Validation of the adaptive scan method in the quest for time-efficient methods of testing auditory processes.

A major barrier to the clinical application of psychophysical testing of central auditory processes is the time required to obtain precise estimates of different listening abilities. In this study, we validate a novel adaptive scan (AS) method of threshold estimation that is designed to adapt on a range of values around threshold rather than on a single threshold value. This method has the advantage of providing the listener with greater familiarity with the stimulus characteristics near threshold while maintaining precise measurement and increasing time-efficiency. Additionally, we explore the time-efficiency of AS through comparison with two more conventional adaptive algorithms and the method of constant stimuli in two common psychophysical tasks: the detection of a gap in noise and the detection of a tone in noise. Seventy undergraduates without hearing complaints were tested using all four methods. The AS method provided similar threshold estimates with similar precision to those from the other adaptive methods and, thus, it is a valid adaptive method of psychophysical testing. We also provide an analysis of the AS method based on precision metrics to propose a shortened version of the algorithm that maximizes the time/precision tradeoff and can achieve similar thresholds to the adaptive methods tested in the validation. This work lays the foundation for using AS across a wide variety of psychophysical assessments and experimental situations where different levels of precision and/or time-efficiency may be required.

MR Imaging and Clinical Characteristics of Diffuse Glioneuronal Tumor with Oligodendroglioma-like Features and Nuclear Clusters.

BACKGROUND AND PURPOSE: Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC) is a new, molecularly defined glioneuronal CNS tumor type. The objective of the present study was to describe MR imaging and clinical characteristics of patients with DGONC. MATERIALS AND METHODS: Preoperative MR images of 9 patients with DGONC (median age at diagnosis, 9.9 years; range, 4.2-21.8 years) were reviewed. RESULTS: All tumors were located superficially in the frontal/temporal lobes and sharply delineated, displaying little mass effect. Near the circle of Willis, the tumors encompassed the arteries. All except one demonstrated characteristics of low-to-intermediate aggressiveness with high-to-intermediate T2WI and ADC signals and bone remodeling. Most tumors (n = 7) showed a homogeneous ground-glass aspect on T2-weighted and FLAIR images. On the basis of the original histopathologic diagnosis, 6 patients received postsurgical chemo-/radiotherapy, 2 were irradiated after surgery, and 1 patient underwent tumor resection only. At a median follow-up of 61 months (range, 10-154 months), 6 patients were alive in a first complete remission and 2 with stable disease 10 and 21 months after diagnosis. The only patient with progressive disease was lost to follow-up. Five-year overall and event-free survival was 100% and 86±13%, respectively. CONCLUSIONS: This case series presents radiomorphologic characteristics highly predictive of DGONC that contrast with the typical aspects of the original histopathologic diagnoses. This presentation underlines the definition of DGONC as a separate entity, from a clinical perspective. Complete resection may be favorable for long-term disease control in patients with DGONC. The efficacy of nonsurgical treatment modalities should be evaluated in larger series.

MiR-205-driven downregulation of cholesterol biosynthesis through SQLE-inhibition identifies therapeutic vulnerability in aggressive prostate cancer.

Prostate cancer (PCa) shows strong dependence on the androgen receptor (AR) pathway. Here, we show that squalene epoxidase (SQLE), an enzyme of the cholesterol biosynthesis pathway, is overexpressed in advanced PCa and its expression correlates with poor survival. SQLE expression is controlled by micro-RNA 205 (miR-205), which is significantly downregulated in advanced PCa. Restoration of miR-205 expression or competitive inhibition of SQLE led to inhibition of de novo cholesterol biosynthesis. Furthermore, SQLE was essential for proliferation of AR-positive PCa cell lines, including abiraterone or enzalutamide resistant derivatives, and blocked transactivation of the AR pathway. Inhibition of SQLE with the FDA approved antifungal drug terbinafine also efficiently blocked orthotopic tumour growth in mice. Finally, terbinafine reduced levels of prostate specific antigen (PSA) in three out of four late-stage PCa patients. These results highlight SQLE as a therapeutic target for the treatment of advanced PCa.

Evaluation of a curved surgical prototype in a human larynx.

