bluuebunny/crossref_metadata_2025 huggingface dataset:
Sperm immunization and rat spermatogenesis: Dysfunctional blood‐testis barrier and perturbed Sertoli cell cytoskeleton
Authors: Noguchi Junko , Kaneko Hiroyuki , Ikeda Mitsumi , Kikuchi Kazuhiro , Dang‐Nguyen Thanh Quang , Furusawa Tadashi
Published: December 2020

Background

Male infertility may be due in part to autoimmune orchitis. Experimental models of autoimmune orchitis have yielded valuable information for understanding the underlying pathogenesis. However, previous rodent models show progressive inflammatory cell infiltration, thus differing from human cases.

Objective

We have established an immunization procedure that induces defective spermatogenesis in rats. Here, we examined the affected testes to clarify the pathogenetic mechanism responsible.

Materials and methods

Male rats received two subcutaneous injections of spermatozoa in LPS‐supplemented oil‐based adjuvant. The testes were collected when atrophy was detected by palpation in order to explore the acute phase of the defect. The blood‐testis barrier (BTB) permeability was examined in a biotin tracer experiment. Testes were examined immunohistochemically using antibodies against TNFα+ and ED1 (a macrophage marker) to detect inflammatory cells. Antibodies against proteins related to tight and gap junctions, desmosomes, and the Sertoli cell cytoskeleton were also employed. The expression of junction‐related molecules and vimentin was also examined by Western blotting and RT‐PCR.

Results

Immunohistochemistry revealed TNFα+ and ED1+ cells scattered in the interstitium. TNFα+ cells, but not ED1+ macrophages, were associated with seminiferous tubules in the affected testis. The tracer experiment demonstrated dysfunction of the BTB. Immunohistochemistry revealed delocalization of claudin 11 and tight junction protein 1. Positive immunoreactivity for connexin 43 (a major gap junction protein) and desmoglein 2 (a major desmosome protein) was reduced, probably resulting in germ cell exfoliation. F‐actin and vimentin showed aberrant distribution in the seminiferous epithelium, and expression of vimentin was upregulated in the affected testis.

Conclusion

The observed pathological characteristics demonstrate how inflammatory cells influence Sertoli cells, leading to impaired spermatogenesis, and suggest that this sperm immunization method provides a new rat model of autoimmune orchitis.
Forest structure and biomass in post‐agricultural forests: Lessons learned with new spatial tools
Authors: Brubaker Kristen , Cosentino Bradley
Published: December 2020

Questions: With calls for afforestation to sequester carbon due to climate change, agricultural land will be converted to forests in the near future. Little is known about how the ecosystem services of reforested landscapes with an agricultural land‐use history will differ from reference forests. Our objectives were to (i) test the hypothesis that forests with a history of agricultural land use can provide the same carbon storage and biomass ecosystem services as adjacent reference forests, given some recovery time; (ii) explore whether there is a lag in the recovery of forest community composition due to prior agricultural land use; and (iii) demonstrate how remote‐sensing methods can improve our understanding of land‐use legacies at large spatial scales.

Location: Finger Lakes National Forest, NY, USA.

Methods: Using historic air photos, landscape‐scale lidar, and field surveys, we compared differences in biomass storage, forest structure, and vegetation communities between reference forests and post‐agricultural forests at different stages of regeneration in the Finger Lakes National Forest, New York, USA. We also used lidar to create a spatial model of biomass across the landscape to analyze the spatial distribution of biomass across our study area.

Results: We found biomass and forest structure in post‐agricultural forests generally recovered to levels typical of reference forests within 50 years of abandonment. Conversely, we found the composition of woody and herbaceous communities still varied between reference and post‐agricultural forests after 50 years of abandonment.

Conclusions: Collectively our results indicate afforestation efforts can be effective for carbon sequestration at early stages of forest succession. Our spatial model of biomass indicated that biomass levels can be low in forests with extensive edge. Further research is needed to understand how contemporary landscape structure interacts with legacy effects of agriculture to affect biomass and other ecosystem services.
Maternal smoking during pregnancy: Trends and determinants in the conception to community study
Authors: Ezegbe Chigozie , Neil Amanda L. , Magnussen Costan G. , Chappell Katherine , Judd Fiona , Wagg Fiona , Gall Seana
Published: December 2020

Background

Despite earlier declines, maternal smoking during pregnancy continues to be a public health problem. We examined trends and factors associated with maternal smoking during and between pregnancy over six years.

Methods

Participants were 27 532 pregnant women in Tasmanian public hospitals whose smoking status was gathered by midwives during perinatal care between July 2008 and June 2014. Generalized linear modeling was used to examine the trends in prevalence of maternal smoking over time and factors associated with change in smoking status both within and between pregnancies.

