 12 months after implantation and annually thereafter. LDR-BT was performed with 125 I seeds. Dosimetry was done 6 weeks after implantation based on the European Society for Radiotherapy and Oncology recommendations. The Kaplan-Meier method was used for biochemical recurrence-free survival (BRFS). A prostate-specific antigen (PSA) rise above the PSA nadir + 2 was defined as biochemical failure. Functional outcomes were assessed by urodynamic measurement parameters and questionnaires. RESULTS: Of 1580 patients in the database, 1291 (81.7%) were evaluable for therapy outcome. The median (range) follow-up was 37.1 (3.0-141.6) months. Better BRFS was found for Gleason score ≤3+4 (P = 0.03, log-rank test) and initial PSA level of <10 ng/mL (P < 0.001). D'Amico Risk groups were significantly associated with BRFS (P < 0.001), with a hazard ratio of 2.38 for intermediate- and high-risk patients vs low-risk patients. The radiation dose covering 90% of the prostate volume (D90) after 6 weeks was significantly lower in patients with recurrence. Functional outcomes returned close to baseline levels after 2-3 years. A major limitation of these findings is a substantial loss to follow-up. CONCLUSION: Our results are in line with other studies showing that LDR-BT is associated with good oncological outcomes together with good functional results.

Vitreous albumin redox state in open-angle glaucoma patients and controls: a pilot study.

PURPOSE: Numerous studies suggest that reactive oxygen species play a crucial role in the development of glaucoma. Since glaucoma patients exhibit posterior vitreous detachment earlier than controls, it has been suggested that reactive oxygen species-increased in glaucoma-also affect the vitreous. In the present study we evaluated the influence of open-angle glaucoma oxidative stress on the redox state of vitreous albumin. METHODS: Albumin redox states of the vitreous and plasma were evaluated in 22 subjects-11 open-angle glaucoma patients and 11 controls-matched for age, gender, and vitreous state. According to the redox state of cysteine-34, albumin can be separated into: human mercaptalbumin (the thiol form), human nonmercaptalbumin1 (a reversible modification due to mild oxidation), and human nonmercaptalbumin2 (an irreversible modification due to severe oxidation). RESULTS: Albumin of both, the open-angle glaucoma group and the control group, was more oxidized in the vitreous compared to plasma. Furthermore, significantly higher human nonmercaptalbumin1 fractions were found in the vitreous of open-angle glaucoma patients compared to controls. No significant differences were found in the plasma albumin fractions between the groups. CONCLUSION: Our results support the hypothesis that oxidative stress plays a crucial role in open-angle glaucoma and that reactive oxygen species in glaucomatous eyes may also affect the vitreous.

A Unifying Concept of Uveal Pigment Cell Distribution and Dissemination Based on an Animal Model: Insights into Ocular Melanogenesis.

Pigmented cells are derived from neural crest cells, which migrate along the peripheral nerve sheets into their specific final region. During their migration, cells progressively acquire pigment-producing capabilities, maturation, and the shape of melanocytes. These insights, along with specific clinical characteristics of melanocytic nevi, have led to new concepts of cutaneous, periocular, and iris nevogenesis. To further elucidate the specific ocular embryogenic melanoblast distribution and dissemination - that could explain the distinct distribution of uveal melanocytic neoplasms - we investigated the ocular pigmentation of dogs affected by a specific mutation called Merle, which results in either pigment- (wild type) or non-pigment- (mutated type) producing cells. Based on our observations, we propose a unifying concept of uveal pigment cell distribution and dissemination, which postulates melanoblast migration and maturation following the trigeminal V1 branch and, later, their entrance into the eye along the ciliary nerves and their finest iris branches. Our concept provides an explanation not only for the specific distribution of ocular melanocytic lesions, including uveal and iris nevi, but also for the different locations depending on the metastatic potential of the ocular melanoma. Though speculative, the higher metastatic potential of posterior uveal melanomas compared to iris melanomas may be related to a less differentiated stage in the maturation of migrating melanocytes in the posterior segment compared to the anterior segment of the eye. However, there is a need of further studies focusing on cell differentiation markers of melanocytes at different locations in the eye.

Efficient Characterization of Parametric Uncertainty of Complex (Bio)chemical Networks.

