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Background: Besides second-generation hormone therapy (sHT), upfront docetaxel along with androgen deprivation therapy is the current standard of care for metastasized hormone-sensitive prostate cancer (mHSPC). Evidence on second-line therapy upon progression on chemohormonal treatment outside clinical trials is scarce. Objective: To comparatively assess the efficacy of subsequent therapy after upfront docetaxel in mHSPC in a real-world setting. Design, setting, and participants: This is a retrospective multicenter analysis. Males with mHSPC on androgen-deprivation therapy progressed to castration-resistant prostate cancer (CRPC) after upfront docetaxel. Outcome measurements and statistical analysis: Overall survival (OS), progression-free survival 2 (PFS2), and time to progression 2 (TTP2) were assessed. Chi-square test and Mann-Whitney U test were used for univariate comparison between the sHT and non-sHT (other therapies) cohorts. Median time to event was tested by Kaplan-Meier method and log-rank test. Univariate and multivariate analysis regression was performed with the Cox proportional-hazard model. Results and limitations: Sixty-five patients were included in the final analysis. Median TTP2 was 20 mo, median PFS2 was 29 mo, and median OS was not reached; sHT was an independent predictor of favorable PFS2 as compared with non-sHT. Time to CRPC was also confirmed to be the strongest predictor for novel endpoints PFS2 and TTP2. Time to CRPC >18 mo conferred advantage to sHT over non-sHT in relation to PFS2 and OS. Second-line therapies were well tolerated. The analysis is prone to inherent flaws and biases due to its retrospective nature. Conclusions: In real-world patients progressing after upfront docetaxel, sHT is independently associated with favorable PFS2 favoring drug class switch. Longer time to CRPC predicts strongly for superior PFS2 and TTP2. Further prospective research is warranted in order to guide treatment sequencing and improve outcomes and quality of life of males with metastasized prostate cancer. Patient summary: We analyzed the efficacy of second-line therapy after docetaxel in hormone-dependent metastatic prostate cancer. Novel hormone therapy appears to be a preferable option for deferring progression optimally. Larger patient databases are eagerly awaited. In real-world patients progressing after upfront docetaxel, second-generation hormone therapy is independently associated with superior progression-free survival 2 (PFS2) favoring drug class switch. Longer time to castration-resistant prostate cancer predicts strongly for superior PFS2 and time to progression 2.

The best surgical template for salvage pelvic lymph node dissection (sLND) in patients with nodal recurrence from prostate cancer (PCa) after radical prostatectomy (RP) is currently unknown. We analyzed data of 189 patients with a unilateral positive positron emission tomography (PET) scan of the pelvic lymph node areas, who were treated with bilateral pelvic sLND after RP at 11 high-volume centers. The primary endpoint was missed contralateral disease at final pathology, defined as lymph node positive for PCa in the side opposite to the positive spot(s) at the PET scan. Overall, 93 (49%) and 96 (51%) patients received a 11C-choline and a 68Ga prostate-specific membrane antigen (PSMA) PET scan, respectively, and 171 (90%) and 18 (10%) men had one and two positive spots, respectively. The rate of missed contralateral PCa was 18% (34/189), with the rates being 17% (29/171) and 28% (5/18) in men with one and two positive spots, respectively. While the rate of contralateral disease did not differ between 68Ga-PSMA and 11C-choline (29% and 27%, respectively) among men with two positive spots, the rate of contralateral PCa was only 6% with 68Ga-PSMA versus 28% with 11C-choline in patients with a single positive spot. This finding was confirmed at multivariable logistic regression analysis predicting missed disease at final pathology after accounting for confounders (odds ratio: 0.24; p = 0.001). However, in men with a single positive spot at 68Ga-PSMA PET/computed tomography, the rate of single confirmed lymph node metastasis at final pathology was only 33%, suggesting the need for extended template even if unilateral dissection is performed. Awaiting confirmatory studies, patients diagnosed with a single positive spot at the 68Ga-PSMA PET scan might be considered for unilateral extended pelvic sLND. Patient summary We assessed the risk of missing contralateral disease in patients with a positron emission tomography (PET) scan suggestive of unilateral nodal recurrence from prostate cancer (PCa) after radical prostatectomy and who were treated with bilateral salvage lymph node dissection (sLND). Variability exists according to the number of positive spots and PET tracer, with the lowest rate of missed PCa in men diagnosed with a single positive spot at a 68Ga prostate-specific membrane antigen PET scan (6%). If replicated, our data suggest that these patients might be considered for unilateral extended pelvic sLND.

Background: The optimal definition and prognostic significance of persistently elevated prostate-specific antigen (PSA) after salvage lymph node dissection (sLND) for node-only recurrent prostate cancer (PCa) remain unknown. Objective: To assess the definition and clinical implications of persistently elevated PSA after sLND for node-only recurrent PCa after radical prostatectomy. Design, setting, and participants: The study included 579 patients treated with sLND at 11 high-volume centers between 2000 and 2016. Outcome measurements and statistical analysis: We assessed the linear relationship between the first PSA after sLND and death from PCa. Different definitions of PSA persistence were included in a multivariable model predicting cancer-specific mortality (CSM) after surgery to identify the best cutoff value. We investigated the association between PSA persistence and oncologic outcomes using multivariable regression models. Moreover, the effect of early androgen deprivation therapy (ADT) after sLND was tested according to PSA persistence status and estimated risk of CSM. Results and limitations: We found an inverse relationship between the first PSA after sLND and the probability of cancer-specific survival. PSA persistence defined as first postoperative PSA ≥0.3 ng/ml provided the best discrimination accuracy (C index 0.757). According to this cutoff, 331 patients (57%) experienced PSA persistence. The median follow-up for survivors was 48 mo (interquartile range 27-74). After adjusting for confounders, men with persistently elevated PSA had higher risk of clinical recurrence (hazard ratio [HR] 1.61), overall mortality (HR 2.20), and CSM (HR 2.59; all p 10%. Conclusions: PSA persistence after sLND independently predicts adverse prognosis, with the best discrimination accuracy for CSM provided by a definition of PSA ≥ 0.3 ng/ml. We showed that when stratifying patients by final pathology results and PSA persistence status, early ADT use after sLND was beneficial only for patients with PSA persistence or with a calculated 5-yr risk of CSM of >10%, which could be useful as we await results from ongoing prospective trials. Patient summary: We found that for patients with prostate cancer who had lymph nodes removed after their cancer recurred, persistently elevated prostate-specific antigen (PSA) levels predict poorer prognosis. We showed that a PSA level of ≥0.3 ng/ml provides the best accuracy in identifying patients with worse prognosis. This may help to improve risk stratification after lymph node removal and allow physicians to optimize treatment strategies after surgery.

Digital firms tend to be both narrow in their vertical scope and large in their scale. We explain this phenomenon through a theory about how attributes of firms' resource bundles impact their scale and specialization. We posit that highly scalable resource bundles entail significant opportunity costs of integration (versus outsourcing), which simultaneously drive "hyperspecialization" and "hyperscaling" in digital firms. Using descriptive theory and a formal model, we develop several propositions that align with observed features of digital businesses. We offer a parsimonious modeling framework for resource-based theorizing about highly scalable digital firms, shed light on the phenomenon of digital scaling, and provide insights into the far-reaching ways that technology-enabled resources are reshaping firms in the digital economy.

