Search

This study was intended to describe the application of Discovery Learning Model on natural science subject and to improve teacher’s skill and learning result of student on fifth grade of Elementary School. This research was classroom action research conducted in two cycles. Each cycle consists of planning, action, observation and reflection. Subjects of this research were students at fifth grade of SD Katolik St. Paulus Kembes. The collecting data technique was using test and observation. Technique of analyzing data was using quantitive descriptive analysis and qualitative descriptive analysis. The results showed that: 1) teacher’s skill in first cycle gained score 25 or 71,42% with ‘good’ criteria, and in second cycle obtained score 29 or 82,85% also with ‘good’ criteria; 2) student’s learning result in first cycle was 62,2% and the second cycle was 81,6%. These results concluded that the application of Discovery Learning Model can improve the quality of natural science subject learning, such as: teacher’s skill and learning result of the fifth grade student in SD Katolik St. Paulus Kembes. It was suggested that Discovery Learning model can be used as teacher’s solution to improve the quality of natural science learning.

PURPOSE: The proPSMA trial at ten Australian centers demonstrated increased sensitivity and specificity for PSMA PET/CT compared to conventional imaging regarding metastatic status in primary high-risk prostate cancer patients. A cost-effectiveness analysis showed benefits of PSMA PET/CT over conventional imaging for the Australian setting. However, comparable data for other countries are lacking. Therefore, we aimed to verify the cost-effectiveness of PSMA PET/CT in several European countries as well as the USA. METHODS: Clinical data on diagnostic accuracy were derived from the proPSMA trial. Costs for PSMA PET/CT and conventional imaging were taken from reimbursements of national health systems and individual billing information of selected centers in Belgium, Germany, Italy, the Netherlands, and the USA. For comparability, scan duration and the decision tree of the analysis were adopted from the Australian cost-effectiveness study. RESULTS: In contrast to the Australian setting, PSMA PET/CT was primarily associated with increased costs in the studied centers in Europe and the USA. Mainly, the scan duration had an impact on the cost-effectiveness. However, costs for an accurate diagnosis using PSMA PET/CT seemed reasonably low compared to the potential consequential costs of an inaccurate diagnosis. CONCLUSION: We assume that the use of PSMA PET/CT is appropriate from a health economic perspective, but this will need to be verified by a prospective evaluation of patients at initial diagnosis.

Purpose: This study aims to address therapy-related toxicities and quality of life in prostate cancer patients undergoing transperineal ultrasound (TPUS) guided radiotherapy (RT). Methods: Acute and late gastrointestinal (GI) and genitourinary (GU) toxicities were assessed by physicians using CTCAE v5.0. Patient-reported quality of life outcomes were evaluated using EORTC QLQ-C30, -PR25 and IPSS. We utilized Volumetric Modulated Arc Therapy (VMAT) or intensity modulated radiation therapy (IMRT) as the RT technique for this study. The assessments were carried out before RT, at RT end, 3 months after RT and subsequently at 1-year intervals. Prostate-specific antigen (PSA) was also evaluated at each follow-up. Results: In this study, a total of 164 patients were enrolled, while among them, 112 patients delivered quality-of-life data in a prospective evaluation. The median pre-treatment PSA was 7.9 ng/mL (range: 1.8–169 ng/ml). At the median follow-up of 19 months (3–82 months), the median PSA decreased to 0.22 ng/ml. Acute grade II GI and GU toxicities occurred in 8.6 % and 21.5 % patients at RT end. Regarding late toxicities, 2.2 % patients experienced grade II GI toxicities at 27 months and only one patient at 51 months, whereas no grade II GU late toxicities were reported at these time points. Quality of life scores also indicated a well-tolerated treatment. Patients mainly experienced acute clinically relevant symptoms of fatigue, pain, as well as deterioration in bowel and urinary symptoms. However, most symptoms normalized at 3 months and remained stable thereafter. Overall functioning showed a similar decline at RT end but improved over time. Conclusion: The outcomes of TPUS-guided RT demonstrated promising results in terms of minimal physician-reported toxicities and satisfactory patient-reported QoL.

IntroductionMirabegron is available for treatment of overactive bladder (OAB). However, mechanisms underlying symptom improvements and long-term effects on bladder smooth muscle cells are uncertain. Contractility and growth of bladder smooth muscle contribute to OAB, and depend on smooth muscle phenotypes, and on muscarinic receptor expression. Here, we examined prolonged exposure to mirabegron (20–48 h) on phenotype markers, muscarinic receptor expression, and phenotype-dependent functions in human bladder smooth muscle cells (hBSMC).MethodsExpression of markers for contractile (calponin, MYH11) and proliferative (MYH10, vimentin) phenotypes, proliferation (Ki-67), and of muscarinic receptors were assessed by RT-PCR. Proliferation, viability, actin organization and contractions in cultured hBSMC were examined by EdU, CCK-8, phalloidin staining and matrix contraction assays.ResultsCalponin-1 mRNA decreased with 100 nM and 150 nM mirabegron applied for 20 h (0.56–0.6 fold of controls). Decreases were resistant to the β3-AR antagonist L-748,337 (0.34–0.55 fold, 100–150 nM, 20 h). After 40 h, decreases occured in the presence of L-748,337, but not without L-748,337. MYH11 mRNA increased with 150 nM mirabegron (40 h, 1.9 fold). This was partly preserved with L-748,337, but not observed after 20 h mirabegron exposure. Vimentin mRNA reduced with 150 nM mirabegron after 20 h, but not after 40 h, with and without L-748,337 (0.71–0.63 fold). MYH10 mRNA expression remained unaffected by mirabegron. Exposure to 150 nM mirabegron increased Ki-67 mRNA after 20 h in the presence of, but not without L-748,337, and after 40 h without, but not with L-748,337. Proliferation rates and actin organization were stable with 50–150 nM mirabegron (24 h, 48 h). Viability increased significantly after mirabegron exposure for 20 h, and by trend after 40 h, which was fully sensitive to L-748,337. M2 mRNA was reduced by 20 h mirabegron, which was resistant to L-748,337. Carbachol (3 µM) enhanced time-dependent contractions of hBSMC, which was inhibited by mirabegron (150 nM) in late phases (24 h), but not in early phases of contractions.Conclusion: Mirabegron induces dynamic phenotype alterations and M2 downregulation in hBSMC, which is paralleled by time-shifted anticontractile effects. Phenotype transitions may be involved in improvements of storage symptoms in OAB by mirabegron.