PURPOSE: It is not always possible to create linear access to the larynx using a rigid operating laryngoscope for microlaryngoscopy. In this study, we evaluate the usability of a novel curved surgical prototype with flexible instruments for the larynx (sMAC) in a simulation dummy and human body donor. METHODS: In a user study (n = 6), head and neck surgeons as well as medical students tested the system for visualization quality and accessibility of laryngeal landmarks on an intubation dummy and human cadaver. A biopsy of the epiglottis was taken from the body donor. Photographic and time documentation was carried out. RESULTS: The sMAC system demonstrated general feasibility for laryngeal surgery. Unlike conventional microlaryngoscopy, all landmarks could be visualized and manipulated in both setups. Biopsy removal was possible. Visibility of the surgical field remained largely unobstructed even with an endotracheal tube in place. Overall handling of the sMAC prototype was satisfactorily feasible at all times. CONCLUSION: The sMAC system could offer an alternative for patients, where microlaryngoscopy is not applicable. A clinical trial has to clarify if the system benefits in clinical routine.

The tibial cut in total knee arthroplasty influences the varus alignment, the femoral roll-back and the tibiofemoral rotation in patients with constitutional varus.

PURPOSE: Different alignment types for a better outcome after TKA were described. However, it is not clear how kinematic alignment influences knee joint kinematic. The purpose of this study was to analyze whether adapted tibial cuts in constitutional varus knees affect knee joint kinematics regarding femoral roll-back, varus/valgus angle, and femorotibial rotation. METHODS: Seven cadaveric knees with constitutional varus alignment were examined in the native state and after implantation of a cruciate retaining (CR)-TKA with 0°, 3° and 6° tibia cuts using an established knee joint simulator. The effects of varus alignment on femorotibial rollback and rotation was determined. In addition, the native knee joint and different tibial cuts in CR-TKA were compared with Student's t test. RESULTS: Total knee replacement with a 3° and 6° varus tibia cut had the greatest varus deviation to the native knee (mean 1.6° ± 0.09°, respectively); while, knees with a 0° (mean 0.2° ± 0.01°) tibia cut were most similar to the constitutional varus knee joint. The femoral roll-back in the medial compartment was increased in the native knee (5.7-12.5 mm). A 6° varus cut had a restricted translation in the medial compartment (2-3.2 mm). In the lateral compartment, the extensive translation was observed with a 0° varus cut, followed by 3° and 6° and the native knee. All cuts showed significantly different mean values. Only the cuts at 3° and at 6° in the medial compartment and the cuts at 0° and at 3° in the lateral compartment did not differ significantly. In respect to tibiofemoral rotation, 0° and 3° varus cuts across all loads had the least difference to the native knee (3.4°), with a 0° varus cut showing a higher absolute internal rotation of the tibia than the native knee. Changes in knee kinematics of the tibiofemoral rotation showed significantly different mean values. CONCLUSION: The potentially improved outcome parameters in TKA with adapted tibia cuts in constitutional varus knees cannot be completely explained by the changes to knee kinematics. Mechanical alignment seems to result in more balanced load distribution and kinematics more closely resembling the native knee. From a kinematic point of view, it is not recommended to place the tibia in more than 3° of varus. LEVEL OF EVIDENCE: Biomechanical study.

Degeneration alters the biomechanical properties and structural composition of lateral human menisci.

OBJECTIVE: Because the literature relating to the influence of degeneration on the viscoelasticity and tissue composition of human lateral menisci remains contradictory or completely lacking, the aim of this study was to fill these gaps by comprehensively characterising the biomechanical properties of menisci with regard to the degree of degeneration. DESIGN: Meniscal tissue from 24 patients undergoing a total knee replacement was collected and the degeneration of each region classified according to Pauli et al. For biomechanical characterisation, compression and tensile tests were performed. Additionally, the water content was determined and infrared (IR) spectroscopy was applied to detect changes in the structural composition, particularly of the proteoglycan and collagen content. RESULTS: With an increasing degree of degeneration, a significant decrease of the equilibrium modulus was detected, while simultaneously the water content and the hydraulic permeability significantly increased. However, the tensile modulus displayed a tendency to decrease with increasing degeneration, which might be due to the significantly decreasing amount of collagen content identified by the IR measurements. CONCLUSION: The findings of the current study may contribute to the understanding of meniscus degeneration, showing that degenerative processes appear to mainly worsen viscoelastic properties of the inner circumference by disrupting the collagen integrity.

Osseointegration of titanium implants with a novel silver coating under dynamic loading.

