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Introduction Bortezomib (BTZ) is a selective and reversible proteasome inhibitor and first line treatment for multiple myeloma (MM). One of the side effects is BTZ-induced peripheral neuropathy (BIPN). Until now there is no biomarker which can predict this side effect and its severity. Neurofilament light chain (NfL) is a neuron specific cytoskeletal protein, of which higher levels can be detected in peripheral blood in case of axon damage. In this study, we aimed to evaluate the relationship between NfL serum levels and characteristics of BIPN. Methods We performed a first interim analysis of a monocentric, non-randomized, observational clinical trial including 70 patients (DRKS00025422) diagnosed with MM in the inclusion period of June 2021 until March 2022. Two groups of patients—one with ongoing BTZ treatment at the time of recruiting, and one with BTZ treatment in the past—were compared to controls. NfL in serum was analyzed via the ELLA™ device. Results Both patients with previous and ongoing BTZ treatment had higher serum NfL levels than controls, and patients with ongoing BTZ treatment had higher NfL levels than patients with BTZ treatment in the past. Serum NfL levels correlated with electrophysiological measures of axonal damage in the group with ongoing BTZ treatment. Conclusion Elevated NfL levels indicate acute axonal damage under BTZ in MM patients.

We analyzed single nucleotide polymorphisms (SNPs) in PKNOX1 (rs2839629) and in the intergenic region between PKNOX1 and CBS (rs915854) by Sanger sequencing in 88 patients with multiple myeloma treated with bortezomib. All patients (n = 13) harboring a homozygous mutation in PKNOX1 (rs2839629) also had a homozygous mutated rs915854 genotype. Homozygous mutated genotypes of rs2839629 and rs915854 were significantly enriched in patients with painful peripheral neuropathy (PNP) (P P = 0.04). In summary, both SNPs rs2839629 and/or rs915854 may be potential biomarkers predicting an increased risk to develop painful PNP under bortezomib.

Artificial Intelligence (AI) is taking centre stage in economic growth and business operations alike. Public discourse about the practical and ethical implications of AI has mainly focussed on the societal level. There is an emerging knowledge base on AI risks to human rights around data security and privacy concerns. A separate strand of work has highlighted the stresses of working in the gig economy. This prevailing focus on human rights and gig impacts has been at the expense of a closer look at how AI may be reshaping traditional workplace relations and, more specifically, workplace health and safety. To address this gap, we outline a conceptual model for developing an AI Work Health and Safety (WHS) Scorecard as a tool to assess and manage the potential risks and hazards to workers resulting from AI use in a workplace. A qualitative, practice-led research study of AI adopters was used to generate and test a novel list of potential AI risks to worker health and safety. Risks were identified after cross-referencing Australian AI Ethics Principles and Principles of Good Work Design with AI ideation, design and implementation stages captured by the AI Canvas, a framework otherwise used for assessing the commercial potential of AI to a business. The unique contribution of this research is the development of a novel matrix itemising currently known or anticipated risks to the WHS and ethical aspects at each AI adoption stage.

INTRODUCTION: Recent evidence suggests that PALB2 variants may increase risk for the development of uveal melanoma and uveal melanocytic neoplasms. Here we report a case of an atypical choroidal nevus in a patient with a personal history of cancer and pathogenic PALB2 germline variant. MATERIALS AND METHODS: Retrospective case report of a patient with an atypical choroidal nevus and pathogenic PALB2 germline variant RESULTS: A 75-year-old white female presented with an elevated predominantly amelanotic choroidal lesion OS. On examination and ophthalmic imaging, the mass measured 8.8 mm x 6.5 mm x 1.5mm. The mass showed predominantly medium to high reflectivity on diagnostic A-scan and acoustic hollowing on B-scan. OCT over the lesion showed no subretinal fluid. The patient has a personal history of breast cancer and gastric adenoma and a strong family history of cancer. The patient was found to have a pathogenic truncating variant in PALB2 (rs118203998 c.3549C>A, p.Y1183*). CONCLUSION: Together with our previous findings of pathogenic PALB2 variants in uveal melanoma patients, this new finding of an atypical choroidal nevus in a patient with a pathogenic PALB2 germline variant suggests that pathogenic PALB2 variants may be a risk factor for uveal melanocytic neoplasms. This finding warrants further assessment of the prevalence and progression of uveal melanocytic neoplasms in PALB2 pathogenic variants carriers.