BackgroundDue to improved imaging sensitivity, the term "oligometastatic" prostate cancer disease is diagnosed more often, leading to an increasing interest in metastasis-directed therapy (MDT). There are two types of radiation based MDT applied when treating oligometastatic disease: (1) stereotactic body radiation therapy (SBRT) generally used for bone metastases; or (2) SBRT for isolated nodal oligometastases combined with prophylactic elective nodal radiotherapy. This review aims to summarize current evidence data, which may shed light on the optimal management of this heterogeneous group of patients.MethodsA systematic review of the Medline database through PubMed was performed according to PRISMA guidelines. All relevant studies published up to November 2020 were identified and screened. Fifty-six titles were included. Besides outcome parameters, different prognostic and predictive factors were assessed, including site of metastases, time between primary treatment and MDT, use of systemic therapies, hormone sensitivity, as well as pattern of recurrence.FindingsEvidence consists largely of retrospective case series and no consistent precise definition of oligometastasis exists, however, most investigators seem to acknowledge the need to distinguish between patients presenting with what is frequently called "synchronous" versus "metachronous" oligometastatic disease. Available data on radiotherapy as MDT demonstrate high local control rates and a small but relevant proportion of patients without progressive disease after 2 years. This holds true for both hormone sensitive and castration resistant prostate cancer diseases. The use of 68Ga-PSMA PET/CT for staging increased dramatically. Radiation doses and field sizes varied considerably among the studies. The search for relevant prognostic and predictive factors is ongoing.ConclusionsTo our best knowledge this review on oligometastatic prostate cancer included the largest number of original articles. It demonstrates the therapeutic potential and challenges of MDT for oligometastatic prostate cancer. Prospective studies are under way and will provide further high-level evidence.

Aims: Accurate skeletal age and final adult height prediction methods in paediatric orthopaedics are crucial for determining optimal timing of growth-guiding interventions and minimizing complications in treatments of various conditions. This study aimed to evaluate the accuracy of final adult height predictions using the central peak height (CPH) method with long leg X-rays and four different multiplier tables. Methods: This study included 31 patients who underwent temporary hemiepiphysiodesis for varus or valgus deformity of the leg between 2014 and 2020. The skeletal age at surgical intervention was evaluated using the CPH method with long leg radiographs. The true final adult height (FHTRUE) was determined when the growth plates were closed. The final height prediction accuracy of four different multiplier tables (1. Bayley and Pinneau; 2. Paley et al; 3. Sanders – Greulich and Pyle (SGP); and 4. Sanders – peak height velocity (PHV)) was then compared using either skeletal age or chronological age. Results: All final adult height predictions overestimated the FHTRUE, with the SGP multiplier table having the lowest overestimation and lowest absolute deviation when using both chronological age and skeletal age. There were no significant differences in final height prediction accuracy between using skeletal age and chronological age with PHV (p = 0.652) or SGP multiplier tables (p = 0.969). Adult height predictions with chronological age and SGP (r = 0.769; p ≤ 0.001), as well as chronological age and PHV (r = 0.822; p ≤ 0.001), showed higher correlations with FHTRUE than predictions with skeletal age and SGP (r = 0.657; p ≤ 0.001) or skeletal age and PHV (r = 0.707; p ≤ 0.001). Conclusion: There was no significant improvement in adult height prediction accuracy when using the CPH method compared to chronological age alone. The study concludes that there is no advantage in routinely using the CPH method for skeletal age determination over the simple use of chronological age. The findings highlight the need for more accurate methods to predict final adult height in contemporary patient populations. Cite this article: Bone Jt Open 2023;4(10):750–757.

Abstract In the hadal zone of the ocean (6–11 km), the characteristics of sinking marine snow particles and their attached microbial communities remain elusive, despite their potential importance for benthic life thriving at extreme pressures (60–110 MPa). Here, we used simulation experiments to explore how increasing pressure levels modify the microbial degradation, organic matter composition, and microbiome of sinking diatom aggregates. Individual aggregates were incubated in rotating tanks in which pressure was incrementally increased to simulate a descent from surface to hadal depth within 20 days. Incubations at atmospheric pressure served as controls. With increasing pressure, microbial respiration and diatom degradation decreased gradually and ceased completely at 60 MPa. Dissolved organic carbon leaked substantially from the aggregates at ≥40 MPa, while diatom lipid and pigment contents decreased moderately. Bacterial abundance remained stable at >40 MPa, but bacterial community composition changed significantly at 60–100 MPa. Thus, pressure exposure reduces microbial degradation and transforms both organic matter composition and microbiomes of sinking particles, which may seed hadal sediments with relatively fresh particulate organic matter and putative pressure-tolerant microbes.

Digital therapeutics (DTx) are a new class of intervention involving evidence-based software applications and have been used in neurology and psychiatry. To assess the potential of DTx in urology, we conducted a survey to assess the current prevalence of the digital infrastructure required for DTx, areas of support expected by patients, and requirements for uptake. Between November 2022 and January 2023, we conducted an anonymized survey at two German academic centers among patients with urologic conditions. We found that among patients aged

BackgroundSynovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCL) are ideal solid tumors for the development of adoptive cellular therapy (ACT) targeting NY-ESO-1, as a high frequency of tumors homogeneously express this cancer-testes antigen. Data from early phase clinical trials have shown antitumor activity after the adoptive transfer of NY-ESO-1-specific T cells. In these studies, persistence of NY-ESO-1 specific T cells is highly correlated with response to ACT, but patients often continue to have detectable transferred cells in their peripheral blood following progression.MethodWe performed a phase I clinical trial evaluating the safety of NY-ESO-1-specific endogenous T cells (ETC) following cyclophosphamide conditioning. Peripheral blood mononuclear cells (PBMCs) from treated patients were evaluated by flow cytometry and gene expression analysis as well as through ex vivo culture assays with and without IL-15.ResultsFour patients were treated in a cohort using ETC targeting NY-ESO-1 following cyclophosphamide conditioning. Treatment was well tolerated without significant toxicity, but all patients ultimately had disease progression. In two of four patients, we obtained post-treatment tumor tissue and in both, NY-ESO-1 antigen was retained despite clear detectable persisting NY-ESO-1-specific T cells in the peripheral blood. Despite a memory phenotype, these persisting cells lacked markers of proliferation or activation. However, in ex vivo culture assays, they could be induced to proliferate and kill tumor using IL-15. These results were also seen in PBMCs from two patients who received gene-engineered T-cell receptor-based products at other centers.ConclusionsETC targeting NY-ESO-1 with single-agent cyclophosphamide alone conditioning was well tolerated in patients with SS and those with MRCL. IL-15 can induce proliferation and activity in persisting NY-ESO-1-specific T cells even in patients with disease progression following ACT. These results support future work evaluating whether IL-15 could be incorporated into ACT trials post-infusion or at the time of progression.