Postoperative implant-associated infections are a severe complication in orthopaedics and trauma surgery. To address this problem, a novel implant coating was recently developed, which allows for the release of low concentrations of bactericidal silver. For an intended use on load-bearing endoprostheses, stable bone integration is required. The aim of the present study was to evaluate the biocompatibility and osseointegration of titanium implants with the novel coating in a mechanically loaded bone-defect model in sheep. Silver-coated devices were implanted into weight-bearing and non-weight-bearing tibial and femoral bone defects whereas, in the control group, uncoated titanium implants were inserted. The bony integration of the implants was assessed mechanically and histologically after 6 months. Silver concentrations were assessed in peripheral blood, liver, kidney and local draining lymph nodes as well as at the implantation site. After 6 months, shear strength at the interface and bone apposition to the implant surface were not significantly different between coated and uncoated devices. Mechanical loading reduced bony integration independently of the coating. Silver content at the implantation site was larger in the group with silver-coated implants, yet it remained below toxic levels and no cytotoxic side effects were observed. Concluding, the novel antibacterial silver coating did not negatively influence bone regeneration or implant integration under mechanically unloaded and even loaded conditions, suggesting that the silver coating might be suitable for orthopaedic load-bearing implants, including endoprostheses.

Modified Candy-Package technique vs Cerclage technique for refixation of the lesser trochanteric fragment in pertrochanteric femoral fractures. A biomechanical comparison of 10 specimens.

OBJECTIVES: Separation of the lesser trochanteric fragment in pertrochanteric 3-part fractures leads to a significant weakening of the medial cortical wall. Because of the attachment of the Iliopsoas muscle to this structure, the lesser trochanteric fragment tends to cranial dislocation along this muscle's action direction. Refixation of these fractures using an intramedullary nail and an additional wiring osteosynthesis can be considered an operative standard. Based on an intramedullary osteosynthesis procedure, the question was raised whether a 2-point fixation method was favourable over a 1-point method regarding the pull-out resistance of the lesser trochanteric fragment against the Iliopsoas muscle's force. METHODS: Based on an intramedullary osteosynthesis (PFNA, DePuy/Synthes/SUI), two groups á five human femora were defined depending on the refixation technique of the lesser trochanteric fragment (1-point supertrochanteric "Cable" vs 2-point super/subtrochanteric fixation "Candy-Package" performed with a 1.25-mm steel cerclage). The specimens were tested using a novel traction setup, simulating the activity pattern of the Iliopsoas muscle. The target value was the resistance of the refixated lesser trochanteric fragment against a defined pull-out force produced by the Iliopsoas muscle. The main parameters considered were the peak traction force (Fmax) and the maximum summative work (WFmax) at construct failure. RESULTS: The Fmax and WFmax displayed a significant difference in favour of the Candy-Package (2-point super/subtrochanteric fixation) group (822 N vs. 476 N, 13.8 k Nmm vs 4.4 k Nmm, respectively; P = 0.01). CONCLUSIONS: The Candy-Package technique is a method that displays significantly more resistance than a single cerclage osteosynthesis regarding fragment loosening under the application of a simulated Iliopsoas muscle force in the course of a biomechanical proximal femoral 3-part fracture model.

[Immuno-oncological approaches in the perioperative therapy of muscle invasive bladder cancer]. / Immunonkologische Ansätze in der perioperativen Therapie des muskelinvasiven Urothelkarzinoms.

Perioperative chemotherapy has become a standard treatment for muscle invasive bladder cancer and is recommended by national and international guidelines. The treatment of metastatic urothelial cancer evolved by the use of immune-modulating therapies like checkpoint inhibitors. Many clinical trials have been initiated which try to evaluate the role of immune checkpoint inhibition in the neoadjuvant and adjuvant setting. These trials focus not only on monotherapy, but also on the combination of checkpoint inhibitors with classical chemotherapy or with local radiation therapy (radioimmunotherapy). In neoadjuvant radioimmunotherapy, the radiation is supposed to act as a sensitizer for the systemic effects of checkpoint inhibition, in addition to the local effects. This review presents and discusses current trials and published results for perioperative immunomodulating treatment-alone or in combination-in muscle invasive bladder cancer.

The tibial cut influences the patellofemoral knee kinematics and pressure distribution in total knee arthroplasty with constitutional varus alignment.