Parametric uncertainty is a particularly challenging and relevant aspect of systems analysis in domains such as systems biology where, both for inference and for assessing prediction uncertainties, it is essential to characterize the system behavior globally in the parameter space. However, current methods based on local approximations or on Monte-Carlo sampling cope only insufficiently with high-dimensional parameter spaces associated with complex network models. Here, we propose an alternative deterministic methodology that relies on sparse polynomial approximations. We propose a deterministic computational interpolation scheme which identifies most significant expansion coefficients adaptively. We present its performance in kinetic model equations from computational systems biology with several hundred parameters and state variables, leading to numerical approximations of the parametric solution on the entire parameter space. The scheme is based on adaptive Smolyak interpolation of the parametric solution at judiciously and adaptively chosen points in parameter space. As Monte-Carlo sampling, it is "non-intrusive" and well-suited for massively parallel implementation, but affords higher convergence rates. This opens up new avenues for large-scale dynamic network analysis by enabling scaling for many applications, including parameter estimation, uncertainty quantification, and systems design.

The use of dermatoscopy in diagnosis and therapy of nonmelanocytic skin cancer.

Today, dermatoscopy is an integral part of every clinical skin examination, as it markedly enhances the early detection of melanocytic and nonmelanocytic skin cancer (NMSC) compared to naked-eye inspection. Besides its diagnostic use, this noninvasive method is increasingly important in the selection of as well as the response assessment to various therapies used for NMSC, including basal cell carcinoma, actinic keratoses, squamous cell carcinoma, and also rare tumors such as Merkel cell carcinoma, angiosarcoma, or dermatofibrosarcoma protuberans. Thus, dermatoscopy is a valid tool for the preoperative assessment of tumor margins in basal cell carcinoma, but also for follow-up of actinic keratoses after topical treatment. The present article presents an overview on the use of dermatoscopy in the diagnosis and therapy of various types of NMSC.

Analysis of functional polymorphisms in apoptosis-related genes in primary open angle glaucoma.

PURPOSE: Glaucoma is a disease with high heritability in which the degradation of retinal ganglion cells occurs via apoptosis. Therefore, we investigated the role of four functional apoptosis-related gene variants (Akt1 rs1130233, Bax rs4645878, Fas rs223476, and FasL rs763110) in patients with primary open angle glaucoma. METHODS: 334 patients with primary open angle glaucoma and 334 controls were recruited for this case-control study. The main outcome measures were genotype distribution and allelic frequencies determined with PCR. RESULTS: After adjustment for multiple testing, no significant difference in either the genotype distribution or the allelic frequencies of any investigated gene variant was found. CONCLUSIONS: Our findings indicate that the investigated gene polymorphisms are unlikely to be major risk factors for primary open angle glaucoma in Caucasian patients.

PSA bounce after ¹²5I-brachytherapy for prostate cancer as a favorable prognosticator.

BACKGROUND: Permanent low-dose-rate brachytherapy (BT) with iodine 125 is an established curative treatment for localized prostate cancer. After treatment, prostate-specific antigen (PSA) kinetics may show a transient rise (PSA bounce). Our aim was to investigate the association of PSA bounce with biochemical control. PATIENTS AND METHODS: Patients treated with BT in Switzerland were registered in a prospective database. Only patients with a follow-up of at least 2 years were included in our analysis. Clinical follow-up and PSA measurements were assessed after 1.5, 3, 6, and 12 months, and annually thereafter. If PSA increased, additional follow-up visits were scheduled. Cases of PSA bounce were defined as a rise of at least 0.2 ng/ml above the initial PSA nadir with a subsequent decline to or below the initial nadir without treatment. Biochemical failure was defined as a rise to nadir + 2 ng/ml. RESULTS: Between March 2001 and November 2010, 713 patients with prostate cancer undergoing BT with at least 2 years of follow-up were registered. Median follow-up time was 41 months. Biochemical failure occurred in 28 patients (3.9 %). PSA bounce occurred in 173 (24.3 %) patients; only three (1.7 %) patients with PSA bounce developed biochemical failure, in contrast to 25 (4.6 %) patients without previous bounce (p < 0.05). The median time to bounce was 12 months, the median time to biochemical failure was 30 months. The median bounce increase was 0.78 ng/ml. Twenty-eight patients with bounce (16.5 %) had a transient PSA rise of + 2 ng/ml above the nadir. CONCLUSION: In most cases, an early increase in PSA after BT indicates PSA bounce and is associated with a lower risk of biochemical failure.

Direct solution of the Chemical Master Equation using quantized tensor trains.