Abstract Introduction As a high-quality TUR-BT is important to ensure adequate treatment for bladder cancer patients, the aim of the current study is to investigate the impact of patient-related, surgical and tumor-specific parameters on detrusor muscle (DM) absence (primary objective) and to assess the impact of DM on the prognosis after a TUR-BT (secondary objective). Patients and methods Transurethral resection of bladder tumors (TUR-BTs) between 2009 and 2021 were retrospectively screened (n = 3237). We included 2058 cases (1472 patients) for the primary and 472 patients for secondary objective. Clinicopathological variables including tumor size, localization, multifocality, configuration, operation time and skill-level of the urologist were assessed. We analyzed predictors for missing DM and prognostic factors for recurrence-free survival (RFS) for the complete cohort and subgroups. Results DM was present in 67.6% (n = 1371/2058). Surgery duration (continuous, minutes) was an independent predictor for absence of DM in the complete cohort (OR:0.98, r:0.012, 95%CI:0.98–0.99, p = 0.001). Other significant risk factors for missing DM were papillary tumors (OR:1.99, r:0.251, 95%CI:1.22–3.27, p = 0.006) in the complete cohort and bladder-roof and posterior-bladder-wall localization for re-resections. Absence of DM in high-grade BC correlated with reduced RFS (HR:1.96, 95%CI:1.0–3.79, p = 0.045). Conclusion Sufficient time for a TUR-BT is mandatory to assure DM in the TUR-BT specimen. Also, cases with more difficult locations of bladder tumors should be performed with utmost surgical diligence and endourological training should incorporate how to perform such operations. Of note, DM correlates with improved oncological prognosis in high-grade BC.

BackgroundThe onset of the COVID-19 pandemic in the United States in March 2020 caused a dramatic change in the way many people lived. Few aspects of daily life were left undisrupted by the pandemic’s onset as well as the accompanying policies to control the spread of the disease. Previous research has found that the pandemic may have significantly impacted the mental health of lesbian, gay, bisexual, transgender, and queer (LGBTQ) individuals—potentially more so than other individuals. However, the pandemic did not affect all areas of the United States at the same time, and there may be regional variation in the impact of the onset of the pandemic on depressive symptoms among LGBTQ individuals. ObjectiveTo assess regional variation of the impact of the pandemic, we conducted a time series analysis stratified by US geographic region to examine symptoms of depression and anxiety among a sample of primarily cisgender gay and bisexual men before and after the onset of the COVID-19 pandemic in the United States. MethodsIn total, 5007 participants completed assessments as part of the Together 5000 study, an ongoing prospective cohort study. Depressive and anxiety symptoms were measured using the Patient Health Questionnaire-4. Patient Health Questionnaire-4 scores were graphed as a function of days from March 15, 2020. Locally estimated scatterplot smoothing trend lines were applied. A sieve-bootstrap Mann-Kendall test for monotonic trend was conducted to assess the presence and direction of trends in the scatterplots. We then compared the observed trends to those observed for 1 year prior (2018-2019) to the pandemic onset using data collected from the same sample. ResultsSignificant positive trends were detected for the Northeast (P=.03) and Midwest (P=.01) regions of the United States in the 2020 assessment, indicating that symptoms of anxiety and depression were increasing in the sample in these regions immediately prior to and during the onset of the pandemic. In contrast, these trends were not present in data from the 2018 to 2019 assessment window. ConclusionsSymptoms of anxiety and depression increased among the study population in the Northeast and Midwest during the beginning months of the COVID-19 pandemic, but similar increase was not observed in the South and West regions. These trends were also not found for any region in the 2018 to 2019 assessment window. This may indicate region-specific trends in anxiety and depression, potentially driven by the burden of the pandemic and policies that varied from region to region. Future studies should consider geographic variation in COVID-19 spread and policies as well as explore potential mechanisms by which this could influence the mental health of LGBTQ individuals.

Abstract Objective To evaluate the relationship between pre‐operative PSA value, 68Ga‐prostate‐specific‐membrane‐antigen (PSMA) PET performance and oncologic outcomes after salvage lymph node dissection (sLND) for biochemical recurrent prostate cancer (PCa). Patients and methods The study included 164 patients diagnosed with ≤2 pelvic lymph‐node recurrence(s) of PCa documented on 68Ga‐PSMA PET scan and treated with pelvic ± retroperitoneal sLND at 11 high‐volume centres between 2012 and 2019. Pathologic findings were correlated to PSA values at time of sLND, categorized in early (1.5 ng/ml). Clinical recurrence (CR)‐free survival after sLND was calculated using multivariable analyses and plotted over pre‐operative PSA value. Results Median [interquartile range (IQR)] PSA at sLND was 1.1 (0.6, 2.0) ng/ml, and 131 (80%) patients had one positive spot at PET scan. All patients received pelvic sLND, whereas 91 (55%) men received also retroperitoneal dissection. Median (IQR) number of node removed was 15 (6, 28). The rate of positive pathology increased as a function of pre‐operative PSA value, with highest rates for patients with pre‐operative PSA > 1.5 ng/ml (pelvic‐only sLNDs: 84%; pelvic + retroperitoneal sLNDs: 90%). After sLND, PSA ≤ 0.3 ng/ml was detected in 67 (41%) men. On multivariable analyses, pre‐operative PSA was associated with PSA response (p

Radar target simulators are not only a critical tool for verifying and testing radar systems but also play an important role in supporting the development of self-driving cars. Advances in radar sensors and techniques raise the required specifications for these units, increasing their complexity and cost. This article presents a novel and universal concept for radar target simulators that addresses these issues by responding only to the transmitted signal of a radar sensor during a fraction of the time, therefore modulating the average of the signal. This offers advantages for three independent use cases, which may be combined. First, the dynamic range and resolution of simulated target echo power can be improved even for existing systems. Second, the simulation of multiangle scenarios with a single backend is possible with this approach. Finally, hardware complexity and power consumption can be reduced. The proposed concept is examined extensively for frequency-modulated continuous wave radar, and design decisions are made. The theoretical considerations are validated with measurements with a real radar target simulator showing an improvement of up to $30 \,\mathrm{dB}$ in the dynamic range with no observable negative side effects.