Purpose of review To investigate the features and optimal management of pN+ cM0 prostate cancer (PCa) according to registry-based studies. Recent findings Up to 15% of PCa patients harbor lymph node invasion (pN+) at radical prostatectomy plus lymph node dissection. Nonetheless, the optimal management strategy in this setting is not well characterized. Summary We performed a systematic review including n = 13 studies. Management strategies comprised 13 536 men undergoing observation, 11 149 adjuvant androgen deprivation therapy (aADT), 7,075 adjuvant radiotherapy (aRT) +aADT and 705 aRT. Baseline features showed aggressive PCa in the majority of men. At a median follow-up ranging 48-134months, Cancer-related death was 5% and overall-mortality 16.6%. aADT and aRT alone had no cancer-specific survival or overall survival advantages over observation only and over not performing aRT, respectively. aADT plus aRT yielded a survival benefit compared to observation and aADT, which in one study, were limited to certain intermediate-risk categories. Age, Gleason, Charlson score, positive surgical margins, pathological stage, and positive nodes number, but not prostate specific antigen, were most relevant prognostic factors. Our work further confirmed pN+ PCa is a multifaceted disease and will help future research in defining its optimal management based on different risk categories to maximize survival and patient's quality of life.

Twin studies suggest a substantial role for genes in explaining individual differences in aggressive behavior across development. It is unclear, however, how directly measured genetic risk is associated with aggressive behavior at different moments across adolescence and how genes might distinguish developmental trajectories of aggressive behavior. Here, a polygenic risk score derived from the EAGLE-Consortium genome-wide association study of aggressive behavior in children was tested as predictor of latent growth classes derived from those measures in an adolescent population (n = 2229, of which n = 1246 with genetic information) and a high-risk sample (n = 543, of which n = 335 with genetic information). In the population sample, the polygenic risk score explained variation in parent-reported aggressive behavior at all ages and distinguished between stable low aggressive behavior and moderate and high-decreasing trajectories based on parent-report. In contrast, the polygenic risk score was not associated with self- and teacher-reported aggressive behavior, and no associations were found in the high-risk sample. This pattern of results suggests that methodological choices made in genome-wide association studies impact the predictive strength of polygenic risk scores, not just with respect to power but likely also in terms of generalizability and specificity.

Effective obesity prevention requires intervening at all levels of society, including the governmental level. Policy interventions at the governmental level are especially promising as they tend to involve minimal individual effort while, at the same time, reach many people. The amount of state-level obesity-related legislation in the United States has increased over the years, and several laws were installed in contexts that reach young people, such as schools. Given this increase in state-level obesity-related legislation targeting youth, we tested whether the quantity of obesity-related legislation in U.S. states was associated with adolescent BMI and overweight/obesity prevalence. Linear and multilevel analyses showed that the quantity of physical activity-related legislation was associated with lower overweight/obesity prevalence yet with very modest effect size (b = -0.002, p = .042). Our results underline the likely importance of obesity-related legislation. In addition, the value of examining both BMI and overweight/obesity prevalence when evaluating interventions is demonstrated.

Lukas Rath, Friedrich Jokisch, Gerald Bastian Schulz, Alexander Kretschmer, Alexander Buchner, Christian G Stief, Philipp Weinhold Department of Urology, Ludwig-Maximilians-University, Munich, GermanyCorrespondence: Philipp WeinholdDepartment of Urology, Ludwig-Maximilians-University, Marchioninistrasse 15, Munich, 81377, GermanyTel +4989-4400-73528Fax +49894400-78735Email philipp.weinhold@med.uni-muenchen.dePurpose: There are only a few case reports and case series that investigated combined laparoscopic or robotic surgery for simultaneous prostate and kidney cancer. In this study, we want to close a gap in existing research to assess the feasibility and oncological outcome of combined open prostatectomy and kidney surgery.Methods: We retrospectively analyzed patients who underwent a combined open prostatectomy and either a partial or complete nephrectomy from 2013 to 2020. Descriptive statistics were used to assess perioperative parameters and the 12-month functional and oncological outcomes after combined surgery.Results: We identified 10 patients undergoing combined open surgery. Partial nephrectomy was performed in 4, radical nephrectomy in 6 patients. For prostate cancer, histopathological analysis showed a tumor stage ≥ pT2c in all 10 patients. For renal tumors, histopathological analysis showed clear cell renal cell carcinoma in 8 patients and oncocytoma in 2 patients. Operating time was 177 ± 36 minutes. Two perioperative complications (Clavien 2a and 3) were observed. Three months postoperatively, the International Index of Erectile Function (IIEF-5) score was 5.6 ± 5.9, the ICIQ-SF score was 7.3 ± 5.6 and were using 1.9 ± 2.2 pads per day. This improved after 12 months postoperatively, as patients had an IIEF-5 score of 6.33 ± 6.5, an ICIQ-SF score of 4.4 ± 5.7 and were using pads 0.9 ± 1.7 per day.Conclusion: In this study, we showed that open surgery is a safe and valid approach for combined prostatectomy and renal surgery with acceptable complications and oncological outcomes. The combined open approach could be a good alternative to combined laparoscopic/robotic surgery in this field, especially to treat patients with advanced renal tumors or previous abdominal surgery or radiation.Keywords: retropubic prostatectomy, kidney surgery, simultaneous prostate and kidney cancer, combined surgery

Purpose Nodal recurrent prostate cancer (PCa) represents a common state of disease, amenable to local therapy. PSMA-PET/CT detects PCa recurrence at low PSA levels. The aim of this study was to evaluate the outcome of PSMA-PET/CT-based salvage radiotherapy (sRT) for lymph node (LN) recurrence. Methods A total of 100 consecutive patients treated with PSMA-PET/CT-based salvage elective nodal radiotherapy (sENRT) for LN recurrence were retrospectively examined. Patients underwent PSMA-PET/CT scan due to biochemical persistence (bcP, 76%) or biochemical recurrence (bcR, 24%) after radical prostatectomy (RP). Biochemical recurrence-free survival (BRFS) defined as PSA Results Median follow-up was 37 months. Median PSA at PSMA-PET/CT was 1.7 ng/ml (range 0.1–40.1) in patients with bcP and 1.4 ng/ml (range 0.3–5.1) in patients with bcR. PSMA-PET/CT detected 1, 2, and 3 or more LN metastases in 35%, 23%, and 42%, respectively. Eighty-three percent had only pelvic, 2% had only paraaortic, and 15% had pelvic and paraaortic LN metastases. Cumulatively, a total dose converted to EQD21.5 Gy of 66 Gy (60–70 Gy) was delivered to the prostatic fossa, 70 Gy (66–72 Gy) to the local recurrence, if present, 65.1 Gy (56–66 Gy) to PET-positive lymph nodes, and 47.5 Gy (42.4–50.9 Gy) to the lymphatic pathways. Concomitant androgen deprivation therapy (ADT) was administered in 83% of patients. One-, 2-, and 3-year BRFS was 80.7%, 71.6%, and 65.8%, respectively. One-, 2-, and 3-year DMFS was 91.6%, 79.1%, and 66.4%, respectively. In multivariate analysis, concomitant ADT, longer ADT duration (≥ 12 vs. 1 ng/ml) with improved DMFS, respectively. No such association was seen for the number of affected lymph nodes. Conclusions Overall, the present analysis shows that the so far, unmatched sensitivity and specificity of PSMA-PET/CT translates in comparably high BRFS and DMFS after PSMA-PET/CT-based sENRT for patients with PCa LN recurrence. Concomitant ADT, duration of ADT, PSA value before sRT, and localization of LN metastases were significant factors for improved outcome.