The Chemical Master Equation (CME) is a cornerstone of stochastic analysis and simulation of models of biochemical reaction networks. Yet direct solutions of the CME have remained elusive. Although several approaches overcome the infinite dimensional nature of the CME through projections or other means, a common feature of proposed approaches is their susceptibility to the curse of dimensionality, i.e. the exponential growth in memory and computational requirements in the number of problem dimensions. We present a novel approach that has the potential to "lift" this curse of dimensionality. The approach is based on the use of the recently proposed Quantized Tensor Train (QTT) formatted numerical linear algebra for the low parametric, numerical representation of tensors. The QTT decomposition admits both, algorithms for basic tensor arithmetics with complexity scaling linearly in the dimension (number of species) and sub-linearly in the mode size (maximum copy number), and a numerical tensor rounding procedure which is stable and quasi-optimal. We show how the CME can be represented in QTT format, then use the exponentially-converging hp-discontinuous Galerkin discretization in time to reduce the CME evolution problem to a set of QTT-structured linear equations to be solved at each time step using an algorithm based on Density Matrix Renormalization Group (DMRG) methods from quantum chemistry. Our method automatically adapts the "basis" of the solution at every time step guaranteeing that it is large enough to capture the dynamics of interest but no larger than necessary, as this would increase the computational complexity. Our approach is demonstrated by applying it to three different examples from systems biology: independent birth-death process, an example of enzymatic futile cycle, and a stochastic switch model. The numerical results on these examples demonstrate that the proposed QTT method achieves dramatic speedups and several orders of magnitude storage savings over direct approaches.

Is absorption of irrigation fluid a problem in Thulium laser vaporization of the prostate? A prospective investigation using the expired breath ethanol test.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a prevalent entity in elderly men. If medical treatment fails, monopolar transurethral resection of the prostate (TUR-P) is still considered as the standard treatment. The proportion of high-risk patients with cardiac comorbidities increases and TUR-P goes along with a relevant perioperative risk. Especially large volume influx of irrigation fluid and transurethral resection syndrome (TUR syndrome) represent serious threats to these patients. Using isotonic saline as irrigation fluid like in transurethral laser vaporization (TUV-P), TUR syndrome can be prevented. However, no prospective trial has ever assessed occurrence or extent of irrigation fluid absorption in Thulium Laser TUV-P. METHODS/DESIGN: This is a single-center prospective trial, investigating, if absorption of irrigation fluid occurs during Thulium Laser TUV-P by expired breath ethanol test. The expired breath ethanol technique is an established method of investigating intraoperative absorption of irrigation fluid: A tracer amount of ethanol is added to the irrigation fluid and the absorption of irrigation fluid can be calculated by measuring the expiratory ethanol concentrations of the patient with an alcohol breathalyzer. Fifty consecutive patients undergoing TUV-P at our tertiary referral center are included into the trial. Absorption volume of irrigation fluid during Thulium Laser TUV-P is defined as primary endpoint. Pre- to postoperative changes in bladder diaries, biochemical and hematological laboratory findings, duration of operation and standardized questionnaires are assessed as secondary outcome measures. DISCUSSION: The aim of this study is to assess the safety of Thulium Laser TUV-P in regard to absorption of irrigation fluid.

Bipolar versus monopolar transurethral resection of the prostate: results of a comparative, prospective bicenter study--perioperative outcome and long-term efficacy.

OBJECTIVES: To compare bipolar and monopolar transurethral resection of the prostate (TURP) in a comparative prospective study at two urology centers. METHODS: Of 212 patients with symptomatic benign prostatic hyperplasia entered prospectively into the study, 111 underwent bipolar and 101 monopolar TURP. Patients were treated in two consecutive series with each surgical method at both centers. Improvement in peak flow rate, postvoid residual, International Prostate Symptom Score, and quality of life score postoperatively and at 3, 12, 24 and 36 months, as well as long-term adverse events were compared. Regarding safety, duration of surgery, postoperative catheterization and hospitalization time, amount of fluid absorption, frequency of transurethral resection (TUR) syndrome, and risk of hemorrhage were evaluated. RESULTS: Patient characteristics of the two series were comparable. The risk of developing TUR syndrome (p = 0.32) and bleeding tendency (p = 0.52) did not differ significantly between groups. Significant differences were seen for duration of surgery and resection speed. All functional parameters improved significantly during follow-up, with no relevant differences between surgical groups. CONCLUSIONS: Since no major differences in efficacy and safety were seen between the surgical groups, we feel that the monopolar technique still has a valuable place in TURP.

De Rham compatible Deep Neural Network FEM.

