Late-instar monarch caterpillars sabotage milkweed to acquire toxins, not to disarm plant defence.

Sabotaging milkweed by monarch caterpillars (Danaus plexippus) is a famous textbook example of disarming plant defence. By severing leaf veins, monarchs are thought to prevent the flow of toxic latex to their feeding site. Here, we show that sabotaging by monarch caterpillars is not only an avoidance strategy. While young caterpillars appear to avoid latex, late-instar caterpillars actively ingest exuding latex, presumably to increase sequestration of cardenolides used for defence against predators. Comparisons with caterpillars of the related but non-sequestering common crow butterfly (Euploea core) revealed three lines of evidence supporting our hypothesis. First, monarch caterpillars sabotage inconsistently and therefore the behaviour is not obligatory to feed on milkweed, whereas sabotaging precedes each feeding event in Euploea caterpillars. Second, monarch caterpillars shift their behaviour from latex avoidance in younger to eager drinking in later stages, whereas Euploea caterpillars consistently avoid latex and spit it out during sabotaging. Third, monarchs reared on detached leaves without latex sequestered more cardenolides when caterpillars imbibed latex offered with a pipette. Thus, we conclude that monarch caterpillars have transformed the ancestral 'sabotage to avoid' strategy into a 'sabotage to consume' strategy, implying a novel behavioural adaptation to increase sequestration of cardenolides for defence.

A description and sensitivity analysis of the ArchMatNet agent-based model.

Archaeologists cannot observe face-to-face interactions in the past, yet methods derived from the analyses of social networks are often used to make inferences about patterns of past social interactions using material cultural remains as a proxy. We created the ArchMatNet agent-based model to explore the relationship between networks built from archaeological material and the past social networks that generated them. It was designed as an abstract model representing a wide variety of social systems and their dynamics: from hunter-gatherer groups to small-scale horticulturalists. The model is highly flexible, allowing agents to engage in a variety of activities (e.g., group hunting, visiting, trading, cultural transmission, migration, seasonal aggregations, etc.), and includes several parameters that can be adjusted to represent the social, demographic and historical dynamics of interest. This article examines how sensitive the model is to changes in these various parameters, primarily by relying on the one-factor-at-a-time (OFAT) approach to sensitivity analysis. Our purpose is for this sensitivity analyses to serve as a guide for users of the model containing information on how the model works, the types of agents and variables included, how parameters interact with one another, the model outputs, and how to make informed choices on parameter values.

Absence of detrusor muscle in TUR-BT specimen - can we predict who is at highest risk?

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.

Identification of the Tumor Infiltrating Lymphocytes (TILs) Landscape in Pure Squamous Cell Carcinoma of the Bladder.

Background: Tumor infiltrating lymphocytes (TILs) are known as important prognostic biomarkers and build the fundament for immunotherapy. However, the presence of TILs and its impact on outcome in pure squamous cell carcinoma (SCC) of the bladder remains uncertain. Methods: Out of 1600 patients undergoing radical cystectomy, 61 patients revealed pure bladder SCC in the final histopathological specimen. Retrospectively, immunohistochemical staining was performed on a subset of TILs (CD3+, CD4+, CD8+, CD20+). Endpoints were overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS). The Kaplan−Meier method was used to evaluate survival outcomes. Results: Strong infiltration of CD3+ was found in 27 (44%); of CD4+ in 28 (46%); of CD8+ in 26 (43%); and of CD20+ in 27 tumors (44%). Improved OS was observed for strong CD3+ (p < 0.001); CD4+ (p = 0.045); CD8+ (p = 0.001); and CD20+ infiltration (p < 0.001). Increased rates of PFS were observed for CD3+ (p = 0.025) and CD20+ TILs (p = 0.002). In multivariate analyses, strong CD3+ (HR: 0.163, CI: 0.044−0.614) and strong CD8+ TILs (HR: 0.265, CI: 0.081−0.864) were revealed as predictors for OS and the strong infiltration of CD20+ cells (HR: 0.095, CI: 0.019−0.464) for PFS. Conclusions: These first results of TILs in bladder SCC revealed predictive values of CD3+, CD8+ and CD20+.

A matter of size? Health-related quality of life after radical prostatectomy for patients with giant prostates.