Der „Athertag“, ein Schlusselmoment in der Geschichte der Menschheit, jahrt sich am 16. Oktober 2021 zum 175. Mal. Nachdem der Zahnarzt William T. G. Morton in Boston die erste erfolgreiche offentliche Athernarkose gegeben hatte, schien es von nun an moglich, Menschen mit vertretbarem Risiko vor Schmerz zu bewahren und gleichzeitig durch die Induktion von Bewusstlosigkeit vor psychischen Folgeschaden zu schutzen. Der Philosoph Peter Sloterdijk spricht von einem „Recht auf Nicht-Dabei-Sein-Mussen“, das die Anasthesie dem Menschen seit 1846 ermoglicht, und leitet daraus „gewissermasen ein Menschenrecht auf Ohnmacht“ ab. Die Umsetzung dieser Idee liegt jedoch in weiter Ferne. Zum einen fehlt in vielen Landern in groser Zahl qualifiziertes Personal, um selbst Narkosen fur lebensnotwendige Operationen durchfuhren zu konnen. Zum anderen ist uber Jahrzehnte klar geworden, dass die Anasthesie fur die Menschheit nicht nur segensreich ist, sondern auch ihre „dunkle Seite“ zeigen kann: Substanzmissbrauch, Einsatz von Anasthetika bei Folterungen und Hinrichtungen. Zudem ist der Stellenwert der Anasthetika bei Wiederbelebungsmasnahmen, in der Palliativmedizin und zur Erleichterung von Hinrichtungen unklar oder umstritten. Letztlich sind auch die erforderlichen formlichen Schritte zur (volker)rechtlichen Anerkennung eines „Menschenrechts auf Ohnmacht“ bislang nicht vollzogen worden.

Introduction The COVID-19 outbreak has become the dominant issue throughout the world whilst the governments, nations and health services are trying to deal with its impact. The aim of our study is to assess the impact of COVID-19 on patients treated with radical prostatectomy (RP) for prostate cancer (PCa) at European referral centers in terms of surgical volume (SV), waiting list meant as time from biopsy to surgery (WL) and risk of adverse pathologic findings at RP due to the selection of men with more adverse disease characteristics at final pathology. Material and methods Consecutive patients with a diagnosis of histologically proven PCa treated with RP between March 2020 (WHO declaration of pandemic) and December 2020 were identified. Patients with metastatic disease not eligible to local treatment and recurrent prostate cancer after RP or RT were excluded. Patients treated at the same institutions between March 2019 and December 2019 were considered as the control group. Multivariable logistic regression analysis tested the impact of the COVID-19 outbreak on the risk of adverse pathologic findings at RP after adjusting for confounders. The percentage change of SV and WL was assessed comparing the months of pandemic with the equivalent timespan of the previous year. Results A total of 2,574 patients treated with RP (927 cases and 1647 controls) were identified in 8 European tertiary referral centers. At multivariable analysis patients who were treated during the pandemic had higher risk of extra prostatic disease (OR:1.35, p = 0.038) and lymph node invasion (LNI) (OR:1.72, p = 0.048). An average 23% reduction of the SV with the equivalent timespan of the previous year allowed an illusory reduction of the WL after the peak gained during the first wave of COVID-19. Conclusions Our results showed that the COVID-19 outbreak resulted in a delay in the administration of curative-intent therapies in patients with localized PCa. This, in turn, resulted in a stage migration phenomenon with a potential impact on oncologic control. Weitere Verfasser:innen aus Einrichtungen außerhalb der Universität Duisburg-Essen sind nicht aufgeführt.

PurposeOver recent years, public relations (PR) research has diversified in themes and theories. As a result, PR presents itself today as a multi-paradigmatic discipline with competing ideas of progress that mainly circle around questions of ontology and epistemology, i.e. around defining appropriate object and knowledge in PR research.Design/methodology/approachThis conceptual article highlights a third crucial question underlying the debate drawing on a narrative approach: The question of axiology, hence, the normative question how PR research shall develop to contribute to societal progress.FindingsThe article presents a model, which describes how normative visions of progress in different PR paradigms – functional, co-creational, social-reflective and critical-cultural – manifest in each distinct combinations of four narrative plots – tragedy, romance, comedy and satire.Originality/valueThese findings complement the current debate on disciplinary progress in PR research by fostering reflection and debate on paradigm development and cross-paradigmatic tensions and exchange from an explicit axiological perspective.

OBJECTIVE: To determine if thoracic spine manipulation (TSM) improves pain and disability in individuals with cervicogenic headache (CeH). METHODS: A randomized controlled crossover trial was conducted on 48 participants (mean age: 34.4 years) with CeH symptoms. Participants were randomized to 6 sessions of TSM or no treatment (Hold) and after 4-weeks, groups crossed over. Outcomes were collected at 4, 8 and 12 weeks and included: headache disability inventory (HDI), neck disability index (NDI), and the global rating of change (GRC). Outcomes were analyzed using a linear mixed-effects model with Bonferroni correction. Odds of achieving the minimal clinically important difference (MCID) on the GRC of +4 or greater were also calculated. Scores at 4 weeks represent the only timepoint where 1 group is fully treated and other group has not received any treatment. RESULTS: Comparing hold to active treatment, HDI were not significantly different between groups (mean difference = 7.39, 95 CI: −4.39 to 19.18; P = 0.214) at any timepoint; the NDI was significant (mean difference = 6.90, 95 CI: 0.05 to 13.75; P = 0.048) at 4 weeks. Odds of achieving the +4 MCID on the GRC (OR = 38.0, 95 CI: 6.6 to 220.0; p

The General Data Protection Regulation (GDPR) is in effect since May of 2018. As one of the most comprehensive pieces of legislation concerning privacy, it sparked a lot of discussion on the effect it would have on users and providers of online services in particular, due to the large amount of personal data processed in this context. Almost three years later, we are interested in revisiting this question to summarize the impact this new regulation has had on actors in the World Wide Web. Using Scopus, we obtain a vast corpus of academic work to survey studies related to changes on websites since and around the time the GDPR went into force. Our findings show that the emphasis on privacy increased w.r.t. online services, but plenty potential for improvements remains. Although online services are on average more transparent regarding data processing practices in their public data policies, a majority of these policies still either lack information required by the GDPR (e.g., contact information for users to file privacy inquiries) or do not provide this information in a user-friendly form. Additionally, we summarize that online services more often provide means for their users to opt out of data processing, but regularly obstruct convenient access to such means through unnecessarily complex and sometimes illegitimate interface design. Our survey further details that this situation contradicts the preferences expressed by users both verbally and through their actions, and researchers have proposed multiple approaches to facilitate GDPR-conform data processing without negatively impacting the user experience. Thus, we compiled reoccurring points of criticism by privacy researchers and data protection authorities into a list of four guidelines for service providers to consider.

