Women in Irish urology: An examination of female representation amongst attendees of the Irish Society of Urology annual meeting (2008-2020).

BACKGROUND: There is underrepresentation of women at surgical conferences. We examine the representation of women in Irish urology by looking at gender balance within the Irish Society of Urology (ISU) conference. AIMS: ISU programmes over thirteen years from 2008 to 2020 were assessed and female representation in session chairs, guest speakers, poster and oral presentations identified. Gender distributions of authors for each year was examined. To investigate changes in female representation temporally, the period of this study (2008-2020) was subdivided and compared: 2008-2013 and 2014-2020. RESULTS: 76 sessions were presided over by 138 chairs, of which 6 (4.3%) were female. Eight conferences had zero female chairs. 62 guest lectures were given, 6 (9.6%) by women. Of total 340 poster and 434 oral presentations, women delivered 24.9% (0-47.5%) of posters and 31.6% (10.3-59.4%) of oral presentations. We found no significant difference in the percentage of female poster presentations between the time periods 2008-2013 (m = 18.2, sd = 13.7) and 2014-2020 (m = 34.3, sd = 17.8), t(11) = -1.4, p > 0.05. However, we found a significant difference in the percentage of female oral presentations between the periods 2008-2013 (m = 18.7, sd = 14.2) and 2014-2020 (m = 40.6, sd = 14.5), t(11) = -2.8, p < 0.05. CONCLUSIONS: Our study is the second to examine female representation in Irish urology. Session chairs and guest speakers were grossly overrepresented by males as were oral and poster presentations. Despite lacking female influence overall, in more recent years there was an increased representation of women. Societies should strive to increase female representation, as this perpetuates a positive feedback loop, encouraging future female trainees to pursue urological surgery.

Does instillation of lidocaine gel following flexible cystoscopy decrease the severity of post procedure symptoms? A randomised controlled trial assessing the efficacy of lidocaine gel post flexible cystoscopy.

OBJECTIVE: To assess whether instillation of lidocaine gel both before and after flexible cystoscopy is more effective at reducing post procedural symptoms than instillation of lidocaine gel pre flexible cystoscopy alone. We hypothesise that inadequate urethral dwell time and dilution of lidocaine gel by the irrigation fluid during flexible cystoscopy limits its anaesthetic efficacy. Only one other study has attempted to reduce bothersome urinary symptoms through an intervention after flexible cystoscopy. METHODS: This was a randomised controlled trial in which patients were randomised 1:1 to receive lidocaine gel pre and post flexible cystoscopy (treatment) or lidocaine gel pre flexible cystoscopy only (control). Patient-reported outcome measures were used to assess symptoms and quality of life prior to cystoscopy, on day 2 and day 7 post cystoscopy. RESULT: Fifty patients were divided equally between the treatment and control groups. There were no significant differences in baseline characteristics between the groups (p = 1.000). An overall symptoms variable was measured, though no significant difference was found in the distribution of responses between the groups at baseline, 2 or 7 days after the flexible cystoscopy (p = 0.423, 0.651,0.735). In the treatment group, 1 patient (4.0%) presented to a doctor for review following flexible cystoscopy, and 4 patients (16.0%) presented in the control group (p = 0.349). CONCLUSION: Initial study results suggest that post-operative lidocaine does not significantly limit the exacerbation of urinary symptoms following flexible cystoscopy; however, our results are not powered to detect a small difference. We do not recommend a change in practice based on our results.

The Management of Incidental Prostate Cancer Following TURP

Aims The aim of this study was to assess the incidence, management and outcomes of incidentally diagnosed prostate cancer following TURP. Methods A retrospective review was performed using the histopathological departments' database of all patients who underwent a TURP across two university teaching hospitals over a ten year period. Results During the study period, a total of 826 patients underwent a TURP. 72 (10.3%) had an incidental diagnosis of CaP following TURP. 46 (63.9%) were managed expectantly while 26 (36.1%) underwent active treatment. Overall mortality was 29.2% (n=21) while cancer specific mortality was 6.9% (n=5). All these patients were in the hormonal treatment sub-group. Conclusion Our study demonstrates an expectant approach is favourable in low risk disease. Curative treatment does need to be considered for younger patients with a long life expectancy or patients with higher risk disease.