Results

Smoking during pregnancy decreased from 25.9% in 2008 to 16.4% in 2014 (57.9% decline). Multivariable regression analysis suggested that maternal alcohol consumption during pregnancy, living in a highly socioeconomically disadvantaged area, and being an Aboriginal or Torres Strait Islander significantly increased the risk of maternal smoking during pregnancy. Being older, married, or in a de facto relationship, and intending to breastfeed were associated with reduced risk of smoking during pregnancy. Between index (first birth recorded in data set) and last pregnancy, 35.1% of smokers quit, but 5.1% of nonsmokers started smoking. Only 8.1% of mothers who smoked during the first half of pregnancy quit by the second half.

Conclusions

Maternal smoking during pregnancy is decreasing. To sustain the decline, preventive efforts must address the role of social determinants of health (eg, mothers who drink alcohol, live in highly disadvantaged areas, are younger and single) among women who smoke during pregnancy.
From gains to losses: Age‐related differences in decisions under risk in a non‐monetary gambling task
Authors: Depping Miriam K. , Best Ryan , Freund Alexandra M.
Published: December 2020

Lifespan theory suggests a shift from a primary orientation towards attaining gains in young adulthood to preventing losses in older adulthood. The current research tested if this motivational shift is reflected in behavioural and emotional responses to risks in non‐monetary gains and losses. Study 1 established in a sample of N = 168 younger (18–30 years) and older adults (65–79 years) that a non‐monetary gambling task was experienced similarly by the age groups with respect to arousal and valence of the task, and the willingness to continue playing. In Study 2 (N = 83), differences between young (18–30 years) and older (64–85 years) adults’ risk‐taking in this non‐monetary gambling task with mixed gambles were tested while assessing physiological responses (event‐related heart rate change) to gain and loss feedback. Behavioural – but not physiological – results confirm hypotheses derived from a lifespan motivational framework regarding age‐differential effects of gains and losses.
Percutaneous microwave ablation of renal masses in a UK cohort
Authors: John Joseph B. , Anderson Moira , Dutton Thomas , Stott Mark , Crundwell Malcolm , Llewelyn Rhys , Gemmell Andrew , Bufacchi Rory , Spiers Alexander , Campain Nicholas
Published: December 2020

Objectives

To report a tertiary referral centre’s experience of microwave ablation (MWA) for suspected renal cell carcinoma (RCC), describing complications and oncological outcomes.

Patients and Methods

Consecutive MWA procedures (n = 113) for renal masses (October 2016 to September 2019) were maintained on a prospective database. Data describing patient, disease, procedure, complications, and oncological outcomes were analysed.

Results

The median (range) age was 68 (33–85) years, 73% were male, and the median Charlson Comorbidity Index was 0. The median (interquartile range [IQR]) tumour diameter was 25 (20–32) mm. In all, 95% had renal mass biopsy, with histologically confirmed cancer in 75%. The median (IQR) R.E.N.A.L. (Radius, Exophytic/Endophytic, Nearness, Anterior/Posterior, Location) nephrometry score was 7 (6–8). The median ablation time was 6 min and length of stay was 1 day for 95% of the patients. Clavien–Dindo complication Grades I, II, IIIb and IV occurred in 18%, 1.8%, 0.9% and 0.9%, respectively. The median follow‐up was 12 months and the median (IQR) renal function change was −4 (−18 to 0)%. One patient (0.9%) had local recurrence, treated with re‐ablation; two developed metastatic progression; and two (1.8%) had indeterminate findings on follow‐up (one lung nodule and one possible local recurrence), managed with ongoing protocolised computed tomography surveillance. Post‐procedure complications were associated with total ablation time (odds ratio [OR] 1.152/min, 95% confidence interval [CI] 1.040–1.277) and total ablation energy (OR 1.017/kJ, 95% CI 1.001–1.033).

Conclusions

We describe the largest UK series of MWA treatment for T1a/small T1b renal masses to date. MWA was well tolerated, with 95% discharged the following day and low complication/re‐admission rates. Current follow‐up demonstrates favourable disease control. MWA appears to be safe and effective and should be considered in future prospective comparisons of treatments for T1a/small T1b renal masses.
NeuroSAFE frozen section during robot‐assisted radical prostatectomy: peri‐operative and histopathological outcomes from the NeuroSAFE PROOF feasibility randomized controlled trial
Authors: Dinneen Eoin , Haider Aiman , Grierson Jack , Freeman Alex , Oxley Jon , Briggs Tim , Nathan Senthil , Williams Norman R. , Brew‐Graves Chris , Persad Raj , Aning Jon , Jameson Charles , Ratynska Marzena , Ben‐Salha Imen , Ball Rhys , Clow Rosie , Allen Clare , Heffernan‐Ho Daniel , Kelly John , Shaw Greg
Published: December 2020

Objectives

To report on the methods, peri‐operative outcomes and histopathological concordance between frozen and final section from the NeuroSAFE PROOF feasibility study (NCT03317990).