Existing end-to-end-encrypted (E2EE) email systems, mainly PGP, have long been evaluated in controlled lab settings. While these studies have exposed usability obstacles for the average user and offer design improvements, there exist users with an immediate need for private communication, who must cope with existing software and its limitations. We seek to understand whether individuals motivated by concrete privacy threats, such as those vulnerable to state surveillance, can overcome usability issues to adopt complex E2EE tools for long-term use. We surveyed regional activists, as surveillance of social movements is well-documented. Our study group includes individuals from 9 social movement groups in the US who had elected to participate in a workshop on using Thunderbird+Enigmail for email encryption. These workshops tool place prior to mid-2017, via a partnership with a non-profit which supports social movement groups. Six to 40 months after their PGP email encryption training, more than half of the study participants were continuing to use PGP email encryption despite intervening widespread deployment of simple E2EE messaging apps such as Signal. We study the interplay of usability with social factors such as motivation and the risks that individuals undertake through their activism. We find that while usability is an important factor, it is not enough to explain long term use. For example, we find that riskiness of one's activism is negatively correlated with long-term PGP use. This study represents the first long-term study, and the first in-the-wild study, of PGP email encryption adoption., Comment: To be published in: Proceedings of the 21st Privacy Enhancing Technology Symposium (PoPETS), Issue 3

Sentinel lymph node (SN) tumor burden is becoming increasingly important and is likely to be included in future N classifications in melanoma. Our aim was to investigate the prognostic significance of melanoma infiltration of various anatomically defined lymph node substructures. This retrospective cohort study included 1250 consecutive patients with SN biopsy. The pathology protocol required description of metastatic infiltration of each of the following lymph node substructures: intracapsular lymph vessels, subcapsular and transverse sinuses, cortex, paracortex, medulla, and capsule. Within the SN with the highest tumor burden, the SN invasion level (SNIL) was defined as follows: SNIL 1 = melanoma cells confined to intracapsular lymph vessels, subcapsular or transverse sinuses; SNIL 2 = melanoma infiltrating the cortex or paracortex; SNIL 3 = melanoma infiltrating the medulla or capsule. We classified 338 SN-positive patients according to the non-metric SNIL. Using Kaplan–Meier estimates and Cox models, recurrence-free survival (RFS), melanoma-specific survival (MSS) and nodal basin recurrence rates were analyzed. The median follow-up time was 75 months. The SNIL divided the SN-positive population into three groups with significantly different RFS, MSS, and nodal basin recurrence probabilities. The MSS of patients with SNIL 1 was virtually identical to that of SN-negative patients, whereas outgrowth of the metastasis from the parenchyma into the fibrous capsule or the medulla of the lymph node indicated a very poor prognosis. Thus, the SNIL may help to better assess the benefit-risk ratio of adjuvant therapies in patients with different SN metastasis patterns.

Aims Radical cystectomy and urinary diversion impact various dimensions of patients' health-related-quality-of-life (HRQOL). Yet, less is known about salvage cystectomy as a last-line option for treatment-refractory benign diseases. Therefore, our aim is to provide HRQOL data from a contemporary cohort of open salvage cystectomies for benign conditions. Methods Fifty-four consecutive patients were enrolled in one single tertiary referral center. Analysis was limited to patients undergoing urinary diversion via ileal conduit (IC). Complications were assessed via Clavien-Dindo-scale. HRQOL was measured using the validated European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-BLM30 questionnaire. HRQOL QLQ-C30 domains were measured preoperatively and up to 3 years postoperatively. Longitudinal changes were analyzed using Friedman's rank test. Primary endpoint was good general HRQOL based on QLQ-C30 global health status (GHS). Multivariate analysis was performed using logistic regression models with a step-wise backward selection procedure. Results Longitudinal analysis of HRQOL subdomains revealed significantly improved pain (p = .005) and fatigue (p = .002) scores as well as improved social functioning (p = .038). Furthermore, general HRQOL (GHS scores) improved significantly during the follow-up period (28.0 vs. 50.6 [36 months], p = .045). In multivariate analysis, the indication for salvage cystectomy could not be identified as an independent predictor for good general HRQOL. We observed a total number of 10 (41.7%) high-grade (Clavien ≥III) 90 day-complications. Limitations include limited follow-up rates at respective time-points. Conclusion Salvage cystectomy and IC can be safely performed as a last-line treatment for benign conditions and increases general HRQOL in the long-term follow-up. Thus, it can play a role in a holistic approach for a challenging clinical setting.

Zusammenfassung Ziel der Studie Die Häufigkeit Seltener Erkrankungen im Krankengut von Krankenhäusern und Universitätsklinika ist unbekannt. Der ICD-10 bildet Diagnosen Seltener Erkrankungen nur unzureichend ab, über entsprechende Entlassdiagnosen ist die Häufigkeit Seltener Erkrankungen nicht abschätzbar. Die Systematik des gegenwärtigen Krankenhausentgeltsystems scheint nicht auf eine leistungsgerechte Vergütung in der Behandlung dieser Erkrankungen ausgelegt. Durch Einführung einer verpflichtenden Dokumentation von Seltenen Erkrankungen sollte erstmalig eine repräsentative Abschätzung der Häufigkeit von stationär behandelten Seltenen Erkrankungen an einem Universitätsklinikum gegeben werden. Methodik Seit 2017 erfolgt für alle stationär behandelten Patienten des Universitätsklinikums Dresden die obligate Abfrage, ob eine Seltene Erkrankung vorliegt. Im Falle eines Vorliegens, erfolgt eine Kodierung der Seltenen Erkrankung auf Basis der Orpha-Kennnummer, welche dazu in das Krankhausinformationssystem ORBIS implementiert wurde. Ergebnisse Exemplarisch wurde das Jahr 2019 ausgewertet, in welchem am Universitätsklinikum Dresden von insgesamt 70 937 Entlassfällen für 19% eine Seltene Erkrankung kodiert wurde. Schlussfolgerung Erstmals wurde eine prospektive und als lückenlos anzusehende Erhebung von Seltenen Erkrankungen an einem deutschen Universitätsklinikum umgesetzt. Die seitens der Europäischen Union definierte Prävalenz Seltener Erkrankungen von 6 bis 8% wurde um ein Mehrfaches überschritten. Mit hoher Wahrscheinlichkeit wird die tatsächliche Häufigkeit dennoch erheblich unterschätzt, da die Qualität der Kodierung mit der Nutzercompliance korreliert. Dadurch unterstreicht die Erfassung die besondere Rolle von Patienten mit Seltener Erkrankung in der Versorgungsrealität von Universitätsklinika.

Objective The Care of Late-Stage Parkinsonism (CLaSP) study aimed to collect qualitative and standardized patient data in six European countries (France, Germany, Netherlands, Portugal, UK, Sweden) to enable a detailed evaluation of the underexplored late stages of the disease (Hoehn and Yahr stage > 3) using clinical, neuropsychological, behavioral, and health economic data. The aim of this substudy was to provide a health economic evaluation for the German healthcare system. Methods In Germany, 228 patients were included in the study. Costs were calculated from a societal perspective for a 3-month period. Univariate analyses were performed to identify cost-driving predictors. Total and direct costs were analyzed using a generalized linear model with a γ-distributed dependent variable and log link function. Indirect costs were analyzed using a binomial generalized linear model with probit link function. Results The mean costs for the 3-month period were approximately €20,000. Informal care costs and hospitalization are approximately €11,000 and €5000. Direct costs amounted to 89% of the total costs, and the share of indirect costs was 11%. Independent predictors of total costs were the duration of the disease and age. The duration of the disease was the main independent predictor of direct costs, whereas age was an independent predictor of indirect costs. Discussion Costs in the late stage of the disease are considerably higher than those found in earlier stages. Compared to the latter, the mean number of days in hospital and the need for care is increasing. Informal caregivers provide most of the care. Clinical Trial Registration The protocol was registered at ClinicalTrials.gov as NCT02333175 on 7 January, 2015. Supplementary Information The online version contains supplementary material available at 10.1007/s40273-021-01011-y.