PURPOSE: The current literature suggests that kinematic total knee arthroplasty (kTKA) may be associated with better outcome scores in patients with constitutional varus alignment. The underlying patellofemoral kinematic changes (patella tilting and patella tracking) and patellofemoral pressure distribution have not yet been described. The present study compared the effects of different tibial cuts, as used in kTKA, on patellofemoral knee kinematics and the pressure distribution, in addition to comparisons with the natural constitutional varus knee. METHODS: Seven cadaveric knee joints with constitutional varus alignment were examined in the native state and after 0°, 3°, or 6° tibial cut cruciate-retaining (CR)-TKA using an established knee joint simulator. The effects on patella rotation/patella tilting, patellofemoral pressure, and patellofemoral length ratios (= patella tracking) were determined. In addition, the natural knee joint and different tibial cuts in CR-TKA were compared (Student's t test). RESULTS: In the patellofemoral joint, 6° CR-TKA was associated with the greatest similarity with the natural constitutional varus knee. By contrast, knees subjected to 0° CR-TKA exhibited the largest deviations of patellar kinematics. The smallest difference compared with the natural knee joint concerning patella tilting was found for 6° CR-TKA (mean 0.4°, p < 0.001), and the largest difference was noted for 0° CR-TKA (mean 1.7°, p < 0.001). Concerning patellofemoral pressure, 6° CR-TKA resulted in outcomes most similar to the natural knee joint, featuring a mean difference of 3 MPa. The largest difference from the natural knee joint was identified for 0° CR-TKA, with an average difference of 8.1 MPa (p < 0.001; total mean 17.7 MPa). Meanwhile, 3° and 6° CR-TKA induced medialization of the patella, with the latter inducing the largest medialization value of 4.5 mm at 90° flexion. CONCLUSIONS: The improved outcome parameters in kTKA described in the literature could be attributable to the similar kinematics of the patellofemoral joint relative to the normal state. The current study confirmed the similar kinematics between the native constitutional varus knee joint and knee joints subjected to 3° or 6° CR-TKA (patellofemoral rotation/patella tilting and patella pressure). Conversely, there was pronounced medialization of the patella following 6° CR-TKA. Patella pressure and patella tilting are described in the literature as possible causes of anterior knee pain after TKA, whereas medialization of the patella, which is also influenced by other causes, might play a subordinate role. LEVEL OF EVIDENCE: V, Biomechanical study.

Oculodentodigital Dysplasia: A Hypomyelinating Leukodystrophy with a Characteristic MRI Pattern of Brain Stem Involvement.

Oculodentodigital dysplasia, a rare genetic disorder caused by mutations in the gene encoding gap junction protein 1, classically presents with typical facial features, dental and ocular anomalies, and syndactyly. Oligosymptomatic patients are common and difficult to recognize, in particular if syndactyly is absent. Neurologic manifestation occurs in approximately 30% of patients, and leukodystrophy or T2 hypointensity of gray matter structures or both have been noted in individual patients. To investigate MR imaging changes in oculodentodigital dysplasia, we retrospectively and systematically reviewed 12 MRIs from 6 genetically confirmed patients. Diffuse supratentorial hypomyelination, T2-hypointense Rolandic and primary visual cortex, and symmetric involvement of middle cerebellar peduncle, pyramidal tract, and medial lemniscus was present in all, T2-hypointense pallidum and dentate nucleus in 2 patients each. This consistent, characteristic pattern of diffuse supratentorial hypomyelination and brain stem involvement differs from other hypomyelinating and nonhypomyelinating leukodystrophies with brain stem involvement, and its recognition should trigger genetic testing for oculodentodigital dysplasia.

[Molecular tumor board prostate cancer]. / Molekulares Tumorboard Prostatakarzinom.

In modern oncology, molecular tumor boards are the interface between the public healthcare system and clinical research institutions. An interdisciplinary team of medical and scientific experts assesses if extensive molecular testing for tumor profiling is appropriate and discusses therapeutic options for patients with newly diagnosed treatable alterations. In the field of metastatic prostate cancer, patients especially with a strong family history, young age of diagnosis and those who have exhausted standard treatments may benefit from molecular profiling. Expression of the androgen receptor splice variant 7 (AR-V7) predicts nonresponse to next-generation AR-directed therapy like abiraterone or enzalutamide. Different blood tests for AR-V7 detection are now commercially available. Mutations in the DNA repair pathway are another frequent event in metastatic prostate cancer. Homologous recombination defects sensitize cancer cells to poly(ADP-ribose) polymerase (PARP) inhibitors. In the TOPARP-A trial, the PARP inhibitor olaparib led to high response rates (88%) in patients with mutated DNA repair genes. Furthermore, patients with DNA mismatch repair deficiency and/or microsatellite instability seem to benefit from PD-1 inhibitors, particularly pembrolizumab. At this time neither PARP inhibitors nor PD-1 inhibitors are approved for metastatic prostate cancer treatment in Germany. Therefore, a recommendation of a molecular tumor board for biomarker-matched off-label use of approved drugs across entity barriers will support coverage by health insurance.