OC-14 - Baseline D-dimer levels are predictive of recurrent venous thromboembolism (VTE) at 6 months in cancer patients with VTE treated with tinzaparin.

INTRODUCTION: VTE is a major complication in cancer patients. Despite treatment with low molecular weight heparin (LMWH), 9% will have recurrent VTE within 6 months. Measurement of plasma biomarkers in cancer patients receiving LMWH may be predictive of recurrent VTE or overall survival (OS). AIM: We conducted a single arm phase 2 study to evaluate the efficacy and safety of once daily tinzaparin for the initial treatment and extended prophylaxis of VTE in cancer patients. The study included a prospective analysis of plasma biomarkers D-dimer and IL-6 to assess whether these were predictive of recurrent VTE or OS. MATERIALS AND METHODS: Consecutive patients with active cancer diagnosed with a pulmonary embolism (PE) and/or proximal deep venous thrombosis (DVT) at the University of Southern California Norris Comprehensive Cancer Center, Los Angeles County Medical Center, or New York Presbyterian - Weill Cornell Medical Center were invited to participate in this study with a target enrollment of 100 patients. Key eligibility criteria included: age ≥18, ECOG score ≤2, adequate organ function, and ≥6 month estimated survival. Patients were treated with daily subcutaneously tinzaparin 175 U/kg for 6 months on study. Tinzaparin could be continued ≤1 year at the discretion of the treating physician. All patients who received ≥1 dose were evaluable for efficacy and safety. Primary study endpoints were recurrent VTE or major bleeding. Secondary outcome measures included OS and plasma biomarkers. Biomarkers were measured at baseline, 7 days, 1 month and 6 months after tinzaparin initiation. Patients who had baseline and 1 week or 1 month samples collected were included in the biomarker analysis. RESULTS: 97 patients were enrolled. 2 patients were ineligible. 8 patients did not have baseline or follow-up biomarkers completed. 87 patients were included in the analysis. 28 (32%) of patients completed≥6 months of tinzaparin. Major bleeding occurred in 2 patients. 11 patients had recurrent VTE at 6 months (3 PE, 7 DVT, 1 central venous thrombosis not associated with a catheter). Median baseline D-dimer level was 2759 ng/mL (range: 375-37,591). Median baseline IL-6 level was 9.4 pg/mL (range: 0.8-20.9). Baseline D-dimer>median was predictive of VTE recurrence at 6 months (p=.006). Baseline IL-6>median was not predictive of VTE recurrence at 6 months. Neither 1 month D-dimer or IL-6 levels were predictive of VTE recurrence at 6 months. D-dimer and IL-6 at baseline and at 1 month were not predictive of OS. CONCLUSIONS: In patients with active cancer and VTE treated with tinzaparin, baseline D-dimer levels above the median value were predictive of VTE recurrence at 6 months.

Risk of recurrent venous thromboembolism and major hemorrhage in cancer-associated incidental pulmonary embolism among treated and untreated patients: a pooled analysis of 926 patients.

UNLABELLED: ESSENTIALS: We performed a pooled analysis of 926 patients with cancer-associated incidental pulmonary embolism (IPE). Vitamin K antagonists (VKA) are associated with a higher risk of major hemorrhage. Recurrence risk is comparable after subsegmental and more proximally localized IPE. Our results support low molecular weight heparins over VKA and similar management of subsegmental IPE. BACKGROUND: Incidental pulmonary embolism (IPE) is defined as pulmonary embolism (PE) diagnosed on computed tomography scanning not performed for suspected PE. IPE has been estimated to occur in 3.1% of all cancer patients and is a growing challenge for clinicians and patients. Nevertheless, knowledge about the treatment and prognosis of cancer-associated IPE is scarce. We aimed to provide the best available evidence on IPE management. METHODS: Incidence rates of symptomatic recurrent venous thromboembolism (VTE), major hemorrhage, and mortality during 6-month follow-up were pooled using individual patient data from studies identified by a systematic literature search. Subgroup analyses based on cancer stage, thrombus localization, and management were performed. RESULTS: In 926 cancer patients with IPE from 11 cohorts, weighted pooled 6-month risks of recurrent VTE, major hemorrhage and mortality were 5.8% (95% confidence interval [CI] 3.7-8.3%), 4.7% (95% CI 3.0-6.8%), and 37% (95% CI 28-47%). VTE recurrence risk was comparable under low molecular weight heparins (LMWH) and vitamin K antagonists (VKAs) (6.2% vs. 6.4%; hazard ratio [HR] 0.9; 95% CI 0.3-3.1), while 12% in untreated patients (HR 2.6; 95% CI 0.91-7.3). Risk of major hemorrhage was higher under VKAs than under LMWH (13% vs. 3.9%; HR 3.9; 95% CI 1.6-10). VTE recurrence risk was comparable in patients with an subsegmental IPE and those with a more proximally localized IPE (HR 1.1; 95% CI 0.50-2.4). CONCLUSION: These results support the current recommendation to anticoagulate cancer-associated IPE with LMWH and argue against different management of subsegmental IPE.