BACKGROUND: Evidence regarding the impact of giant prostate volume (PV) on outcome after radical prostatectomy (RP) is controversial with a lack of evidence on the impact of PV on health-related quality of life (HRQOL). We aimed to assess the impact of giant PV on HRQOL and functional outcomes for men with prostate cancer (PC) undergoing RP. METHODS: Giant PV was defined based on the 95th percentile of PV measured by specimen weight of 3929 patients that underwent RP between 2013 and 2018 in a large tertiary care center. A propensity score-matched analysis of 929 men treated with RP for PC (n = 184 with PV ≥ 100 cm3 , n = 745 with PV < 100 cm3 ) was conducted. Primary endpoint was the impact of giant PV on HRQOL (based on EORTC QLQ-C30) assessed with binary logistic regression and Cox proportional hazard model. Secondary endpoint was the impact of PV on oncological- and functional outcome. RESULTS: Median follow-up was 24 months. Median PV, measured by specimen-weight, was 58 cm3 . We found no significant differences in median general HRQOL (p = .183), giant PV was not associated with better HRQOL (odds ratio [OR], 1.54; 95% confidence interval [CI], 0.96-2.47; p = .075). No significant differences were found regarding continence recovery (hazard ratio [HR], 0.956; 95% CI, 0.771-1.185; p = .682), median International Consultation of Incontinence Questionnaire-Short-Form (ICIQ-SF) scores (p = .062) or potency rates (p = .151). Giant PV did not significantly impair biochemical recurrence-free survival (HR, 0.968; 95% CI, 0.651-1.439; p = .871). CONCLUSIONS: For patients undergoing RP, giant PV was not associated with adverse HRQOL outcomes. We found no significant impact of PV on continence rates, potency rates, and biochemical recurrence-free survival. Hence, RP is an efficient cancer treatment for men even with giant PV.

Impact of previous transurethral prostate surgery on health-related quality of life after radical prostatectomy: Does the interval between surgeries matter?

PURPOSE: To assess the impact of previous transurethral surgery for benign prostate enlargement (BPE) and time interval between procedures on functional outcomes and health-related quality of life (HRQOL) after radical prostatectomy (RP). METHODS: A propensity score-matched patient cohort [n = 685, (513 without previous BPE surgery, 172 with BPE surgery)] was created and HRQOL was pre- and postoperatively assessed using validated questionnaires (EORTC QLQ-C30). Urinary continence was measured via ICIQ-SF questionnaire and pad usage. Multivariable analysis included binary logistic and Cox regression models (p < 0.05). RESULTS: Median follow-up was 18 months. There was no significant difference in recurrence-free survival in multivariate analysis (HR 0.66, 95%CI 0.40-1.07, p = 0.093). We observe higher mean ICIQ-SF scores (5.7 vs. 8.2, p < 0.001) and daily pad usage (1.3 vs. 2.5, p < 0.001), and decreased continence recovery (OR 0.46, 95%CI 0.30-0.71, p < 0.001) for patients with BPE surgery. Postoperative general HRQOL scores were significantly lower for patients with previous BPE surgery (70.6 vs. 63.4, p = 0.003). In multivariate analysis, continence recovery (OR 5.19, 95%CI 3.10-8.68, p < 0.001) but not previous BPE surgery (0.94, 0.57-1.54, p = 0.806) could be identified as independent predictors of good general HRQOL. There was no significant correlation between time interval between both surgeries and continence (p = 0.408), and HRQOL (p = 0.386) outcomes. CONCLUSIONS: We observe favourable continence outcomes for patients without previous BPE surgery. Our results indicate that RP can be safely performed after transurethral BPE surgery, regardless of the time interval between both interventions.

The natural course of urinalysis after urinary diversion.

OBJECTIVE: To evaluate the impact of urinary diversion on regular features of urinalysis and to screen for risk factors of infection-related complications. METHODS: We conducted a retrospective, single-centre study of 429 patients who underwent open radical cystectomy. Patients were followed for 12 months and data of the complete urinalyses were analysed at three pre-defined time points. RESULTS: Two weeks after surgery, dipstick testing with positive reactions for leukocyte esterase and haemoglobin were confirmed in 80.7% and 80% after ileal conduit (IC) and orthotopic ileal neobladder (NB), respectively. Every patient was positive for these parameters 12 months after surgery. Correspondingly, the microscopic examination detected leukocytes (84% vs. 85.4%), erythrocytes (82.8% vs. 83.8%) and bacteria (94.3% vs. 96.8%) following IC and NB reconstruction. After 12 months, all parameters were positive irrespective of the type of urinary diversion. Two weeks after surgery positive urine cultures were obtained in more than 50% of cases after IC (52.5%) and NB (60.5%) (p > 0.05). All urine cultures were positive after 12 months with significantly more poly-microbial results found after NB (81.3%) compared with IC (67.2%) (p = 0.018). In univariate and multivariate logistic regression analysis the presence of hydronephrosis was independently associated with the occurrence of infectious complications (OR 4.2; CI 95% 1.525-11.569; p = 0.006). CONCLUSION: A positive urinalysis is a common finding after urinary diversion. Hydronephrosis is a serious risk factor with respect to infection-related complications. The simple fact of a positive urinalysis does not warrant antimicrobial treatment.