Background The ability to view the posterior segment in keratoprosthesis (Kpro) implanted patients is limited. The purpose of this retrospective, observational study was to investigate the use of ultra-wide field (UWF) scanning laser ophthalmoscopy imaging and its utility for serial evaluation of the retina and optic nerve in patients with either a Boston type I or II Kpro. Methods A retrospective chart review was performed for patients with a Boston type I or II Kpro seen at The Ohio State University Wexner Medical Center. Images were graded for quality by two masked observers on a defined four-point scale (“Poor”, “Fair”, “Good”, or “Very good”) and assessed for visible posterior segment anatomy. Interobserver agreement was described using the Kappa statistic coefficient (κ) with 95% confidence intervals. Results A total of 19 eyes from 17 patients were included in this study. Eighteen eyes had a type I Kpro, while one eye had a type II Kpro. UWF imaging from 41 patient visits were reviewed by two observers. Interobserver agreement between the two graders was fair for image quality (κ = 0.36), moderate for visibility of the macula with discernible details (κ = 0.59), moderate for visibility of the anterior retina with discernable details (κ = 0.60), and perfect agreement for visibility of the optic nerve with discernible details (κ = 1.0). In 6 eyes, UWF imaging was performed longitudinally (range 3–9 individual visits), allowing for long-term follow-up (range 3–46 months) of posterior segment clinical pathology. Conclusions UWF imaging provides adequate and reliable visualization of the posterior segment in Kpro implanted patients. This imaging modality allowed for noninvasive longitudinal monitoring of retinal and optic nerve disease in this selected patient population.

Eine Weiterbildungsevaluation findet in Deutschland zum aktuellen Zeitpunkt zwar statt – allerdings nicht flachendeckend und regelmasig und ohne bundesweiten Standard. Vergleiche zwischen verschiedenen Kliniken und Ausbildern konnen daher im Moment nicht gezogen werden. Umfragemodi, wie beispielsweise in der Schweiz seit Jahrzehnten existierend, konnten eine konstruktive Grundlage in der Erhebung des aktuellen Weiterbildungsstands urologischer Assistenzarzte sein und nachfolgend die Diskussion uber Verbesserungen ermoglichen. Dazu bedarf es einer berufsgruppenubergreifenden konstruktiven Zusammenarbeit, ohne die Verantwortung lediglich den Weiterbildnern zuzuschreiben. Daruber hinaus sollten Modelle der Entlohnung guter Weiterbildung gefunden werden.

To determine the current status of surgical training amongst European Urology Residents, including their satisfaction with training and their confidence in performing procedures. A 23-item survey was distributed to the 15th European Urology Residents Education Programme (EUREP) 2017 participants. An analysis of demographics, workload, training resources, surgical exposure, surgical caseload, satisfaction and confidence in performing each procedure was performed. A total of 152/350 participants completed the survey (response rate 43%), of which 14% think they perform enough surgeries during their training, and 83% would like to continue training with a fellowship. Confidence in performing procedures without supervision and satisfaction with training was associated with higher surgical caseloads. Confidence in all laparoscopic/robotic procedures (except for laparoscopic/robotic partial nephrectomy) was associated with laparoscopic and robotics training, participation in practical courses and having training resources in hospitals. Satisfaction with surgical training was statistically associated with working ≤ 50 h per week, laparoscopic training and having laparoscopic training boxes. Surgical exposure of European Urology residents for major/minimally invasive procedures, confidence in performing these procedures, and overall satisfaction with training is low. A higher volume of cases, as well as resources for training are associated with higher individual confidence and satisfaction with training.