Outcomes of pregnancies in women with suspected antiphospholipid syndrome.

OBJECTIVES: To evaluate maternal and neonatal outcomes in women suspected to have primary antiphospholipid syndrome (PAPS). METHODS: A cohort from the Nova Scotia Atlee Perinatal Database (n = 211034) was studied. A total of 58 women with antiphospholipid antibodies without a clinical diagnosis of rheumatologic disease were evaluated. We compared them to maternal and neonatal outcomes of women without rheumatologic disease or PAPS who delivered in Nova Scotia 1988-2008. RESULTS: With PAPS, mean maternal age was older; mean gestational age and mean neonatal birth weight were less. With bivariate analysis, maternal colonization and urinary tract infection with group B streptococcus, thromboembolic disease, thrombocytopenia and Caesarean birth were more frequent in the suspected PAPS group compared to the control. Among neonates, hyperbilirubinemia, anemia, apnea, intraventricular hemorrhage grade I and II, retinopathy of prematurity, bronchopulmonary dysplasia, neonatal intensive care unit admission, and assisted ventilation occurred more frequently with PAPS. Babies in PAPS group had a longer hospital stay (8.7 vs 3.9 days). Logistic regression analysis identified that PAPS was only associated with increased risks of preeclampsia (Odds Ratio (OR) 2.2; 95% Confidence Interval (CI) 1.1-4.3; P = 0.016), urinary tract infection (OR 2.2; 95% CI 1.1-4.6; P = 0.02), and prematurity (gestational age ≤37) (OR 2.2; 95% CI, 1.07-4.3, P = 0.03). Positive predictive values for pregnancy induced hypertension, urinary tract infection and prematurity in women who had suspected APS were 24.1%, 17.2% and 45.6% respectively. CONCLUSION: With suspected PAPS, risks for preeclampsia, urinary tract infection and prematurity are increased. Outcomes for babies are related to prematurity.

A series of patients on anti-TNF therapy referred to a multidisciplinary lung cancer service.

BACKGROUND: Biological therapies have significantly improved the quality of life of patients with aggressive collagen vascular diseases. Blocking TNF activity may potentially confer a higher malignant potential for patients. AIMS: To identify patients to whom anti-TNF therapies were recently prescribed and were referred to a multidisciplinary lung cancer service. METHODS: Retrospective review of patients over an 18-month period who were referred to a multidisciplinary lung cancer service. RESULTS: Three patients who underwent recent anti-TNF therapies and presented with solid organ tumours. All had significant additional risks for cancer including smoking and family history and active connective tissue diseases with a past history of immunosuppressive therapies. CONCLUSIONS: Our series highlights the potential malignant risk of anti-TNF theraphy to a general medical audience.

Chlamydial infection increases gonococcal colonization in a novel murine coinfection model.