Alexander Tamalunas,1 Philipp Lenau,1 Leo Federico Stadelmeier,1 Jan-Niclas Mumm,1 Theresa Vilsmaier,2 Henrik Höhn,2 Maja-Lena Mumm,3 Raphaela Waidelich,1 Jozefina Casuscelli,1 Giuseppe Magistro,1 Alexander Buchner,1 Thomas Kolben,2 Christian Stief,1 Martin Hennenberg1 1Department of Urology, University Hospital, LMU Munich, Munich, Germany; 2Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Munich, Germany; 3Department of Political and Social Sciences, Institute for Media and Communication Studies, Freie Universität Berlin, Berlin, GermanyCorrespondence: Alexander Tamalunas, Department of Urology, University Hospital, LMU Munich, Marchioninistr. 15, Munich, 81377, Germany, Tel +49 89 4400 – 0, Email alexander.tamalunas@med.uni-muenchen.dePurpose: The present study aimed to investigate the influence of patients’ and urologists’ gender when choosing a urologist. With rising population diversity through immigration and generational differences, patient-centered healthcare has recently moved to the focus of European healthcare systems. As healthcare in urology often concentrates on sensitive topics, and often involves gender-specific diseases, research on the influence of gender on decision-making processes is of high importance. Understanding influence of gender on patients’ choices in real life would provide patients, and physicians alike, with the means to provide better resources to achieve greater satisfaction from visits to a urologist.Patients and Methods: A questionnaire was prepared, and patients at our tertiary referral center were given the opportunity to voluntarily participate in our survey. We collected questionnaires from 1012 patients during their visits from June 2021 to October 2021.Results: Patients were divided into groups according to their gender: male (n=763), female (n=246), and non-binary (n=3). Our patient cohort consisted of more men than women (75% vs 24%), with only three patients identifying as non-binary. Irrespective of the patients’ own gender, patients preferred a male urologist when problems were considered embarrassing, limiting daily activities, or when worrisome. When problems were considered painful, all patients preferred a female urologist. When patients had had a previous positive experience with a female or male urologist, they preferred to be treated by a female or male urologist, respectively. Overall, 65% of patients stated a gender preference for at least one given situation, or consultation scenario.Conclusion: As the majority of our patients stated a gender preference, urological departments should be considerate of potential patients’ preferences for urologist gender that may be based on the individual patient’s history, taking a comprehensive approach to fulfill the patients’ need for same gender urologists in educational hospitals and health care services.Keywords: gender, sex, urologist, health economics, health services research, medical research, patient-centered care, person-centered medicine, public health, decision making

In addition to general anesthesia and mechanical ventilation, robotic-assisted laparoscopic radical prostatectomy (RALP) necessitates maintaining a capnoperitoneum and placing the patient in a pronounced downward tilt (Trendelenburg position). While the effects of the resulting fluid shift on the cardiovascular system seem to be modest and well tolerated, the effects on the brain and the blood–brain barrier have not been thoroughly investigated. Previous studies indicated that select patients showed an increase in the optic nerve sheath diameter (ONSD), detected by ultrasound during RALP, which suggests an elevation in intracranial pressure. We hypothesize that the intraoperative fluid shift results in endothelial dysfunction and reduced cerebral clearance, potentially leading to transient neuronal damage. This prospective, monocentric, non-randomized, controlled clinical trial will compare RALP to conventional open radical prostatectomy (control group) in a total of 50 subjects. The primary endpoint will be the perioperative concentration of neurofilament light chain (NfL) in blood using single-molecule array (SiMoA) as a measure for neuronal damage. As secondary endpoints, various other markers for endothelial function, inflammation, and neuronal damage as well as the ONSD will be assessed. Perioperative stress will be evaluated by questionnaires and stress hormone levels in saliva samples. Furthermore, the subjects will participate in functional tests to evaluate neurocognitive function. Each subject will be followed up until discharge. Conclusion: This trial aims to expand current knowledge as well as to develop strategies for improved monitoring and higher safety of patients undergoing RALP. The trial was registered with the German Clinical Trials Register DRKS00031041 on 11 January 2023.

Abstract Background Nectin-4 contributes to tumor proliferation, lymphangiogenesis and angiogenesis in malignant tumors and is an emerging target in tumor therapy. In renal cell carcinoma (RCC) VEGF-directed tyrosine kinase inhibitors and checkpoint inhibitors are currently treatments of choice. Enfortumab vedotin-ejf (EV) is an antibody drug conjugate that targets Nectin-4. The aim of our study was to investigate the expression of Nectin-4 in a large cohort of papillary RCC specimens. Patients and methods Specimens were derived from the PANZAR consortium (Erlangen, Heidelberg, Herne, Homburg, Mainz, Mannheim, Marburg, Muenster, LMU Munich, TU Munich, and Regensburg). Clinical data and tissue samples from n = 190 and n = 107 patients with type 1 and 2 pRCC, respectively, were available. Expression of Nectin-4 was determined by immunohistochemistry (IHC). Results In total, Nectin-4 staining was moderately or strongly positive in of 92 (48.4%) of type 1 and 39 (36.4%) type 2 of pRCC cases. No associations between Nectin-4 expression and age at diagnosis, gender, grading, and TNM stage was found. 5 year overall survival rate was not statistically different in patients with Nectin-4 negative versus Nectin-4 positive tumors for the overall cohort and the pRCC type 2 subgroup, but higher in patient with Nectin-4 positive pRCC type 1 tumors compared to Nectin-4 negative tumors (81.3% vs. 67.8%, p = 0.042). Conclusion Nectin-4 could not be confirmed as a prognostic marker in pRCC in general. Due to its high abundance on pRCC specimens Nectin-4 is an interesting target for therapeutical approaches e.g. with EV. Clinical trials are warranted to elucidate its role in the pRCC treatment landscape.