Die urologische Facharztausbildung steht unter der Herausforderung globaler Trends in der chirurgischen Ausbildung, den zunehmenden technologischen Entwicklungen, der Subspezialisierung des Faches und der Arbeitszeitregelungen fur Arzte. Aktuell existiert kein standardisiertes internationales Curriculum, so dass grose Unterschiede in der Ausbildung zum Facharzt fur Urologie bestehen. Das Ziel der vorliegenden Arbeit ist es, den Stand der urologischen Facharztausbildung im internationalen Vergleich abzubilden. Eine selektive Literaturrecherche wurde durchgefuhrt, um einen Uberblick uber die Vielfalt der internationalen urologischen Facharztausbildung zu geben. Hierbei wurden folgende Schlusselworter verwendet: „urology, training, residents“. Die urologische Weiterbildung in Deutschland unterliegt im Vergleich zu anderen Landern wenigen inhaltlichen, zeitlichen sowie raumlichen Vorgaben. Als wesentlicher Nachteil wird das Fehlen eines strukturierten Curriculums sowohl in Deutschland als auch in den anderen europaischen Landern angesehen. In Deutschland wird unter den Assistenzarzten neben der zunehmenden Arbeitsverdichtung die begrenzte operative Ausbildung und die fehlende Flexibilitat in der Familien- oder Forschungsplanung bemangelt. Strukturierte und validierte Kompetenzbewertungen anstatt reiner Mindestzahlen durchgefuhrter Operationen konnten die chirurgische Ausbildung verbessern. Eine objektive bundesweite Prufung als Facharztprufung ware fur ein internationales Benchmarking der Weiterbildung notwendig.

Aktuelle Erhebungen zeigen, dass sich nur 45 % der Assistenzarzte durch ihre Ausbildung ausreichend auf die urologische Tatigkeit vorbereitet fuhlen und 85 % der Weiterbildungsassistenten keinen strukturierten Weiterbildungsplan besitzen. Hinzu kommen mangelnde Transparenz, fehlende Evaluationen und okonomische Zwange zu Beginn der Weiterbildungszeit. In vielen Fallen fehlt in den weiterbildenden Kliniken eine feste Weiterbildungsstruktur. Diese Umstande geben Anlass zu einer Uberarbeitung und Reform der urologischen Weiterbildungsinhalte mit dem Ziel der Etablierung eines strukturierten Curriculums fur die urologische Facharztweiterbildung. Der vorliegende Artikel bietet einen interdisziplinaren Vergleich der deutschen urologischen Facharztweiterbildung und diskutiert mogliche Zukunftsmodelle zur Erstellung eines strukturierten Curriculums. Dazu gehoren eine bessere Definition und Koordination der Basisweiterbildung, eine Spezialisierung uber Schwerpunkte, ein funktionierendes Evaluationssystem, eine Vereinheitlichung der Prufungsinhalte sowie Freiraume fur klinische Forschung.

Subjective and objective hearing tests are used for evaluation of hearing impairments. Objective methods include impedance measurement with tympanometry and stapedius reflex measurement, otoacoustic emissions (OAE), and auditory evoked potentials (AEP). Combined with statistical analysis, the introduction of auditory steady state responses (ASSR) has enabled objective hearing tests in newborn hearing screening and automated hearing threshold assessment. The type and degree of hearing loss can be determined using the abovementioned methods. Precise interpretation of the test results is helpful to distinguish an auditory synaptopathy/neuropathy from classical sensorineural hearing loss.

Background Patients with metastatic and locally advanced bladder or prostate cancer may suffer from pelvic symptoms such as pain, obstruction, and hemorrhage. Local tumor growth is associated with significant morbidity and systemic therapy is often ineffective. Local therapies such as bladder irrigation, transurethral resection of the prostate, and fulguration of bleeding vessels provide relief but often require repeated treatments. Objectives The aim of this work was to review the current status of palliative pelvic radiotherapy for metastatic bladder and prostate cancer. Materials and methods The available literature was evaluated and treatment recommendations are proposed depending on different clinical scenarios. Results To date, no standard regimen exists for the delivery of palliative pelvic radiotherapy. Various radiotherapy schedules manage successful and long-term palliation of pelvic symptoms in most patients and result in acceptable toxicity. For bladder cancer, the most common dose and fractionation regimens range from 20 Gy in 5 fractions to 40 Gy in 20 fractions. Some retrospective studies evaluated 6 weekly fractions of 6 Gy to a total dose of 36 Gy. For prostate cancer, the most common dose and fractionation regimes range from 30 Gy in 10 fractions to 50 Gy in 25 fractions. The symptomatic response rate is between 70 and 95%. Conclusions Pelvic radiotherapy for patients with metastatic and locally advanced bladder or prostate cancer provides effective and long-term palliation of a variety of symptoms such as pain, obstruction, and hemorrhage, with acceptable toxicity. Future studies should investigate the optimal target dose and fractionation schedule.