Complete concentric collapse at the soft palate in sleep endoscopy: what change is possible after UPPP in patients with CPAP failure?

PURPOSE: The aim of this work was to assess whether uvulopalatopharyngoplasty in patients with failure for positive airway pressure not only reduces the degree of obstructive sleep apnea but also to determine as well if it changes the collapse pattern of the soft palate and thereby fulfills the qualifications for implementing upper airway stimulation (UAS) as an adjunctive solution. METHOD: Fifteen patients with intolerance for positive airway pressure were included in this retrospective cohort study. Polygraphy and drug-induced sleep endoscopy were used in order to evaluate the reduction of the apnea-hypopnea index (AHI), as well as the change of collapse pattern at the soft palate level before and about 3 months after uvulopalatopharyngoplasty and tonsillectomy (TE-UPPP). RESULTS: In 93% of the patients, a postoperative change of the initially complete concentric palatal collapse pattern could be found during drug-induced sleep endoscopy. In one patient, no obstruction at all was seen at the soft palatal level. Only one patient still presented with a complete concentric collapse at velum level. AHI decreased from mean 34.7 events per hour to 20.2/h and oxygen desaturation index from 25.3 events per hour to 16.1/h. CONCLUSION: Patients seeking for positive airway pressure alternatives could not only benefit from reduction of AHI by TE-UPPP postoperatively; additionally, by changing the collapse pattern at the soft palate, they might also fulfill criteria for upper airway stimulation (UAS) in case of persistent OSA of at least moderate degree.

Correlative SIM-STORM Microscopy.

The ability to specifically label subcellular structures or even proteins of interest in combination with the ability to look at live specimens turned fluorescence light microscopy into an invaluable tool. However, conventional light microscopy is diffraction limited, which restricts the lateral resolution to around 200 nm laterally and 600-800 nm axially. In 2014, the Nobel Prize in Chemistry was awarded to Eric Betzig, Stefan W. Hell, and William E. Moerner for the development of super-resolved fluorescent microscopy techniques. Since then, it has become evident that imaging techniques that enable the visualization of structures below the diffraction limit are essential for the field of life sciences. However, each one of these approaches has inherent advantages and limitations. Here, we describe an imaging workflow suitable for combining structured illumination microscopy (SIM) with direct stochastic optical reconstruction microscopy (dSTORM) data. This is invaluable, since it allows us to put highly resolved dSTORM data into its cellular context.

Influence of tibial hybrid fixation on graft tension and stability in ACL double-bundle reconstruction.

PURPOSE: Initial graft tension in anterior cruciate ligament (ACL) reconstruction affects stability and tension loss at follow-up. This study investigated the influence of hybrid tibial fixation in 3-tunnel double-bundle ACL reconstruction on initial graft tension and tension change and stability under anterior and combined rotatory loads. METHODS: Eleven fresh-frozen cadaveric knees were reconstructed with an ACL double bundle using a 3-tunnel technique. Grafts were tightened to 80 N in 60° (AM bundle) and 15° (PL bundle) of flexion. Anterior tibial translation under 134 N of anterior shear load and translation under combined rotatory and valgus loads (10 Nm valgus stress, 4 Nm internal tibial torque) were determined at 0°, 30°, 60°, and 90° flexion. In addition, graft tension under continuous passive motion was determined. Intact, ACL-resected and ACL-reconstructed joints with either tibial extracortical graft fixation or extracortical plus supplemental aperture graft fixation (hybrid fixation) were tested. RESULTS: Hybrid fixation did not increase graft tension in either bundle during fixation or in motion without additional load. AM-bundle tension increased (p < 0.05) at 0° under combined rotatory and valgus loads and at 30° and 60° under both loading conditions without decreasing the anterior tibial translation. PL-bundle tension increased (p < 0.05) only at 90° under combined rotatory and valgus loads. CONCLUSIONS: Tibial hybrid fixation in 3-tunnel double-bundle ACL reconstruction increases time-zero AM- and PL-bundle tensions under loading conditions, generating greater construct stiffness. This could lead to a longer preservation of ACL-graft stability in clinical follow-up before bony incorporation.

Transformation of nortricyclane type cage compounds P4S3, P4Se3 and As4S3 by [Cp''2Zr(CO)2].