Severin Rodler,1 Alexander Buchner,1 Lennert Eismann,1 Gerald Bastian Schulz,1 Julian Marcon,1 Stephan Ledderose,2 Boris Schlenker,1 Christian G Stief,1 Alexander Karl,3 Jan-Friedrich Jokisch1 1Department of Urology, Klinikum der Universität München, Munich, Germany; 2Department of Pathology, Klinikum der Universität München, Munich, Germany; 3Department of Urology, Barmherzige Brüder Krankenhaus München, Munich, GermanyCorrespondence: Severin Rodler, Department of Urology, Klinikum der Universität München, Marchioninistr. 15, München, 81377, Germany, Tel +089 4400 73530, Fax +089 4400 76532, Email severin.rodler@med.uni-muenchen.dePurpose: Absence of tumor in the final histopathology after radical cystectomy (RC) is a rare but potentially favorable outcome. Therefore, we aimed to analyze outcomes and prognostic factors of patients with urothelial carcinoma (UC) undergoing RC and T0 in the final histology without neoadjuvant chemotherapy at a high-volume academic center.Patients and Methods: We retrospectively analyzed patients undergoing RC for pure UC between 2004 and 2020. Cancer-specific survival (CSS) and overall survival (OS) were calculated using Kaplan–Meier analysis and group comparison by Log rank test. Potential prognostic factors were analyzed using univariate Cox regression models.Results: A total of 1051 patients with UC underwent RC. 72 patients (6.7%) showed pT0 in the final histology. Across all T-stages, 5-year CSS was significantly different with 88% for pT0, 80% for pTa/pTis, 78% for pT1, 76% for pT2, 51% for pT3 and 27% for pT4 in our cohort (p=0.001). Neither instillation therapy (HR 0.31, 95% CI 0.07– 1.43), number of TURB prior RC (HR 1.47, 95% CI 0.25– 6.18), use of photodynamic diagnostics (PDD) (HR 0.64, 95% CI 0.14– 3.02), performing a second resection (HR 0.87, 95% CI 0.27– 2.86), muscle-invasive disease prior RC at any TURB (HR 0.7, 95% CI 0.2– 2.39) or muscle-invasive disease in the TURB prior RC (HR 1.0, 0.31– 3.29) were associated with CSS in univariate analysis.Conclusion: pT0 reveals a survival benefit in patients undergoing RC for UC and therefore presents a distinctive tumor entity. As clinical and cystoscopic characteristics do not improve patient stratification, further research is warranted to define risk groups in this specific tumor entity.Keywords: bladder cancer, radical cystectomy, pT0 status after cystectomy

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac, belong to the most prescribed analgesic medication after traumatic injuries. However, there is accumulating evidence that NSAIDs impair fracture healing. Because bone regeneration in aged patients is subject to significant changes in cell differentiation and proliferation as well as a markedly altered pharmacological action of drugs, we herein analyzed the effects of diclofenac on bone healing in aged mice using a stable closed femoral facture model. Thirty-three mice (male n = 14, female n = 19) received a daily intraperitoneal injection of diclofenac (5 mg/kg body weight). Vehicle-treated mice (n = 29; male n = 13, female n = 16) served as controls. Fractured mice femora were analyzed by means of X-ray, biomechanics, micro computed tomography (μCT), histology and Western blotting. Biomechanical analyses revealed a significantly reduced bending stiffness in diclofenac-treated animals at 5 weeks after fracture when compared to vehicle-treated controls. Moreover, the callus tissue in diclofenac-treated aged animals exhibited a significantly reduced amount of bone tissue and higher amounts of fibrous tissue. Further histological analyses demonstrated less lamellar bone after diclofenac treatment, indicating a delay in callus remodeling. This was associated with a decreased number of osteoclasts and an increased expression of osteoprotegerin (OPG) during the early phase of fracture healing. These findings indicate that diclofenac delays fracture healing in aged mice by affecting osteogenic growth factor expression and bone formation as well as osteoclast activity and callus remodeling.

Osteoarthritis of the hip is a common condition that affects older adults. Total hip replacement is the end-stage treatment to relief pain and improve joint function. Little is known about the mechanical load distribution during the activity of bipedal stance, which is an important daily activity for older adults who need to rest more frequently. This study investigated the distribution of the hip and knee joint moments during bipedal stance in patients with unilateral hip osteoarthritis and how the distribution changed 1 year after total hip replacement. Kinematic and kinetic data from bipedal stance were recorded. External hip and knee adduction moments were calculated and load distribution over both limbs was calculated using the symmetry angle. Preoperatively, the non-affected limb carried 10% more body weight than the affected limb when standing on two legs. Moreover, the mean external hip and knee adduction moments of the non-affected limb were increased compared to the affected limb. At follow-up no significant differences were observed between the patients’ limbs. Preoperative and postoperative changes in hip adduction moment were mainly explained by the combination of the vertical ground reaction force and the hip adduction angle. Stance width also explained changes in the hip and knee adduction moments of the affected leg. Furthermore, as with walking, bipedal standing also showed an asymmetric mechanical load distribution in patients with unilateral hip osteoarthritis. Overall, the findings suggest the need for preventive therapy concepts that focus not only on walking but also on optimizing stance towards a balanced load distribution of both legs.

Introduction: Correction of knee malalignment by guided growth using a tension-band plate is a common therapy to prevent knee osteoarthritis among other things. This approach is based on the Hueter-Volkmann law stating that the length growth of bones is inhibited by compression and stimulated by tension. How the locally varying mechanical loading of the growth plate is influenced by the implant has not yet been investigated. This study combines load cases from the gait cycle with personalized geometry in order to investigate the mechanical influence of the tension-band plates.Methods: Personalized finite element models of four distal femoral epiphyses of three individuals, that had undergone guided growth, were generated. Load cases from the gait cycles and musculoskeletal modelling were simulated with and without implant. Morphological features of the growth plates were obtained from radiographs. 3D geometries were completed using non-individual Magnetic Resonance Images of age-matched individuals. Boundary conditions for the models were obtained from instrumented gait analyses.Results: The stress distribution in the growth plate was heterogenous and depended on the geometry. In the insertion region, the implants locally induced static stress and reduced the cyclic loading and unloading. Both factors that reduce the growth rate. On the contralateral side of the growth plate, increased tension stress was observed, which stimulates growth.Discussion: Personalized finite element models are able to estimate the changes of local static and cyclic loading of the growth plate induced by the implant. In future, this knowledge can help to better control growth modulation and avoid the return of the malalignment after the treatment. However, this requires models that are completely participant-specific in terms of load cases and 3D geometry.