Die Exposition gegenuber Umweltgiften ist ubiquitar in industrialisierten Landern. Expositionsrouten und gesundheitsrelevante Effekte besonders mit Blick auf die Reproduktion bei Frauen und der intrauterinen Entwicklung von Kindern sowie perinatale Programmierung. Auswertung und Reflektion aktueller Publikationen zum Thema mit Darstellung neuster Erkenntnisse und relevanter Zukunftsperspektiven. Durch epidemiologische Studien gilt als gesichert, dass Menschen und Tiere heute einer Vielzahl von Umweltgiften ausgesetzt sind und trotz strenger Grenzwerte gesundheitsrelevante Effekte nicht ausgeschlossen werden konnen, sondern als sehr wahrscheinlich gelten. Mechanistische Untersuchungen tragen zum besseren Verstandnis und zur Verdeutlichung der Dringlichkeit bei. Mit weiterfuhrenden epidemiologischen und experimentellen Studien konnen Bedeutung und Risiken fur die Reproduktion und die kindliche Entwicklung durch Umweltgifte besser ergrundet und politische Entscheidungsfindung sowie medizinische Pravention von Gesundheitseffekten vorangetrieben werden.

Aim of the study Next-generation sequencing (NGS) might represent a valuable diagnostic tool to identify somatic alterations and enable personalised medicine in uro-oncology. We aim to determine feasibility and impact of routine NGS in clinical practice. Methods Tumours from patients with genitourinary cancers were subjected to NGS. Results were discussed in a dedicated molecular tumour board. Statistical analyses included chi-square test and Mann-Whitney U test. Results Between 2017 and 2020, 65 patients with advanced genitourinary cancers were consecutively enrolled. Number of tests increased (28 tests in 2020) and diagnostic turnaround time for generating output decreased (17.5 days [range 13–35]). Median patient's age was 62 years (range 33–84), and most NGS assays were performed upon start of systemic treatment (range 0–6 of treatment lines). 62/66 sequenced samples generated a report. Fifty samples (80.6%) showed at least one molecular alteration. Most prevalent alterations were TP53 (32.3%), PIK3CA (14.5%) and TMPRSS2-ERG (9.7%). Sequencing revealed potentially druggable targets in 29 samples (46.8%). Based on NGS results, six patients underwent therapy change, whereas for three patients, coverage of recommended off-label therapy was denied by health insurances. Conclusions NGS is increasingly feasible in clinical routine for patients with genitourinary cancers. Number of performed analyses is constantly growing, and turnaround time to therapy recommendation is decreasing. While the majority of tumours harbour clinically relevant mutations, alterations related to urologic cancers are underrepresented, thus treatment changes occurred only in a minority of patients. Further, access to target agents remains a considerable obstacle in the consequent implementation of precision uro-oncology.

Objective To evaluate hip fracture patients´ views on content validity and feasibility of four commonly used generic measures of health-related quality of life (HRQOL). Methods We interviewed 32 elderly hip fracture patients without relevant cognitive impairment (mean age=81 years). Using think-aloud and verbal probing techniques, patients completed the EQ-5D descriptive system, Nottingham Health Profile (NHP), Short-Form 12 Health Questionnaire (SF-12) and WHO Quality of Life-BREF (WHOQOL-BREF). Results Patients were mostly not able to self-complete the questionnaires. Content validity was most constrained by problems in comprehensibility (e.g. vaguely phrased). Some items, for instance, were considered irrelevant if the example was inappropriate. Patients named e.g. problems with vision as important for their HRQOL, but none of the instruments included related items. Conclusion Although patients reported problems with all instruments, we suggest the EQ-5D or SF-12, as these appear to have the fewest limitations in content validity and feasibility from the patient´s perspective.

Objective: The aim of this study was to assess the security, value, and efficacy of the second-generation AdVance male sling XP (Boston Scientific®), after implementation in 2010 with advantageous modifications in the sling structure and needle shape, in a prospective multicenter long-term follow-up study. Methods: In total, 115 patients were included. Exclusion criteria were earlier incontinence (UI) surgery, nocturnal UI, former radiotherapy, or night-time incontinence. We also excluded patients with a functional urethra Results: The 24-month follow-up (114 patients) revealed 64.0% cured and 28.8% improved patients. Mean urine loss was reduced significantly to 19.0 g (p < 0.001). A mean PGI score of 1.5 and a mean VAS score of 0.2 were obtained. The 60-month follow-up (59 patients) revealed 57.6% cured and 25.4% improved patients. Mean urine loss was reduced significantly to 18.3 g (p < 0.001). A mean PGI score of 1.6 and a mean VAS score of 0.2 were obtained. Conclusions: The AdVance XP displays excellent continence results and secure effectiveness over a 5-year period. Moreover, these data are demonstrating low complication rates and improved quality of life in the long-term use of AdVance XP.

We aimed to evaluate the efficacy and safety of a low-dose imaging protocol to reduce intraprocedural radiation during transcatheter aortic valve implantation (TAVI). Observational analysis: 802 transfemoral TAVI patients receiving balloon-expandable devices ≥23 mm at a high-volume centre. After propensity score matching, a standard-dose group (SD, n = 333) treated between January 2014 and February 2016 was compared with a low-dose group (LD, n = 333) treated between August 2017 and March 2019 after departmental uptake of a low-dose imaging protocol (reduced field size, high table height, use of “fluoro save,” 3.75 frames/second acquisition, increased filtering). Primary end point was dose-area product (DAP). Secondary safety end points were VARC-2 device success and a composite of in-hospital complications. The LD protocol was associated with lower DAP (4.64 [2.93, 8.42] vs 22.73 [12.31, 34.58] Gy⋅cm2, p

The role and timing of radiotherapy (RT) in prostate cancer (PCa) patients treated with radical prostatectomy (RP) remains controversial. While recent trials support the oncological safety of early salvage RT (SRT) compared to adjuvant RT (ART) in selected patients, previous randomized studies demonstrated that ART might improve recurrence-free survival in patients at high risk for local recurrence based on adverse pathology. Although ART might improve survival, this approach is characterized by a risk of overtreatment in up to 40% of cases. SRT is defined as the administration of RT to the prostatic bed and to the surrounding tissues in the patient with PSA recurrence after surgery but no evidence of distant metastatic disease. The delivery of salvage therapies exclusively in men who experience biochemical recurrence (BCR) has the potential advantage of reducing the risk of side effects without theoretically compromising outcomes. However, how to select patients at risk of progression who are more likely to benefit from a more aggressive treatment after RP, the exact timing of RT after RP, and the use of hormone therapy and its duration at the time of RT are still open issues. Moreover, what the role of novel imaging techniques and genomic classifiers are in identifying the most optimal post-operative management of PCa patients treated with RP is yet to be clarified. This narrative review summarizes most relevant published data to guide a multidisciplinary team in selecting appropriate candidates for post-prostatectomy radiation therapy.

Focal therapy is a modern alternative to selectively treat a specific part of the prostate harboring clinically significant disease while preserving the rest of the gland. The aim of this therapeutic approach is to retain the oncological benefit of active treatment and to minimize the side-effects of common radical treatments. The oncological effectiveness of focal therapy is yet to be proven in long-term robust trials. In contrast, the toxicity profile is well-established in randomized controlled trials and multiple robust prospective cohort studies. This narrative review summarizes the relevant evidence on complications and their management after focal therapy. When compared to whole gland treatments, focal therapy provides a substantial benefit in terms of adverse events reduction and preservation of genito-urinary function. The most common complications occur in the peri-operative period. Urinary tract infection and acute urinary retention can occur in up to 17% of patients, while dysuria and haematuria are more common. Urinary incontinence following focal therapy is very rare (0–5%), and the vast majority of patients recover in few weeks. Erectile dysfunction can occur after focal therapy in 0–46%: the baseline function and the ablation template are the most important factors predicting post-operative erectile dysfunction. Focal therapy in the salvage setting after external beam radiotherapy has a significantly higher rate of complications. Up to one man in 10 will present a severe complication.