On general regular simplicial partitions T of bounded polytopal domains Ω⊂Rd, d∈{2,3}, we construct exact neural network (NN) emulations of all lowest order finite element spaces in the discrete de Rham complex. These include the spaces of piecewise constant functions, continuous piecewise linear (CPwL) functions, the classical "Raviart-Thomas element", and the "Nédélec edge element". For all but the CPwL case, our network architectures employ both ReLU (rectified linear unit) and BiSU (binary step unit) activations to capture discontinuities. In the important case of CPwL functions, we prove that it suffices to work with pure ReLU nets. Our construction and DNN architecture generalizes previous results in that no geometric restrictions on the regular simplicial partitions T of Ω are required for DNN emulation. In addition, for CPwL functions our DNN construction is valid in any dimension d≥2. Our "FE-Nets" are required in the variationally correct, structure-preserving approximation of boundary value problems of electromagnetism in nonconvex polyhedra Ω⊂R3. They are thus an essential ingredient in the application of e.g., the methodology of "physics-informed NNs" or "deep Ritz methods" to electromagnetic field simulation via deep learning techniques. We indicate generalizations of our constructions to higher-order compatible spaces and other, non-compatible classes of discretizations, in particular the "Crouzeix-Raviart" elements and Hybridized, Higher Order (HHO) methods.

Single-centre evaluation of the extraperitoneal and transperitoneal approach in robotic-assisted radical prostatectomy.

OBJECTIVE: Robotic-assisted radical prostatectomy (RARP) is feasible using either an extraperitoneal (EP) or a transperitoneal (TP) approach. This study reports on the experience of a single hospital using both techniques. MATERIAL AND METHODS: From July 2009 to March 2011, 170 patients underwent RARP. EP was chosen in 103 patients and TP in 67. TP was preferred in cases previous mesh hernia repair or if extended lymph-node dissection (LND) was considered necessary. Otherwise, EP was performed; it was preferred in cases of obesity (body mass index (BMI) > 30 kg/m(2)) or previous intra-abdominal surgery. RESULTS: There were no significant differences in preoperative mean age (64.4 vs 65.6 years), BMI (26.5 vs 26.3 kg/m(2)) or prostate size (51.8 vs 55.8 cm(3)) between EP and TP patients. Owing to preoperative selection criteria, prostate-specific antigen levels and the average Gleason score were significantly lower in EP than in TP patients (p < 0.001). Whereas access time and time for anastomosis did not differ significantly (21 vs 19 min, p = 0.11, and 26 vs 24 min, p = 0.36, respectively), overall surgical time was significantly longer in TP (225 vs 191 min, p < 0.001). Blood loss was equal in both groups (EP 276 vs TP 281 ml, p = 0.88). Complication rates were lower in EP (n = 7, 6.8% vs n = 8, 12%, p = 0.024). Time until first defecation and last analgesic treatment were significantly shorter in EP (p < 0.05). CONCLUSIONS: The results of the current evaluation underline the clinical advantages of an extraperitoneal approach for RARP. However, a transperitoneal approach is still considered necessary for extended LND or special clinical conditions. Robotic teams should be trained using both approaches.

Crystal structure and Hirshfeld surface analysis of N-{[diphen-yl(vin-yl)sil-yl]meth-yl}-2-methyl-propan-2-ammonium chloride.

N-{[Diphen-yl(vin-yl)sil-yl]meth-yl}-2-methyl-propan-2-amine, C19H25NSi, is a newly synthesized secondary amino-methyl-silane that can be used, for example, to study carboli-thia-tion reactions of vinyl-silanes. Because the neutral compound did not crystallize well, the hydro-chloride salt, C19H26NSi+·Cl-, was formed, in which the two chloride ions in the asymmetric unit have crystallographic site symmetry. An unusually long Si-C bond of 1.9117 (10) Šis observed in the cation, which may be ascribed to electronic effects due to the ß N+ species. In the crystal, the cations and anions are linked by N-H⋯Cl hydrogen bonds to generate [001] chains. To further investigate the inter-molecular inter-actions, a Hirshfeld surface analysis was performed, which showed that H⋯H, C⋯H/H⋯C and H⋯Cl/Cl⋯H contacts contribute 70.4, 20.0 and 8.3%, respectively.

Gender differences in albumin and ascorbic acid in the vitreous antioxidant system.