The accumulation and storage of nitrate by diatoms can contribute up to 1% of total pelagic nitrate and as much as 95% of total benthic nitrate, which indicates a potentially important contribution of diatoms to benthic nitrogen cycling, according to a global analysis

Introduction/Objective: Contrast-enhanced ultrasound (CEUS) is a promising modality for differentiating benign and malignant lesions in various organs, including the testis. Testicular tumors, common in young men, are often treated with radical orchiectomy, which can have significant consequences. This study aimed to analyze CEUS parameters and their association with malignant testicular tumors. Materials and Methods: Between May 2009 and September 2020, 342 patients with suspected testicular lesions underwent CEUS at a tertiary referral center. Multiparametric ultrasound, including B-mode, Color Doppler, CEUS, and elastography, was performed. Exclusion criteria were the absence of a testicular lesion in the CEUS examination. Histological results, CEUS parameters, and elastography data were analyzed, and statistical correlations were evaluated using chi-square and Mann–Whitney U tests, with multivariate logistic regression for significant findings. Results: Of the 342 patients, 114 (33.3%) had suspicious CEUS findings, and 84 underwent surgical exploration. Malignancy was confirmed in 48 cases (57.1%). The sensitivity and specificity of CEUS for detecting malignancy were 93.8% and 85.2%, respectively. Contrast enhancement was observed in 93.3% of malignant tumors, but not statistically significant compared to benign lesions (p = 0.107). However, elastography revealed higher tissue stiffness in 77.8% of malignant tumors versus 41.0% in benign lesions (p = 0.009). Multivariate analysis indicated that tissue stiffness was significantly associated with malignancy (HR 8.29, 95%CI 1.26–54.58, p = 0.028). Conclusions: CEUS is a valuable tool for testicular lesion evaluation, with elastography showing strong potential in predicting malignancy through tissue stiffness. However, contrast enhancement and "wash-in/-out" were not reliable malignancy indicators. Further research is needed to standardize CEUS and elastography techniques for routine clinical use. [ABSTRACT FROM AUTHOR]

Introduction: Higher intraoperative opioid doses may be associated with worse long-term oncological outcomes after radical prostatectomy (RP) for prostate cancer. We aimed to evaluate the impact of higher doses of intraoperative opioids and type of anesthesia on biochemical recurrence (BCR) and mortality after RP in a high-volume tertiary center. Methods: All patients underwent RP at our center between 2015 and 2021. The role of major intraoperative opioid agents, such as sufentanil remifentanil, and morphine milligram equivalents (MMEs), as well as the type of anesthesia [total intravenous anesthesia (TIVA), versus a combination of TIVA and epidural anesthesia, versus solely epidural anesthesia], was assessed in predicting BCR and survival after RP. Results: A total of 1137 patients who had a median age of 66 years (interquartile range: 61–72) were included. Overall, 1062 (93%) patients received TIVA, 37 (3%) received TIVA and epidural anesthesia, and 41 (4%) only epidural anesthesia. At a median follow-up of 431 days (interquartile range: 381–639) from RP, 257 (24%) patients developed a BCR. Accordingly, at a median follow-up of 500 days (interquartile range: 450–750), 33 (2.9%) patients died. The type of anesthesia, as well as the dosage or type of the selected intraoperative opioid agents, did not affect either BCR or long-term overall survival. Conclusions: These findings suggest that intraoperative opioid application during RP has no negative oncological impact in the short and long term in patients with localized prostate cancer. Accordingly, combined TIVA and epidural anesthesia, as well as solely epidural anesthesia were associated with similar short- and long-term outcomes compared to TIVA. [ABSTRACT FROM AUTHOR]

Simple Summary: Worldwide, prostate cancer is the second most common cancer affecting men. Both the disease and treatments like surgery, radiotherapy, or drug therapy can cause unpleasant side effects, such as fatigue, muscle loss, and reduced quality of life. Exercise, particularly strength training and aerobic workouts, has been suggested to help reduce these effects. This study reviewed findings from controlled trials to evaluate how strength training, aerobic exercise, or a combination of both, affected men receiving prostate cancer treatment. The results show that combining strength and aerobic exercise significantly improves quality of life, especially in general health, mental clarity, and sexual wellbeing. Strength training alone helped by increasing muscle mass and lowering body fat. Both types of exercise improved physical strength and fitness. However, the training had no impact on laboratory results like PSA or cholesterol levels. More research is needed on long-term effects, particularly of aerobic exercise alone. Background: Prostate cancer (PC) and its treatment are often associated with side effects such as fatigue, muscle loss, and diminished quality of life (QoL). Physical exercise, particularly resistance training (RT) and aerobic training (AT), has been suggested as a strategy to mitigate these effects. However, the comparative efficacy of RT, AT, and combined RT/AT on QoL, body composition, physical fitness, and laboratory markers in PC patients is still insufficiently understood. Methods: Randomized controlled trials (RCTs) investigating structured RT, AT, or combined RT/AT programs in PC patients undergoing various treatments were included. The primary outcome was QoL, assessed using EORTC QLQ-C30 and EORTC QLQ-PR25 questionnaires. Secondary outcomes included body composition, fitness, and laboratory parameters. The studies were sourced from PubMed, Embase, and CENTRAL through May 2024. The effect sizes were pooled using random-effects models, and the risk of bias was systematically assessed following the GRADE approach. Results: A total of 30 RCTs, encompassing 2216 PC patients, were analyzed. Combined RT/AT significantly improved QoL subdomains, including global health, and cognitive and sexual function, while reducing fatigue and urinary symptoms. RT alone improved body composition by increasing lean body mass and reducing body fat percentage. Both RT and combined RT/AT enhanced strength (chest and leg press) and VO2peak. No significant changes were observed in laboratory markers, such as PSA or lipid levels. The effects of isolated AT remain unclear due to limited data. Conclusions: RT and combined RT/AT significantly improve QoL, fitness, and body composition in PC patients, with no detectable effect on PSA or lipid levels. Further research is needed to elucidate the specific effects of AT and to investigate long-term outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Lower urinary tract symptoms (LUTS) consist of voiding and storage symptoms. While the therapeutic efficacy of current LUTS medications is limited, and with more than 20% of patients suffering from mixed symptoms, current guidelines offer nothing more than combining monotherapies. An individualized approach is urgently warranted, and phytomedicines have become an integral part of patient-empowerment in therapeutic shared-decision making processes. Therefore, we aimed to investigate patients' preference of phytomedicines and treatment adherence at the dawn of an era leaving α1-blocker monotherapies behind. Patients and Methods: A questionnaire was prepared, and patients at our tertiary referral center were given the opportunity to voluntarily participate in our survey. We collected questionnaires from 300 patients during their visits from January 2022 to December 2022. Results: With 73% (218/300), most of our study cohort had either taken one or more or were currently on prescription medication for LUTS/BPH. Patients were prescribed α1-blockers (72%), followed by 5α-reductase inhibitors (21%), and phosphodiesterase-5-inhibitor (5%), while antimuscarinics and β3-agonists were rarely prescribed. However, 41% (89/218) of our patients, who were taking medication for LUTS, had taken or were currently taking phytomedicines, making this the second most common drug class in our patient cohort. Patients scored the efficacy of phytomedicines at a mean in the lower third, but 87% of patients attributed excellent tolerability, and only 9% experienced side effects. While 43% of patients recommended phytomedicines for other patients, two-thirds of patients thought phytomedicines should be covered by statutory health insurance. Conclusion: We found that phytomedicines were the second most common drug class taken by LUTS patients at our hospital. Reasons may be easy availability as over the counter medication and a superior safety profile with less bothersome side effects than commonly prescribed drug classes. Taken together, phytomedicines may be able to bridge an important gap in LUTS pharmacotherapy to provide sufficient treatment adherence where prescription drug classes fail, and ultimately, adequate improvement of symptoms. However, patients need to be counseled on potentially limited efficacy. [ABSTRACT FROM AUTHOR]