Recently, adoption of novel drugs for systemic treatment of metastatic prostate cancer has led to a striking improvement of response rate and survival in both hormone-sensitive and castration-resistant disease. In most cases, prostate cancer essentially depends on androgen receptor signaling axis, even in castration-resistant setting, and hence may be targeted by second generation hormonal therapy. However, a subset of patients bears androgen-independent cancer biology with a short-term response to hormonal treatment, early and extensive visceral metastases, low PSA levels and poor outcomes. Identification and specific management of these rapidly fatal malignancies is of an unmet medical need since their classification and utilized therapeutic regimens vary significantly. Unfortunately, molecular pathways have not been sufficiently elucidated yet in order to provide an effective targeted treatment with a prolonged response. Lack of diagnostic and predictive biomarkers for these cancers makes successful counteractions against them even more sophisticated. In this comprehensive review, we aimed at summarizing the current body of literature reporting on causal molecular machinery as well as diagnostic and therapeutic concepts of aggressive prostate tumors and draw clinically relevant conclusions for the up-to-date sensible disease management.

In recent years there have been substantial changes in the therapeutic landscape for systemic treatment of advanced prostate cancer (PCa), which resulted in a multitude of novel treatment options for different stages of the disease. In the current narrative review currently available treatment options for metastatic hormone-sensitive PCa as well as nonmetastatic castration-resistant PCa are presented. In addition, current treatment sequence options and targeted treatment in the stage of metastatic castration-resistant PCa are highlighted.

Platform ecosystems have spurred new products and services, sparked innovation, and improved economic efficiency in various industries and technology sectors. A distinctive feature of the platform architecture is its modular and interdependent system of core and complementary components bound together by design rules and an overarching value proposition. Accordingly, we conceptualize platforms as meta-organizations, or “organizations of organizations” that are less formal and less hierarchical structures than firms, and yet more closely coupled than traditional markets. To function successfully, however, platforms require coordination among multiple participants not all of whose interests are aligned. These organizational features of platforms raise many interesting and complex strategic challenges and hold implications for how platforms compete. In this paper, we discuss some of the most salient features of platform ecosystems as meta-organizations, specifically in terms of the sources of authority or power in the ecosystem, the motivation and incentives a platform creates to attract participants, and its governance and coordination structures. We then consider how papers appearing in this special issue inform us about the effects of these features on platform competition along three distinct dimensions: (a) with traditional incumbents as platforms enter and establish themselves in new markets, (b) with other platforms to secure an advantageous market position, and (c) with the different participants on the platform to share the value that has been created jointly. We close by identifying some promising directions for future research. Managerial summary Platform ecosystems have spurred new products and services, sparked innovation, and improved economic efficiency in various industries and technology sectors. A distinctive feature of the platform architecture is its modular and interdependent system of core and complementary components bound together by design rules and an overarching value proposition. This makes platform ecosystems an organizational form on its own (a “meta-organization”), neither possessing the hierarchical instruments of a firm, nor the largely uncoordinated decisionmaking of markets. Successful platform ecosystems require coordination among multiple participants with possibly conflicting interests. We discuss some of the most salient features of platform ecosystems as meta-organizations, specifically in terms of the sources of authority or power in the ecosystem, the motivation and incentives a platform creates to attract participants, and its governance and coordination structures. These features affect how platform ecosystems compete: i) with a traditional incumbent, ii) with other platform ecosystems, and iii) between different participants of the same platform ecosystem. The articles published in this special issue speak to different aspects of platform competition from the perspective of organization design.

[Purpose] Examination and treatment of the long head of the biceps tendon (LHBT) requires accurate palpation. The purpose of this study was to determine physical therapists' reliability and ability to accurately palpate the LHBT in two arm positions with ultrasound as the gold standard. [Participants and Methods] Examiners palpated the LHBT within the intertubercular groove (ITG) of the humerus on the bilateral shoulders of 32 asymptomatic (21 female; 24.3 ± 1.9 years) participants in 2 arm positions. The magnitude of distance between a marker and the border of the ITG was compared between 2 positions using an independent t-test. Percent accuracy was calculated. [Results] Inter-rater reliability was poor (position 1, k=1.04; position 2, k=0.016). Overall accuracy rate was 45.7% (117/256). Accuracy was 49.2% (63/128) and 42.2% (54/128) for testing position 1 and position 2 respectively. Mean distance palpated from the groove was M=2.58 mm (± 6.2 mm) for position 1 and M=3.77 mm (± 6.6 mm) for position 2. Inaccurate palpation occurred medially 72.3% (47/65) and 93.2% (69/74) in position 1 and position 2 respectively. [Conclusion] Results of this study did not support one arm position being more accurate over another for LHBT palpation.

Treatment of advanced metastatic castration-resistant prostate cancer after failure of approved therapy options remains challenging. Prostate-specific membrane antigen (PSMA)-targeting β- and α-emitters have been introduced, with promising response rates. Here, we present the first-to our knowledge-clinical data for PSMA-targeted α-therapy (TAT) using 225Ac-PSMA imaging and therapy (IT range, 6.0-8.5), with 1 cycle in 3 patients, 2 cycles in 7 patients, 4 cycles in 3 patients, and 5 cycles in 1 patient. No acute toxicity was observed during hospitalization. Baseline PSA was 112 ng/mL (range, 20.5-818 ng/mL). The best PSA response after TAT (a PSA decline ≥ 50%) was observed in 7 patients, and a PSA decline of any amount was observed in 11 patients. Three patients had no PSA decline at any time. A subgroup analysis of 11 patients with prior 177Lu-PSMA treatment showed any PSA decline in 8 patients and a decline of at least 50% in 5 patients. After TAT, grade 3 anemia was observed in 3 of the 14 patients, with 2 of them presenting with grade 2 anemia already at baseline. Grade 3 leukopenia was observed in 1 patient. Eight patients with preexisting xerostomia after 177Lu-PSMA showed no worsening after TAT. Newly diagnosed grade 1 or 2 xerostomia after TAT was observed in 5 patients. One patient reported no xerostomia at all. Conclusion: Our first clinical data for TAT using 225Ac-PSMA-I&T showed a promising antitumor effect in advanced metastatic castration-resistant prostate cancer. These results are highly comparable to data on 225Ac-PSMA-617 TAT.