Genital tract infections caused by Neisseria gonorrhoeae and Chlamydia trachomatis serovars D to K occur at high incidence in many areas of the world. Despite high rates of coinfection with these pathogens, investigations of host-parasite interactions have focused on each pathogen individually. We describe here a coinfection model in which female BALB/c mice were first infected with the mouse Chlamydia species C. muridarum and then inoculated with N. gonorrhoeae following treatment with water-soluble 17ß-estradiol to promote long-term gonococcal infection. Viable gonococci and chlamydiae were recovered for an average of 8 to 10 days, and diplococci and chlamydial inclusions were observed in lower genital tract tissue by immunohistochemical staining. Estradiol treatment reduced proinflammatory cytokine and chemokine levels in chlamydia-infected mice; however, coinfected mice had a higher percentage of vaginal neutrophils compared to mice infected with either pathogen alone. We detected no difference in pathogen-specific antibody levels due to coinfection. Interestingly, significantly more gonococci were recovered from coinfected mice compared to mice infected with N. gonorrhoeae alone. We found no evidence that C. muridarum increases gonococcal adherence to, or invasion of, immortalized murine epithelial cells. However, increased vaginal concentrations of inflammatory mediators macrophage inflammatory protein 2 and tumor necrosis factor alpha were detected in C. muridarum-infected mice prior to inoculation with N. gonorrhoeae concurrently with the downregulation of cathelicidin-related antimicrobial peptide and secretory leukocyte peptidase inhibitor genes. We conclude that female mice can be successfully infected with both C. muridarum and N. gonorrhoeae and that chlamydia-induced alterations in host innate responses may enhance gonococcal infection.

Unsuspected pulmonary emboli adversely impact survival in patients with cancer undergoing routine staging multi-row detector computed tomography scanning.

BACKGROUND: While symptomatic venous thromboembolism adversely impacts survival among cancer patients, the outcome of cancer patients with unsuspected pulmonary embolism (UPE) found on routine cancer staging multi-row detector computed tomography (MDCT) scans is unknown. OBJECTIVE: To determine whether UPE detected on routine staging MDCT scans impacts overall survival among cancer patients. PATIENTS AND METHODS: We performed a matched cohort study of cancer patients diagnosed with UPE on routine staging scans between May 2003 and August 2006. Two controls (n = 137) were individually matched by age (± 5 years), cancer type and stage for each UPE patient (n = 70). We used Cox's proportional hazard models to compare the mortality between UPE patients and their matched controls. RESULTS: The hazard ratio (HR) for death among UPE patients was 1.51 (95% CI 1.01-2.27, P = 0.048). Compared with their matched controls, patients with UPE more proximal than the subsegmental arterial branches had a HR for death at 6 months of 2.28 (95% CI 1.20-4.33, P = 0.011) and an overall HR of 1.70 (95% CI 1.06-2.74, P = 0.027). Survival among UPE patients with isolated subsegmental PE (ISSPE) was not significantly different than that of matched controls (HR 1.04 95% CI 0.44-2.39, P = 0.92). CONCLUSIONS: UPE identified more proximal than the subsegmental arterial branches has a significant negative impact on survival among cancer patients.

Neonatal outcomes with caesarean delivery at term.

OBJECTIVE: To estimate the impact of caesarean delivery on the incidence of selected neonatal outcomes. PATIENTS AND METHODS: A 15-year, population-based, cohort study (1988-2002) using the Nova Scotia Atlee Perinatal Database compared neonatal outcomes in term newborns born by spontaneous and assisted vaginal delivery, with newborns born by caesarean delivery, with and without labour, using multiple logistic regression. RESULTS: From a total of 142 929 deliveries, there were 27 263 caesarean deliveries, 61% of which were performed in labour. Relative risks were adjusted for year of birth, maternal age, parity, smoking, maternal weight at delivery, hypertensive diseases, diabetes, previous caesarean delivery, use of regional anaesthesia, induction of labour, gestational age at delivery and large and small for gestational age, where significant. Caesarean delivery in labour, but not caesarean delivery without labour, had increased risks for depression at birth and neonatal respiratory conditions compared with spontaneous or assisted vaginal delivery. Compared with spontaneous vaginal delivery and assisted vaginal delivery, the risk of major neonatal birth trauma was decreased for infants after caesarean delivery with labour (odds ratio (OR) = 0.34, 95% CI 0.21 to 0.56 and OR = 0.07, 95% CI 0.04 to 0.11, respectively) and caesarean delivery without labour (OR = 0.20, 95% CI 0.08 to 0.52 and OR = 0.04, 95% CI 0.02 to 0.10, respectively). CONCLUSION: Caesarean delivery in labour, compared with vaginal delivery, is more likely to be associated with an increased risk for respiratory conditions and depression at birth than caesarean delivery without labour. Caesarean delivery appears protective against neonatal birth trauma, especially when performed without labour.

Hose instability and wake generation by an intense electron beam in a self-ionized gas.