Background: The accurate estimation of residual growth is crucial for the appropriate timing of growth-guiding surgery in patients with axial leg deviations. Skeletal age methods such as the Modified and the Abbreviated Modified Fels Knee System were developed on historical patient cohorts and the applicability to the modern pediatric population with axial leg deviation has not yet been evaluated. Questions/purposes: Are both final adult height prediction methods (the Modified Fels Knee System (FKS) and the Abbreviated Modified Fels Knee System (aFKS)) accurate to determine SA and the final adult height on long leg radiographs in patients with axial leg deviations? Which multiplier table shows highest association between predicted and true final adult body height? Do FKS- and aFKS- skeletal age determination methods improve final adult body height prediction accuracy compared to the simple use of chronological age? Methods: A single center, retrospective study of 31 patients who underwent temporary hemiepiphysiodesis due to axial leg deviations in the frontal plane between 2018 and 2020 was conducted. Skeletal age at the time of surgery was determined on an anterior-posterior long leg X-ray using FKS and aFKS. Adult height predictions were calculated using three different multiplier tables (Paley et al., Sanders-Greulich and Pyle (SGP), Sanders-Peak Height Velocity (PHV)). The accuracy of adult height prediction was determined by comparing the mean differences and mean absolute differences between predicted and true adult height. Results: All adult height predictions overestimated the true adult height. The final height prediction using aFKS and the SGP multiplier showed the lowest overestimation (mean 3.2 cm, SD 5.5 cm). The PHV multiplier table showed the highest correlation between predicted and true adult height (FHPRE_FKS_PHV: r = 0.913, p < 0.001 and FHPRE_aFKS_PHV: r = 0.862, p < 0.001). The simple use of chronological age at the time of surgical intervention (CASI) with the Paley multiplier table showed the highest median delta absolute values and lowest correlations with true adult height (median 7.4 cm, 25%-75% percentile: 3.5–10.0 cm, r = 0.838, p < 0.001). Nevertheless, no significant differences in delta absolute values between various adult height predictions methods could be shown. Conclusions: Overall, the results of the present retrospective cohort study show that there was no significant improvement in final height prediction accuracy when using the FKS or the aFKS method compared to the simple use of chronological age. One reason could be that patients with varus/valgus malalignment have specific growth characteristics that are not accounted for in multiplier tables or the FKS and aFKS method. Since there is no significant difference in prediction accuracy between the methods, the choice of method may depend on other factors, such as clinical preference or availability of resources. However, due to the small sample size, the study cannot definitively rule out potential differences between the prediction methods, and larger studies are required to validate these findings. [ABSTRACT FROM AUTHOR]

Abstract Improved risk stratification of patients suspected of prostate cancer prior to biopsy continues to be an unmet clinical need. ExoDx Prostate (IntelliScore) “EPI” is a non-invasive urine test utilizing RNA from exosomes to provide a risk score that correlates with the likelihood of finding high grade prostate cancer at biopsy. Here, we present the results from a prospective clinical validation study of EPI-CE, a CE-marked in-vitro diagnostic (IVD) assay, specifically developed for use in European clinical laboratories. The study (NCT04720599) enrolled patients with ≥ 50 years, PSA 2–10 ng/mL, prior to MRI, who were scheduled for initial biopsy. First catch urine samples were collected from participants without prior digital rectal examination or prostate massage. Exosomal RNA was isolated and expression levels of three biomarkers ERG, PCA3 and SPDEF were analyzed according to the EPI-CE Instructions For Use. In the study cohort of N = 109 patients, EPI-CE was validated to have a Negative Predictive Value of 89%, a Sensitivity of 92% and a superior performance to two commonly used multiparametric risk calculators (PCPT and ERSPC) in both Receiver Operating Characteristics with a higher Area Under the Curve for EPI-CE 0.67 (95% CI 0.56–0.77) versus PCPT 0.59 (95% CI 0.47–0.71) and ERSPC 0.60 (95% CI 0.49–0.72) and higher Net Benefits analysis across a wide range of risk acceptance levels. This is the first clinical study reporting on the performance of EPI-CE. We demonstrate that EPI-CE provides information beyond standard clinical parameters and provides a better risk assessment prior to MRI, of patients suspected of prostate cancer, than the commonly used multiparametric risk calculators.