Purpose Urinary stones can be successfully treated using a Holmium: Yttrium-Aluminum-Garnet (Ho: YAG) laser. Regarding success rates, laser pulse energy, frequency, and pulse width are well-known contributing factors. Whether the pulse shape might be a further factor influencing the laser efficiency is unclear. This study aimed to evaluate different modes of laser pulse shapes in a real-world setting. Materials and methods The Dornier Medilas® H Solvo (Wesling, Germany) was used in the treatment of ureter and kidney stones. Patients were randomized into standard pulse shape (SPS) and new pulse shape groups (NPS1; ureter) and (NPS2; kidney pelvis), depending on the stone localization. The primary endpoint was laser efficiency defined as mm³ stone destruction per overall operating time. Secondary endpoints encompassed number of stone recoveries and stone-free rate. Results Altogether 145 patients (24 SPS vs. 32 NPS1; 51 SPS vs. 38 NPS2) were included. No differences in sex, age, body mass index, stone localization and stone composition were found, except for preoperative stone size (133±95 [SPS] vs. 197±139 [NPS1] mm³; p=0.023) and (348±298 [SPS] vs. 525±429 [NPS2] mm³; p=0.042). Regarding the primary endpoint, a significant increase in laser efficiency could be detected for the NPS1 and NPS2 groups compared to the SPS groups (39.9±44.9 vs. 28.8±30.2 and 51.7±61.3 vs. 22.4±24.2 mm³/min [mean±standard deviation]). No statistically significant differences were found for secondary endpoints and perioperative complication rates. Conclusions Efficiency of the Ho: YAG laser can be positively influenced by different pulse shapes. This adds the variable of individualized intraoperative decision making.

ZusammenfassungWir berichten über einen multimorbiden 56-jährigen Patienten, welcher mit unbehandelter Tumorerkrankung nach Multiorganversagen auf die Palliativstation verlegt wurde. Aufgrund einer Eisenmangelanämie wurde eine Magen-Darm-Diagnostik zum Ausschluss einer gastrointestinalen Blutung durchgeführt. Diese Untersuchung zeigte ein Adenokarzinom des proximalen Kolons. Im Rahmen der Narkoseeinleitung zur Resektion des Tumors aspirierte der Patient und entwickelte einen schweren septischen Schock mit Multiorganversagen.Entsprechend der interdisziplinären Tumorboardempfehlung für Best Supportive Care (BSC) sowie dem vom Patienten gewünschten Abbruch der Therapie, erfolgte die Zuweisung auf die Palliativstation. Der voll urteilsfähige Patient hatte im Zuge der aus seiner Sicht dramatischen Ereignisse keine weiteren intensivmedizinischen Maßnahmen gewünscht.Im weiteren Verlauf der insgesamt fünfwöchigen Behandlung auf der Palliativstation stabilisierte sich der Patient. Dank intensiver Gespräche mit unterschiedlichen Professionen der Palliativmedizin über Therapieziele und die eigenen Präferenzen beschäftigte sich der Patient mit dem Lebensende und bereitete sich auf den Tod vor. Es zeigte sich, dass die Ablehnung weiterer intensivmedizinischer Maßnahmen aus Patientensicht keinen generellen Verzicht auf die Behandlung der Tumorerkrankung beinhaltete.Schließlich konnte bei vollständiger Rekonvaleszenz die geplante onkologische Therapie mit neoadjuvanter Chemotherapie und Tumorresektion erfolgreich durchgeführt werden.

Evidence about the influence of different business models (BMs) on the performance of small and medium enterprises (SMEs) is scarce and contradictory. In this paper, a meta-analytical study of the ...

Purpose:We compared the use of 11C-choline and 68Ga-prostate specific membrane antigen in men undergoing salvage lymph node dissection for nodal recurrent prostate cancer.Materials and Methods:The ...

Objective To investigate the effect of perioperative complications involving artificial urinary sphincter (AUS) implantation on rates of explantation and continence as well as health-related quality of life (HRQOL). Materials and methods Inclusion criteria encompassed non-neurogenic, moderate-to-severe stress urinary incontinence (SUI) post radical prostatectomy and primary implantation of an AUS performed by a high-volume surgeon (>100 previous implantations). Reporting complications followed the validated Clavien-Dindo scale and Martin criteria. HRQOL was assessed by the validated IQOL score, continence by the validated ICIQ-SF score. Statistical analysis included Chi (2) test, Mann-Whitney-U test, and multivariate regression models (p

Purpose This study evaluates the clinical use of the RUBY modular QA phantom for linac QA to validate the integrity of IGRT workflows including the congruence of machine isocenter, imaging isocenter, and room lasers. The results have been benchmarked against those obtained with widely used systems. Additionally, the RUBY phantom has been implemented to perform system QA (End‐to‐End testing) from imaging to radiation for IGRT‐based VMAT and stereotactic radiations at an Elekta Synergy linac. Material and Methods The daily check of IGRT workflow was performed using the RUBY phantom, the Penta‐Guide, and the STEEV phantom. Furthermore, Winston–Lutz tests was carried out with the RUBY phantom and a ball‐bearing phantom to determine the offsets and the diameters of the isospheres of gantry, collimator, and couch rotations, with respect to the room lasers and kV‐imaging isocenter. System QA was performed with the RUBY phantom and STEEV phantom for eight VMAT treatment plans. Additionally, the visibility of the embedded objects within these phantoms in the images and the results of CT and MR image fusions were evaluated. Results All systems used for daily QA of IGRT workflows show comparable results. Calculated shifts based on CBCT imaging agree within 1 mm to the expected values. The results of the Winston–Lutz test based on kV imaging (2D planar and CBCT) or room lasers are consistent regardless of the system tested. The point dose values in the RUBY phantom agree to the expected values calculated using algorithms in Masterplan and Monte Carlo engine in Monaco within 3% of the clinical acceptance criteria. Conclusion All the systems evaluated in this study yielded comparable results in terms of linac QA and system QA procedures. A system QA protocol has been derived using the RUBY phantom to check the IGRT‐based VMAT and stereotactic radiations workflow at an Elekta Synergy linac.

Purpose To report a single surgeon experience with one year follow-up after open ureteroplasty with buccal mucosa graft (OUBMG) in the rare situation of long segment proximal ureteral strictures. Materials and methods Four patients with long segment proximal ureteral stricture underwent OU-BMG between February and July 2017. Functional outcome was assessed by pre- and postoperative serum creatinine, ultrasound and renal scintigraphy as well as patient reported outcomes. Results Four patients with an average stricture length of 4 cm underwent OU-BMG between February and July 2017. No major postoperative complications occurred. Retrograde uretero-pyelography 6 weeks postoperatively revealed a watertight anastomosis followed by immediate emptying of the renal pelvis and ureter in all four patients. Ureteroscopy at this time showed a wide lumen with well-vascularized pink mucosa. After a mean follow-up time of 12.5 (12-14) months, postoperative serum creatinine was unimpaired. Renal scintigraphy revealed no signs of renal obstruction. With regard to intraoral surgery, no difficulties with mouth opening or intraoral dryness or numbness were reported. Conclusions For patients with long segment ureteral strictures OU-BMG is a safe technique with excellent surgical and functional outcomes. Hence, the application of this technique should be encouraged and regarded as one of the standard options in case of this rare problem.

Background Coronavirus disease 2019 (COVID-19) causes a range of illness severity. Mild illness has been reported, but whether illness severity correlates with infectivity is unknown. We describe the public health investigation of a mildly ill, nonhospitalized COVID-19 case who traveled to China. Methods The case was a Maricopa County resident with multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–positive specimens collected on 22 January 2020. Contacts were persons exposed to the case on or after the day before case diagnostic specimen collection. Contacts were monitored for 14 days after last known exposure. High-risk contacts had close, prolonged case contact (≥ 10 minutes within 2 m). Medium-risk contacts wore all US Centers for Disease Control and Prevention–recommended personal protective equipment during interactions. Nasopharyngeal and oropharyngeal (NP/OP) specimens were collected from the case and high-risk contacts and tested for SARS-CoV-2. Results Paired case NP/OP specimens were collected for SARS-CoV-2 testing at 11 time points. In 8 pairs (73%), ≥ 1 specimen tested positive or indeterminate, and in 3 pairs (27%) both tested negative. Specimens collected 18 days after diagnosis tested positive. Sixteen contacts were identified; 11 (69%) had high-risk exposure, including 1 intimate contact, and 5 (31%) had medium-risk exposure. In total, 35 high-risk contact NP/OP specimens were collected for SARS-CoV-2 testing; all 35 pairs (100%) tested negative. Conclusions This report demonstrates that SARS-CoV-2 infection can cause mild illness and result in positive tests for up to 18 days after diagnosis, without evidence of transmission to close contacts. These data might inform public health strategies to manage individuals with asymptomatic infection or mild illness.