Patients and Methods

Between May 2018 and March 2019, 49 patients at two UK centres underwent robot‐assisted radical prostatectomy (RARP). Twenty‐five patient were randomized to NeuroSAFE RARP (intervention arm) and 24 to standard RARP (control arm). Frozen section was compared to final paraffin section margin assessment in the 25 patients in the NeuroSAFE arm. Operation timings and complications were collected prospectively in both arms.

Results

Fifty neurovascular bundles (NVBs) from 25 patients in the NeuroSAFE arm were analysed. When analysed by each pathological section (n= 250, average five per side), we noted a sensitivity of 100%, a specificity of 99.2%, and an area under the curve (AUC) of 0.994 (95% confidence interval [CI] 0.985 to 1;P≤0.001). On an NVB basis (n= 50), sensitivity was 100%, specificity was 92.7%, and the AUC was 0.963 (95% CI 0.914 to 1;P≤0.001). NeuroSAFE RARP lasted a mean of 3 h 16 min (knife to skin to off table, 95% CI 3 h 2 min–3 h 30 min) compared to 2 h 4 min (95% CI 2 h 2 min–2 h 25 min;P≤0.001) for standard RARP. There was no morbidity associated with the additional length of operating time on in the NeuroSAFE arm.

Conclusion

This feasibility study demonstrates the safety, reproducibility and excellent histopathological concordance of the NeuroSAFE technique in the NeuroSAFE PROOF trial. Although the technique increases the duration of RARP, this does not cause short‐term harm. Confirmation of feasibility has led to the opening of the fully powered NeuroSAFE PROOF randomized controlled trial, which is currently under way at four sites in the UK.
Perioperative outcomes and cost of robotic vs open simple prostatectomy in the modern robotic era: results from the National Inpatient Sample
Authors: Bhanvadia Raj , Ashbrook Caleb , Gahan Jeffery , Mauck Ryan , Bagrodia Aditya , Margulis Vitaly , Lotan Yair , Roehrborn Claus , Woldu Solomon
Published: December 2020

Objectives

To perform a comparative analysis of perioperative outcomes and hospitalisation cost between open (OSP) and robot‐assisted simple prostatectomy (RASP) for treatment of benign prostatic hyperplasia (BPH) using the National Inpatient Sample (NIS) in the contemporary robotic era.

Materials and Methods

The NIS was queried for cases of OSP and RASP for the treatment of BPH between 2013 and 2016. Perioperative complications, unadjusted hospital cost and length of stay (LOS) were compared between RASP and OSP. Smoothed linear regression curves comparing hospitalisation cost by increasing LOS was stratified by surgical approach to identify point of cost equivalency between RASP and OSP. Multivariable linear regression analysis was used to construct a hospitalisation cost model to examine the contribution of the robotic approach and LOS to hospitalisation cost.

Results

The total analytical cohort included 2551 OSP and 704 RASP procedures. Patients undergoing RASP were younger, at a median (interquartile range [IQR]) age of 68 (63–73) vs 71 (65–77) years, and with less comorbidity (76.8% vs 86.5%, P < 0.01). RASP was associated with fewer total complications (11.1% vs 29.2%, P < 0.01) and a greater likelihood of routine discharge to home rather than another facility (88.9% vs 76.7%, P < 0.01). While LOS was shorter with RASP (median [IQR], 2 [1–3] vs 4 [3–6] days, P < 0.01), total unadjusted hospitalisation cost (in United States dollars) was greater (median [IQR], $10 855 [$7965–$15 675] vs $13 467 [$10 572–$17 722], P < 0.01). Presence of any complication increased both LOS and hospitalisation cost (P < 0.01). Linear regression modelling determined the point of cost equivalence between RASP staying a median of 2 days was an OSP case staying between 5 and 6 days. On multivariable regression analysis, the robotic approach contributed an additional $6175 (P < 0.01) to the cost model, whereas each additional day of hospitalisation contributed $1687 (P < 0.01), suggesting LOS would need to be 3–4 days shorter with RASP to offset surgical costs of the robot.

Conclusions

While RASP appears to have significantly better perioperative complication rates with shorter LOS and likely discharge to home, total hospitalisation cost remained greater, likely related to upfront operative costs. While this retrospective study is limited by selection bias for patients undergoing RASP, the benefits of improved convalescence, discharge to home, and lower rate of perioperative complications appear to justify performance of RASP in an experienced pelvic robotic centre despite relatively greater hospitalisation cost if referral to an experienced holmium laser enucleation of the prostate centre is not feasible.
Functional and oncological outcomes of salvage cryosurgery for radiorecurrent prostate cancer
Authors: Exterkate Leonie , Peters Max , Somford Diederik M. , Vergunst Henk
Published: December 2020

Objectives

To evaluate the oncological and functional outcomes of salvage cryosurgery (SCS) for radiorecurrent prostate cancer (rrPCa).