Background: NUAKs promote myosin light chain phosphorlyation, actin organization, proliferation and suppression of cell death in non-muscle cells, which are critical for smooth muscle contraction and growth. In benign prostatic hyperplasia (BPH), contraction and growth in the prostate drive urethral obstruction and voiding symptoms. However, a role of NUAKs in smooth muscle contraction or prostate functions are unknown. Here, we examined effects of NUAK silencing and the presumed NUAK inhibitors, HTH01-015 and WZ4003 on contraction and growth-related functions in prostate stromal cells (WPMY-1) and in human prostate tissues.Methods: Effects of NUAK1 and -2 silencing, HTH01-015 and WZ4003 on matrix plug contraction, proliferation (EdU assay, Ki-67 mRNA), apoptosis and cell death (flowcytometry), viability (CCK-8) and actin organization (phalloidin staining) were examined in cultured WPMY-1 cells. Effects of HTH01-015 and WZ4003 on smooth muscle contraction were assessed in organ bath experirments with human prostate tissues.Results: Effects of silencing were most pronounced on proliferation and cell death, resulting in decreases of proliferation rate by 60% and 70% by silencing of NUAK1 and NUAK2 (compared to scramble siRNA-transfected controls), decreases in Ki-67 by 75% and 77%, while numbers of dead cells after silencing of NUAK1 and NUAK2 amounted to 2.8 and 4.9 fold of scramble-transfected controls. Silencing of each isoform was paralleled by reduced viability, breakdown in actin polymerization, and partial decreases in contractility (maximally 45% by NUAK1 silencing, 58% by NUAK2 silencing). Effects of silencing were mimicked by HTH01-015 and WZ4003, with numbers of dead cells amounting up to 16.1 fold or 7.8 fold with HTH01-015 or WZ4003, compared to solvent-treated controls. Using concentrations of 500 nM, neurogenic contractions of prostate tissues were inhibited partly by HTH01-015 and U46619-induced contractions were inhibited partly by HTH01-015 and WZ4003, while α1-adrenergic and endothelin-1-induced contractions remained unaffected. Using 10 μM, inhibition of endothelin-1-induced contractions by both inhibitors and inhibition of α1-adrenergic contractions by HTH01-015 added to effects seen by 500 nM.Conclusion: NUAK1 and -2 suppress cell death and promote proliferation in prostate stromal cells. A role in stromal hyperplasia appears possible in BPH. Effects of NUAK silencing are mimicked by HTH01-015 and WZ4003.

Recently, a novel chipless radio-frequency identification (RFID) concept based on polarimetric radar barcodes was introduced. These tags are similar to the well known optical quick response codes (QR codes). In polarimetric radar barcodes the information is stored as polarimetrically coded areas arranged in a grid and read out by an imaging radar. This paper presents a novel concept for elegantly creating polarimetric barcodes based on dipole scattering domains. Each scattering domain consists of several hundred dipoles. The dipoles are either uniformly arranged at a specific angle, which produces a specific angle-dependent polarization response, or randomly oriented to produce an unpolarized response. In order to read out the polarimetric information stored in the tags, the position and rotation of the radar barcodes needs to be determined. Our research reveals that using three reference elements and a novel decoding algorithm, a position- and rotation-tolerant readout is possible. To reduce distortions caused by the surface of the structure carrying the dipoles, different matching layer concepts were investigated. The novel chipless RFID tag concept is tested using a fully polarimetric W-band (75-$110 \,\mathrm{G}\mathrm{Hz}$) imaging radar. The implemented setup allows for a theoretical data capacity of $1.92 \,\mathrm{bit} \mathrm{/}\mathrm{c}\mathrm{m}^{2}\,$ on a single layer PCB. In our measurements, we achieved a data capacity of $1.52 \,\,\mathrm{bit} \mathrm{/}\mathrm{c}\mathrm{m}^{2}\,$. Utilizing the chosen tag size of $45 \,\mathrm{m}\mathrm{m} \times 45 \,\mathrm{m}\mathrm{m}$ resulted in a tag with a greater than 30 bit data capacity, which is an excellent value for chipless RFID.

ObjectiveThe degree of substitution (DS) of HES describes the average proportion of substituted glucose molecules in a starch molecule. Although no quantitative studies of the in vivo behavior of the DS have been conducted so far, most pharmacokinetic studies to date have measured HES concentrations using the enzymatic method. This method assumes that at any point in time after an infusion, the DS in a serum remains constant and is identical to the DS in the infused solution. In the present study, we examined the changes in the DS of HES 130/0.42 in vivo in an animal model and compared two methods of measuring HES concentrations in plasma (the enzymatic and the o-Toluidine method).MethodologyWe randomized 22 pigs into 2 groups. After induction of anesthesia, the pigs received 500 ml or 1000 ml of HES 130/0.42 (Tetraspan®). The DS was measured directly after the infusion, then after 30, 60, 120 and 240 minutes. In determining the DS, the hydroxyethyl starch was extracted from the plasma and hydrolyzed with hydrochloric acid to form non-substituted glucose and hydroxyethyl glucose. Subsequently, the concentration of free unsubstituted glucose was determined enzymatically and the total concentration of all (i.e., substituted and unsubstituted) glucose molecules was determined using the o-Toluidine method. From this, the concentration of the substituted glucose (hydroxyethyl glucose) and the DS could be calculated. In addition, the HES concentration was measured first in vitro and then in vivo at any point after the infusion by both the enzymatic method and the o-Toluidine method.ResultsThe DS increased significantly directly after the infusion from 0.42 to 0.53 (for 500ml) or to 0.50 (for 1000ml); 4 hours later this had further increased to 0.55 and 0.54, respectively (p ConclusionThe DS of HES in vivo increases significantly over time. As a result, an HES concentration measured with the enzymatic method in vivo will be significantly lower than the same concentration determined with the o-Toluidine method. In future pharmacokinetic studies, HES concentrations should be measured using a method that takes into account changes in the DS in vivo.

Krill represent a major link between primary producers and higher trophic levels in polar marine food webs. Potential links to lower trophic levels, such as heterotrophic microorganisms, are less well documented. Here, we studied the kinetics of microbial degradation of sinking carcasses of two dominant krill species Thysanoessa raschii and Meganyctiphanes norvegica from Southwest Greenland. Degradation experiments under oxic conditions showed that 6.0-9.1% of carbon and 6.4-7.1% of nitrogen were lost from the carcasses after one week. Aerobic microbial respiration and the release of dissolved organic carbon were the main pathways of carbon loss from the carcasses. Ammonium release generally contributed the most to carcass nitrogen loss. Oxygen micro profiling revealed anoxic conditions inside krill carcasses/specimens, allowing anaerobic nitrogen cycling through denitrification and dissimilatory nitrate reduction to ammonium (DNRA). Denitrification rates were up to 5.3 and 127.7 nmol N carcass-1 d-1 for T. raschii and M. norvegica, respectively, making krill carcasses hotspots of nitrogen loss in the oxygenated water column of the fjord. Carcass-associated DNRA rates were up to 4-fold higher than denitrification rates, but the combined activity of these two anaerobic respiration processes did not contribute significantly to carbon loss from the carcasses. Living krill specimens did not harbor any significant denitrification and DNRA activity despite having an anoxic gut as revealed by micro profiling. The investigated krill carcasses sink fast (1500-3000 m d-1) and our data show that only a small fraction of the associated carbon is lost during descent. Based on data on krill distribution, our findings are used to discuss the potential importance of sinking krill carcasses for sustaining benthic food webs in the Arctic.