Predictive clinical features for negative histopathology of MRI/Ultrasound-fusion-guided prostate biopsy in patients with high likelihood of cancer at prostate MRI: Analysis from a urologic outpatient clinic1.

OBJECTIVE: The aim of this study was to evaluate clinical features associated with benign histopathology of Prostate Imaging Reporting and Data System (PI-RADS) category 4 and 5 lesions. MATERIALS AND METHODS: Between March 2015 and November 2020, 1161 patients underwent mpMRI/Ultrasound-fusion-guided prostate biopsy (FBx) and concurrent 12-core systematic prostate biopsy (SBx) at the Department of Urology of the Ludwig-Maximilians-University of Munich, Germany. 848/ 1161 (73%) patients presented with either PI-RADS 4 or 5 index lesion and were retrospectively evaluated. Multivariate analysis was performed to evaluate clinical parameters associated with a negative outcome of PI-RADS 4 or 5 category lesions after FBx. Area under the receiver operating characteristics (ROC) curve (AUC) was conducted using ROC-analysis. RESULTS: 676/848 (79.7%) patients with either PI-RADS 4 or 5 index lesion were diagnosed with prostate cancer (PCa) by FBx and 172/848 (20.3%) patients had a negative biopsy (including the concurrent systematic prostate biopsy), respectively. Prostate volume (P-Vol) (OR 0.99, 95% CI = 0.98-1.00, p = 0.038), pre-biopsy-status (OR 0.48, 95% CI = 0.29-0.79, p = 0.004) and localization of the lesion in the transitional zone (OR 0.28, 95% CI = 0.13-0.60, p = 0.001) were independent risk factors for a negative outcome of FBx. Age (OR 1.09, 95% CI = 1.05-1.13, p < 0.001) and PSA density (PSAD) (OR 75.92, 95% CI = 1.03-5584.61, p = 0.048) increased the risk for PCa diagnosis after FBx. The multivariate logistic regression model combining all clinical characteristics achieved an AUC of 0.802 (95% CI = 0.765-0.835; p < 0.001) with a sensitivity and specificity of 66% and 85%. CONCLUSION: Lesions with high or highly likelihood of PCa on multiparametric magnetic resonance imaging (mpMRI) but subsequent negative prostate biopsy occur in a small amount of patients. Localization of the lesion in the transitional zone, prostate volume and prebiopsy were shown to be predictors for benign histopathology of category 4 or 5 lesions on mpMRI. Integration of these features into daily clinical routine could be used for risk-stratification of these patients after negative biopsy of PI-RADS 4 or 5 index lesions.

Multiparametric magnetic resonance imaging and multiparametric magnetic resonance imaging-guided biopsy in the diagnostic pathway of prostate cancer.

Multiparametric magnetic resonance imaging (mpMRI) of the prostate and mpMRI-guided biopsy have proved to be a valuable part of the diagnostic pathway for prostate cancer. This review reports on the current results in terms of clinical performance of these diagnostic tools and their role in clinical decision-making.

Health-related quality of life after open and robot-assisted radical prostatectomy in low- and intermediate-risk prostate cancer patients: a propensity score-matched analysis.

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 < 0.05). RESULTS: Open retropubic prostatectomy and RARP cohorts were well balanced. General HRQOL was significantly higher for ORP compared to RARP after 3 months (70.1 vs. 61.6, p = 0.001), but not at the remaining follow-up time points. There were no significant differences for the remaining QLQ-C30 functioning and symptom scores. In multivariable analysis stratified for IIEF-5 and ICIQ-SF scores and surgeon experience, RARP could be confirmed as a marginally independent predictor for lower ratios of good general HRQOL after 3 months (OR 0.464, 95% CI 0.215-0.999; p = 0.050) without any differences at the remaining time points. CONCLUSIONS: The current study addresses various HRQOL outcomes over a postoperative period of up to 2 years in a homogenous propensity score-matched contemporary cohort. Marginally better general HRQOL outcomes could be detected for ORP compared to RARP 3 months postoperatively.