Air conducted vestibular evoked myogenic potentials (VEMP) can be elicited by various low frequency and intense sound stimuli, mainly clicks or short tone bursts (STB). Chirp stimuli are increasingly used in diagnostic audiological evaluations as an effective means to obtain acoustically evoked responses in narrowed or extended frequency ranges. We hypothesized in this study that band limited chirp stimulation, which covers the main sensitivity range of sound sensitive otolithic afferents (around 500 Hz), might be useful for application in cervical and ocular VEMP to air conduction. For this purpose we designed a chirp stimulus ranging 250-1000 Hz (up chirp). The chirp stimulus was delivered with a stimulus intensity of 100 dB nHL in normal subjects (n = 10) and patients with otolith involvement (vestibular neuritis) (n = 6). Amplitudes of the designed chirp ("CW-VEMP-chirp, 250-1000 Hz") were compared with amplitudes of VEMPs evoked by click stimuli (0.1 ms) and a short tone burst (STB, 1-2-1, 8 ms, 500 Hz). CVEMPs and oVEMPs were detectable in 9 of 10 normal individuals. Statistical evaluation in healthy patients revealed significantly larger cVEMP and oVEMP amplitudes for CW-VEMP-chirp (250-1000 Hz) stimuli. CVEMP amplitudes evoked by CW-VEMP-chirp (250-1000 Hz) showed a high stability in comparison with click and STB stimulation. CW-VEMP-chirp (250-1000 Hz) showed abnormal cVEMP and oVEMP amplitudes in patients with vestibular neuritis, with the same properties as click and STB stimulated VEMPs. We conclude that the designed CW-VEMP-chirp (250-1000 Hz) is an effective stimulus which can be further used in VEMP diagnostic. Since a chirp stimulus can be easily varied in its properties, in particular with regard to frequency, this might be a promising tool for further investigations.

Background Fabry Disease (FD) is an X-linked hereditary lysosomal storage disorder which leads to a multisystemic intralysosomal accumulation of globotriaosylceramid (Gb3). Besides prominent renal and cardiac organ involvement, patients commonly complain about vestibulocochlear symptoms like high-frequency hearing loss, tinnitus and vertigo. However, comprehensive data especially on vertigo remain scarce. The aim of this study was to examine the prevalence and characteristics of vertigo and hearing loss in patients with FD, depending on renal and cardiac parameters and get hints about the site and the pattern of the lesions. Methods Single-center study with 57 FD patients. Every patient underwent an oto-rhino-laryngological examination as well as videonystagmography and vestibular evoked myogenic potentials (VEMPs) and audiological measurements using pure tone audiometry and auditory brainstem response audiometry (ABR). Renal function was measured by eGFR, cardiac impairment was graduated by NYHA class. Results More than one out of three patients (35.1%) complained about hearing loss, 54.4% about vertigo and 28.1% about both symptom. In 74% a sensorineural hearing loss of at least 25 dB was found, ABR could exclude any retrocochlear lesion. Caloric testing showed abnormal values in 71.9%, VEMPs were pathological in 68%. A correlation between the side or the shape of hearing loss and pathological vestibular testing could not be revealed. Conclusions Hearing loss and vertigo show a high prevalence in FD. While hearing loss seems due to a cochlear lesion, peripheral vestibular as well as central nervous pathologies cause vertigo. Thus, both the site of lesion and the pathophysiological patterns seem to differ. Electronic supplementary material The online version of this article (10.1186/s13023-018-0882-7) contains supplementary material, which is available to authorized users.