Aims To comparatively analyse outcomes after ARGUS classic and ArgusT adjustable male sling implantation in a real-world setting. Methods Inclusion criteria encompassed: non-neurogenic, moderate-to-severe stress urinary incontinence (≥2 pads), implantation of an ARGUS classic or ArgusT male sling between 2010 and 2012 in a high-volume center (>150 previous implantations). Functional outcomes were assessed using daily pad usage, 24-hour pad testing, and International Consultation on Incontinence (ICIQ-SF) questionnaires. Continence was defined as zero pads per 24 hours. Complications were graded using Clavien-Dindo scale. For multivariate analysis, binary logistic regression models were used (P Results A total of 106 patients (n = 74 [ARGUS classic], n = 32 [ArgusT]) from four centers were eligible. Median follow-up was 44.0 months (24-64). Patient cohorts were well-balanced. We observed a statistical trend in favor of ARGUS classic regarding postoperative urine loss based on standardized 24-hour pad test (71 ± 162 g [ARGUS classic] vs 160 ± 180 g [ArgusT]); P = .066]. Dry rates were 33.3% (ARGUS classic) and 11.8% (ArgusT, P = .114). In multivariable analysis, ArgusT male sling could not be confirmed as an independent predictor of decreased success (OR, 0.587; 95% CI; 0.166-2.076, P = .408). There were no Clavien IV and V complications. Inguinal pain was significantly higher after ArgusT implantation (P = .033). Explantation rates were higher for ArgusT compared to ARGUS classic (14.0 vs 23.3%; P = .371). Longer device survival for the ARGUS classic male sling was observed in Kaplan-Meier analysis (P = .198). Conclusions In the largest comparative analysis of ARGUS classic and ArgusT male sling with the longest follow-up to date, we observed low continence rates with superior functional outcomes and decreased explantation rates after ARGUS classic implantation.

Purpose Introduction of robot-assisted radical prostatectomy (RARP) has revolutionized the therapeutic landscape of organ-confined prostate cancer (PCa). However, comparative analyses focused on health-related quality of life (HRQOL) after RARP and open retropubic prostatectomy (ORP) are sparse. Methods In the current retrospective analysis,inclusion criteria encompassed PSA ≤ 10 ng/ml, ≤ pT2c, ISUP ≤ 3, age ≤ 65 years, and preoperative continence. A propensity score-matched patient cohort [n = 418 (ORP: 209, RARP: 209)] was created and HRQOL was prospectively assessed based on validated questionnaires (EORTC QLQ-C30) preoperatively, 3 months, 12 months, and 24 months postoperatively. Primary endpoint was good general HRQOL based on previously published cut-off values. Erectile function was measured via IIEF-5, urinary continence via ICIQ-SF questionnaire. Multivariable analysis included binary logistic regression models (p

We offer theory and evidence about how the fit between firm experience (supply side) and consumer preferences (demand side) affects postentry performance into a new technology. Specifically, we explore different types of preentry experience (technological and market experience) and use different aspects of postentry performance to draw inferences about consumer heterogeneity. Preentry technological experience (same product and different consumers) helps firms attract a larger share of intensive users (aligning with early adopters) but only if they enter the market early when these adopters make decisions. Preentry market experience (different product and same consumers) helps firms attract a larger share of lighter users, consistent with characterizations of mass market users. Exploiting different components of firm performance in the global second-generation mobile telecommunications industry (average usage intensity and market penetration) allows us to articulate and identify the paths and mechanisms that allow preentry experience to affect postentry performance. The theory as well as important theoretical boundary conditions have implications for research on preentry experience, demand-side heterogeneity, and industry evolution.

Intrauterine growth restriction (IUGR) and low birth weight are risk factors for childhood asthma. Atopic march describes the progression from early dermatitis to asthma during life. Since inflammatory signaling is linked to increased airway resistance and lung remodeling in rats after IUGR, we queried if these findings are related to skin inflammatory response. Firstly, we induced IUGR in Wistar rats by isocaloric protein restriction during gestation. IUGR rats showed lower body weight at postnatal day 1 (P1), catch-up growth at P21, and similar body weight like controls at P90. At P1 and P90, mRNA of inflammatory as well as fibrotic markers and number of skin immune cells (macrophages) were increased after IUGR. Skin thymic stromal lymphopoietin (TSLP) mRNA at P1 and serum TSLP at P1 and P21 were elevated in IUGR. Moreover, IUGR impaired transepidermal water loss at P21 and P90. IUGR induced higher. Secondly, the increase of TEWL after Oxazolone treatment as a model of atopic dermatitis (AD) was greater in IUGR than in Co. Our data demonstrate an early inflammatory skin response, which is linked to persistent macrophage infiltration in the skin and impaired epidermal barrier function after IUGR. These findings coupled with elevated TSLP could underlie atopic diseases in rats after IUGR. KEY MESSAGES: • The present study shows that IUGR increases macrophage infiltration and induces an inflammatory and fibrotic gene expression pattern in the skin of newborn rats. • Early postnatal inflammatory response in the skin after IUGR is followed by impaired epidermal barrier function later in life. • IUGR aggravates transepidermal water loss in an experimental atopic dermatitis model, possibly through elevated TSLP in skin and serum. • Early anti-inflammatory treatment and targeting TSLP signaling could offer novel avenues for early prevention of atopic disorders and late asthma in high-risk infants.

Objective: To analyze decision-making in patients with male urinary incontinence (SUI) in centers of expertise. The artificial urinary sphincter (AUS) remains the gold standard for male patients with moderate to severe SUI but adjustable male slings are a minimally invasive treatment option with good results, hence without a high level of evidence regarding the optimal patient selection. Materials and Methods: In total, 220 patients (88 AUS; 132 adjustable slings) were investigated from the DOMINO database that underwent surgery between 2010 and 2012 in 5 urological departments that offer adjustable sling systems as well as AUS systems for patients with moderate to severe urinary incontinence. For statistical analysis, the Mann-Whitney U test was used to identify differences between both groups. Results: Patients selected for an adjustable male sling were less likely to have a neurological disease (5.3 vs. 9.1%; p = 0.030), a prior urethral stricture (22.7 vs. 50.0%; p = 0.001), a prior incontinence surgery (24.4 vs. 45.5%; p = 0.01), or a prior radiation therapy (26.5 vs. 40.1%; p = 0.001). The severity of preoperative incontinence was higher in patients selected for an AUS with a mean pad usage per day of 7.60 versus 5.80 (p < 0.001). Mean postoperative pad usage and patients’ subjective perception were comparable in both groups. Conclusion: In centers offering both options, the decision-making is mainly based upon presence of radiation therapy and previous failed incontinence surgery. Despite the more complex patient cohort selected for an AUS implantation with a possible impact on the postoperative outcome, the functional results seem to be comparable indicating a proper preoperative patient assessment and selection in this cohort.