The complex [Cp''2Zr(CO)2] (Cp'' = C5H3tBu2) was used to transform the nortricyclane type cage compounds E4Q3 (E = P, Q = S, Se; E = As, Q = S) resulting in unprecedented complexes [(Cp''2Zr)2(µ,η1:1:1:1-E2Q4)] possessing bridging ligands that represent the anions of the so far unknown tetrachalcogenohypodiphosphorous acid (HQ)2PP(QH)2 and tetrathiohypodiarsenous acid (HS)2AsAs(SH)2, respectively.

Homogenized constrained mixture models for anisotropic volumetric growth and remodeling.

Constrained mixture models for soft tissue growth and remodeling have attracted increasing attention over the last decade. They can capture the effects of the simultaneous presence of multiple constituents that are continuously deposited and degraded at in general different rates, which is important to understand essential features of living soft tissues that cannot be captured by simple kinematic growth models. Recently the novel concept of homogenized constrained mixture models was introduced. It was shown that these models produce results which are very similar (and in certain limit cases even identical) to the ones of constrained mixture models based on multi-network theory. At the same time, the computational cost and complexity of homogenized constrained mixture models are much lower. This paper discusses the theory and implementation of homogenized constrained mixture models for anisotropic volumetric growth and remodeling in three dimensions. Previous constrained mixture models of volumetric growth in three dimensions were limited to the special case of isotropic growth. By numerical examples, comparison with experimental data and a theoretical discussion, we demonstrate that there is some evidence raising doubts whether isotropic growth models are appropriate to represent growth and remodeling of soft tissue in the vasculature. Anisotropic constrained mixture models, as introduced in this paper for the first time, may be required to avoid unphysiological results in simulations of vascular growth and remodeling.

[Modern networks : Topics in the working group "Bladder cancer research" of the GeSRU Academics]. / Modernes Netzwerken : Thematische Ausrichtungen in der Arbeitsgruppe "Blasenkarzinom Experimentell" der GeSRU Academics.

In January 2015, the research group "bladder cancer research" was founded as part of the GeSRU Academics research initiative. A general challenge to work successfully in a novel network structure is to identify common scientific topics and technical expertise in the group. Thus, one of the first tasks was to learn about current research projects from members within the group in order to address a project that suits the group's expertise. The following review summarizes three different directions that are key projects in Urologic Departments at German Universities that will be the basis to start fruitful collaborations.

The Role of PD-L1 Expression and Intratumoral Lymphocytes in Response to Perioperative Chemotherapy for Urothelial Carcinoma.

Introduction: Immunological pathways are relevant for the effectiveness of conventional cytotoxic chemotherapy. Recently, checkpoint inhibition of the PD-1/PD-L1 axis has been shown to be therapeutically relevant in urothelial carcinoma. Objective: To monitor PD-L1 expression on tumor cells and intratumoral infiltration with CD8 positive lymphocytes during perioperative chemotherapy for urothelial cancer and to evaluate their use as potential predictive markers for chemotherapy. Patients and Methods: Sixty-four patients with muscle-invasive urothelial cancer were included in the analysis. Twenty-two patients received preoperative chemotherapy and 42 were treated in an adjuvant setting for locally advanced disease or lymph node metastases. PD-L1 status and the density of infiltration with CD8-positive cells were assessed by immunohistochemistry and analysed for their association with survival (adjuvant group) and response to chemotherapy (preoperative group). For PD-L1 positivity we used a cutoff of 10% positive tumor cells. Results: In the adjuvant group, 11 of 42 patients (26.2%) had PD-L1 positive tumor cells. Twenty-six of 42 (61.9%) patients were highly infiltrated with CD8 + lymphocytes. There was no significant evidence of an association with overall survival for PD-L1 status nor for CD8 infiltration density (p = 0.63 and 0.71). In the preoperative group, eight of the 22 (36.4%) patients were PD-L1 positive and 13 (59%) were highly infiltrated with CD8 + lymphocytes before chemotherapy. There was no evidence of associations with response or survival. Eight patients showed a pathological response to preoperative treatment. These had a significantly longer overall survival than non-responders (p = 0.01). In the preoperative group the pre-treatment expression of the immunologic markers could be compared to the post-treatment status. Only one patient showed a changed PD-L1 status and three patients a changed CD8 status. Conclusions: The tumoral expression of PD-L1 in urothelial carcinoma does not seem to be largely influenced by chemotherapy. Our data do not provide evidence that tumoral expression of PD-L1 and CD8 are useful as prognostic or predictive markers. Small sample size is the major limitation of our study.