Angiogenesis in breast cancer helps fulfill the metabolic demands of the progressing tumor and plays a critical role in tumor metastasis. Therefore, various imaging modalities have been used to characterize tumor angiogenesis. While micro-CT (μCT) is a powerful tool for analyzing the tumor microvascular architecture at micron-scale resolution, magnetic resonance imaging (MRI) with its sub-millimeter resolution is useful for obtaining in vivo vascular data (e.g. tumor blood volume and vessel size index). However, integration of these microscopic and macroscopic angiogenesis data across spatial resolutions remains challenging. Here we demonstrate the feasibility of 'multiscale' angiogenesis imaging in a human breast cancer model, wherein we bridge the resolution gap between ex vivo μCT and in vivo MRI using intermediate resolution ex vivo MR microscopy (μMRI). To achieve this integration, we developed suitable vessel segmentation techniques for the ex vivo imaging data and co-registered the vascular data from all three imaging modalities. We showcase two applications of this multiscale, multi-modality imaging approach: (1) creation of co-registered maps of vascular volume from three independent imaging modalities, and (2) visualization of differences in tumor vasculature between viable and necrotic tumor regions by integrating μCT vascular data with tumor cellularity data obtained using diffusion-weighted MRI. Collectively, these results demonstrate the utility of 'mesoscopic' resolution μMRI for integrating macroscopic in vivo MRI data and microscopic μCT data. Although focused on the breast tumor xenograft vasculature, our imaging platform could be extended to include additional data types for a detailed characterization of the tumor microenvironment and computational systems biology applications.

In the past two decades advances in the development of targeted nanoparticles have facilitated their application as molecular imaging agents and targeted drug delivery vehicles. Nanoparticle-enhanced molecular imaging of the angiogenic tumor vasculature has been of particular interest. Not only because angiogenesis plays an important role in various pathologies, but also since endothelial cell surface receptors are directly accessible for relatively large circulating nanoparticles. Typically, nanoparticle targeting towards these receptors is studied by analyzing the contrast distribution on tumor images acquired before and at set time points after administration. Although several exciting proof-of-concept studies demonstrated qualitative assessment of relative target concentration and distribution, these studies did not provide quantitative information on the nanoparticle targeting kinetics. These kinetics will not only depend on nanoparticle characteristics, but also on receptor binding and recycling. In this study, we monitored the in vivo targeting kinetics of αvβ3-integrin specific nanoparticles with intravital microscopy and dynamic contrast enhanced magnetic resonance imaging, and using compartment modeling we were able to quantify nanoparticle targeting rates. As such, this approach can facilitate optimization of targeted nanoparticle design and it holds promise for providing more quantitative information on in vivo receptor levels. Interestingly, we also observed a periodicity in the accumulation kinetics of αvβ3-integrin targeted nanoparticles and hypothesize that this periodicity is caused by receptor binding, internalization and recycling dynamics. Taken together, this demonstrates that our experimental approach provides new insights in in vivo nanoparticle targeting, which may proof useful for vascular targeting in general.

The results of simulations for future measurements of electromagnetic form factors at \PANDA (FAIR) within the PandaRoot software framework are reported. The statistical precision at which the proton form factors can be determined is estimated. The signal channel $\bar p p \to e^+ e^-$ is studied on the basis of two different but consistent procedures. The suppression of the main background channel, i.e. the $\bar p p \to \pi^+ \pi^-$, is studied. Furthermore, the background versus signal efficiency, statistic and systematic uncertainties on the extracted proton form factors are evaluated using to the two different procedures. The results are consistent with those of a previous simulation study using an older, simplified framework. However, a slightly better precision is achieved in the PandaRoot study in a large range of momentum transfer, assuming the nominal beam condition and detector performances.

While the role of genetic risk factors in the etiology of uveal melanoma (UM) has been strongly suggested, the genetic susceptibility to UM is currently vastly unexplored. Due to shared epidemiological risk factors between cutaneous melanoma (CM) and UM, in this study we have selected 28 SNPs identified as risk variants in previous genome-wide association studies on CM or CM-related host phenotypes (such as pigmentation and eye color) and tested them for association with UM risk. By logistic regression analysis of 272 UM cases and 1782 controls using an additive model, we identified five variants significantly associated with UM risk, all passing adjustment for multiple testing. The three most significantly associated variants rs12913832 (OR = 0.529, 95% CI 0.415–0.673; p = 8.47E-08), rs1129038 (OR = 0.533, 95% CI 0.419–0.678; p = 1.19E-07) and rs916977 (OR = 0.465, 95% CI 0.339–0.637; p = 3.04E-07) are correlated (r2 > 0.5) and map at 15q12 in the region of HERC2/OCA2, which determines eye-color in the human population. Our data provides first evidence that the genetic factors associated with pigmentation traits are risk loci of UM susceptibility.

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