Ascorbic acid is present at high concentrations in the vitreous and plays a central role in vitreous redox chemistry. Albumin is the main protein in the vitreous with antioxidant properties and occurs in different oxidation states, which can be used as redox indicators, but have not been studied in the vitreous. This study, therefore, addressed the vitreous redox state of cysteine-34 of albumin in relation to the ascorbic acid content, which has been suggested to exert a main function in detoxifying reactive oxygen in the vitreous. A total of 58 vitreous samples obtained from patients undergoing vitrectomy were analyzed for (i) human mercaptalbumin (HMA), the reduced thiol form; (ii) human non-mercaptalbumin1 (HNA1), a reversible oxidative modification with a disulfide at cysteine-34; and (iii) human non-mercaptalbumin2 (HNA2), a non-reversibly (highly) oxidized form of albumin; as well as (iv) ascorbic acid concentrations, to study possible relations. In addition, blood samples were taken to compare albumin redox state between plasma and the vitreous. Vitreous albumin showed greater variability in the redox state of cysteine-34 and a shift to the oxidized fractions compared to plasma albumin (P < 0.001). A strong positive relation was observed between the vitreous ascorbic acid concentrations and the reversibly oxidized form, HNA1 (P < 0.001), and a negative relation with the reduced form, HMA. Positive relations between ascorbic acid and HNA1 in the vitreous were stronger in men than in women. In contrast to HMA and HNA1, there was a distinct gender difference noted for the irreversibly oxidized form, HNA2. While males showed a positive relation between the vitreous ascorbic acid concentrations and HNA2, there was no correlation found with HNA2 in females. Our results support the view that ascorbic acid, by decreasing either directly or indirectly the concentrations of molecular oxygen, generates hydrogen peroxide, and that thiols, including HMA, are acting as antioxidants. This study for the first time provides evidence that vitreous albumin can be used as a marker molecule for the appearance of reactive oxygen species in the vitreous of patients undergoing vitrectomy. Moreover, it can be shown that there are gender differences in vitreous ascorbic acid and albumin concentrations as well as in oxidation state of vitreous albumin.

A Retrospective Study of 199 Xen45 Stent Implantations From 2014 to 2016.

PURPOSE: The aim of this study is to determine the postoperative course after Xen45 Gel Stent implantation at the Medical University of Graz from 2014-2016. METHODS: Single-center, retrospective study. All patients with Xen implantation between 2014 and 2016 were included. Clinical records and reports received from supervising ophthalmologists were used for evaluations. Investigated parameters were intraocular pressure (IOP), the number of medications, visual acuity, and the number of previous operations, IOP-follow-up, intraoperative and postoperative complications, the rate of interventions (needling), and additionally performed surgeries. RESULTS: Xen was implanted in 199 eyes of 160 patients. Mean preoperative IOP was 22.8±6.9 mm Hg on 2.9±1.0 IOP-lowering medication. After 12 months follow-up, mean IOP was 17.1±5.9 mm Hg (n=89, P<0.0001; mean reduction of 22.7%) on 1.8±1.4 (n=87; P<0.0001) IOP-lowering medications. There were no intraoperative complications and in two cases (1.0%) severe postoperative adverse events occurred (aqueous misdirection and late-onset endophthalmitis). Postoperative needling was indicated in 44 cases (22.1%), while in 28 cases (14.1%) an additional glaucoma surgery was performed. CONCLUSIONS: Our results indicate that Xen implantation is an effective surgical intervention leading to a significant reduction of IOP and number of medications with a low rate of complications. An attentive postoperative management seems to be mandatory.

Shared Decision-Making for Patients with Advanced Urological Malignancies: Evaluation of a Joint Urological-Oncological Clinic Model.

BACKGROUND: To provide rapid evaluation of patients with advanced urological malignancies, a joint urological-oncological clinic was initiated at our institution in January 2015. We present the first 3-year evaluation of this joint urological-oncological clinic in Switzerland. METHOD: We performed a retrospective analysis of the characteristics and treatment of all patients reviewed at the joint clinic between January 2015 and December 2017. Statistical analysis was performed by survival analysis. A patient satisfaction questionnaire was handed out to new patients (from April to September 2017). RESULTS: A total of 135 new patients were counseled in the joint clinic and 563 consultations were performed in the period from January 2015 to December 2017. The majority were men with prostate cancer (85%), followed by bladder cancer (9%), and renal cell carcinoma (4%). Men with newly diagnosed metastatic prostate cancer (n = 69) received ADT alone (57%), ADT with docetaxel or abiraterone (33%), and metastasis-directed therapy (10%). High rates of patient satisfaction were reported based on the questionnaire. CONCLUSIONS: The joint clinic model has been successfully implemented at our institution and continues on a weekly basis. The clinic is increasingly used, not only for newly diagnosed metastatic prostate cancer, but also for other complex uro-oncological cases. The clinic allows optimized oncological treatment without delay and with a reduced effort for patients.