The propagation of an intense relativistic electron beam through a gas that is self-ionized by the beam's space charge and wakefields is examined analytically and with 3D particle-in-cell simulations. Instability arises from the coupling between a beam and the offset plasma channel it creates when it is perturbed. The traditional electron hose instability in a preformed plasma is replaced with this slower growth instability depending on the radius of the ionization channel compared to the electron blowout radius. A new regime for hose stable plasma wakefield acceleration is suggested.

Plasma wakefield acceleration in self-ionized gas or plasmas.

Tunnel ionizing neutral gas with the self-field of a charged particle beam is explored as a possible way of creating plasma sources for a plasma wakefield accelerator [Bruhwiler et al., Phys. Plasmas (to be published)]. The optimal gas density for maximizing the plasma wakefield without preionized plasma is studied using the PIC simulation code OSIRIS [R. Hemker et al., in Proceeding of the Fifth IEEE Particle Accelerator Conference (IEEE, 1999), pp. 3672-3674]. To obtain wakefields comparable to the optimal preionized case, the gas density needs to be seven times higher than the plasma density in a typical preionized case. A physical explanation is given.

Prediction of DNA single-strand conformation polymorphism: analysis by capillary electrophoresis and computerized DNA modeling.

We have analyzed previously three representative p53 single-point mutations by capillary-electrophoresis single-strand conformation polymorphism (CE-SSCP). In the current study, we compared our CE-SSCP results with the potential secondary structures predicted by an RNA/DNA-folding algorithm with DNA energy rules, used in conjunction with a computer analysis workbench called STRUCTURELAB. Each of these mutations produces measurable shifts in CE migration times relative to wild type. Using computerized folding analysis, each of the mutations was found to have a conformational difference relative to wild type, which accounts for the observed differences in CE migration. Additional properties exhibited in the CE electropherograms were also explained using the computerized analysis. These include the appearance of secondary peaks and the temperature dependence of the electrophoretic patterns. The results yield insight into the mechanism of SSCP and how the conditions of this measurement, especially temperature, may be optimized to improve the sensitivity of the SSCP method. The results may also impact other diagnostic methods, which would benefit by a better understanding of DNA single-strand conformation polymorphisms to optimize conditions for enzymatic cleavage and DNA hybridization reactions.

Distinct roles of the equatorial and polar cortices in the cleavage of adherent cells.

Over the past 100 years, many models have been proposed and tested for cytokinesis [1]. There is strong evidence that the equator represents a unique region that receives cleavage signals from the mitotic spindle [2, 3]. The nature of such a signal and the mechanism of cleavage, however, remain poorly understood. To probe the contribution of different cortical regions in the cleavage of cultured epithelial cells, we applied cytochalasin D (CD), a known inhibitor of cytokinesis [4], in a highly localized manner to different regions of dividing NRK cells. Surprisingly, equatorial application of CD not only allowed cytokinesis to complete but also appeared to facilitate the process. Conversely, local application of CD near the polar region caused inhibition of cytokinesis. Our results suggest a mechanism that involves global coordination of cortical activities, including controlled cortical disassembly along the equator and possibly global cortical contraction.

Translocated EspF protein from enteropathogenic Escherichia coli disrupts host intestinal barrier function.

The mechanisms by which enteropathogenic Escherichia coli (EPEC), an important cause of diarrhea among infants in developing countries, induce symptoms are not defined. EPEC have a type III secretion system required for characteristic attaching and effacing changes that modify the cytoskeleton and apical surface of host cells. Infection of polarized intestinal epithelial cell monolayers by EPEC leads to a loss of transepithelial electrical resistance, which also requires the type III secretion system. We demonstrate here that EspF, a protein that is secreted by EPEC via the type III secretion system, is not required for quantitatively and qualitatively typical attaching and effacing lesion formation in intestinal epithelial cells. However, EspF is required in a dose-dependent fashion for the loss of transepithelial electrical resistance, for increased monolayer permeability, and for redistribution of the tight junction-associated protein occludin. Furthermore, the analysis of EPEC strains expressing EspF-adenylate cyclase fusion proteins indicates that EspF is translocated via the type III secretion system to the cytoplasm of host cells, a result confirmed by immunofluorescence microscopy. These studies suggest a novel role for EspF as an effector protein that disrupts intestinal barrier function without involvement in attaching and effacing lesion formation.