Patients and Methods

A total of 169 consecutive patients with biopsy confirmed rrPCa were retrospectively analysed. All patients underwent SCS in a single referral centre between 2006 and 2018. The primary outcome was biochemical recurrence‐free survival (BRFS) according to the Phoenix definition (prostate‐specific antigen [PSA] nadir +2 ng/mL). The secondary outcomes were overall survival, BRFS defined as a PSA level of >0.5 ng/mL, metastasis‐free survival, androgen‐deprivation therapy (ADT)‐free survival, and functional outcomes. Complications were classified according to the Clavien–Dindo system. PSA was measured every 3–6 months postoperatively. Functional outcomes were scored as reported by patients at outpatient visits. Kaplan–Meier survival analysis and uni‐ and multivariable Cox regression were performed.

Results

The median (interquartile range) follow‐up was 36 (18–66) months. The BRFS after 5 and 8 years was 52% (95% confidence interval [CI] 43–62%) and 45% (95% CI 35–57%), respectively. At multivariable analysis PSA level at initial diagnosis, initial treatment, interval between primary treatment and SCS, age at SCS, and post‐SCS PSA nadir were significant factors for BRFS. The 5‐year ADT‐free survival was 70% (95% CI 62–79%). Clavien–Dindo Grade ≥III complications occurred in 1.2% (two/169) of patients. In all, 19% (29/156) of patients had new‐onset urinary incontinence defined as >1 pad/24 h and 92% (57/62) of patients had new‐onset erectile dysfunction. Persistent urinary fistula occurred in 6.5% (11/169) of patients.

Conclusions

The present study shows acceptable oncological outcomes of SCS considering the salvage character of the treatment. The occurrence of serious complications such as urinary incontinence and fistula should not be underestimated.
Multiparametric magnetic resonance imaging facilitates reclassification during active surveillance for prostate cancer
Authors: Fujihara Atsuko , Iwata Tsuyoshi , Shakir Aliasger , Tafuri Alessandro , Cacciamani Giovanni E. , Gill Karanvir , Ashrafi Akbar , Ukimura Osamu , Desai Mihir , Duddalwar Vinay , Stern Mariana S. , Aron Manju , Palmer Suzanne L. , Gill Inderbir S. , Abreu Andre Luis
Published: December 2020

Objective

To investigate the utility of multiparametric magnetic resonance imaging (mpMRI) in the reassessment and monitoring of patients on active surveillance (AS) for Grade Group (GG) 1 prostate cancer (PCa).

Patients and Methods

We identified, from our prospectively maintained institutional review board‐approved database, 181 consecutive men enrolled on AS for GG 1 PCa who underwent at least one surveillance mpMRI followed by MRI/prostate biopsy (PBx). A subset analysis was performed among 68 patients who underwent serial (at least two) mpMRI/PBx during AS. Pathological progression (PP) was defined as upgrade to GG ≥2 on follow up biopsy.

Results

Baseline MRI was performed in 34 patients (19%). At a median follow‐up of 2.2 years for the overall cohort, the PP was 12% (6/49) for Prostate Imaging Reporting and Data System (PI‐RADS) 1–2 lesions and 37% (48/129) for the PI‐RADS ≥3 lesions. The 2‐year PP‐free survival rate was 84%. Surveillance prostate‐specific antigen density (P < 0.001) and surveillance PI‐RADS ≥3 (P = 0.002) were independent predictors of PP on reassessment MRI/PBx. In the serial MRI cohort, the 2‐year PP‐free survival was 95% for the No‐MRI‐progression group vs 85% for the MRI‐progression group (P = 0.02). MRI progression was significantly higher in the PP (62%) than in the No‐PP (31%) group (P = 0.04). If serial MRI were used for PCa surveillance and biopsy were triggered based only on MRI progression, 63% of PBx might be postponed at the cost of missing 12% of GG ≥2 PCa in those with stable MRI. Conversely, this strategy would miss 38% of those with upgrading to GG ≥2 PCa on biopsy. Stable serial mpMRI correlates with no reclassification to GG ≥3 PCa during AS.

Conclusion

On surveillance mpMRI, PI‐RADS ≥3 was associated with increased risk of PCa reclassification. Surveillance biopsy based only on MRI progression may avoid a large number of biopsies at the cost of missing many PCa reclassifications.
Personalised three‐dimensional printed transparent kidney model for robot‐assisted partial nephrectomy in patients with complex renal tumours (R.E.N.A.L. nephrometry score ≥7): a prospective case‐matched study
Authors: Kwon Kim Jung , Ryu Hoyoung , Kim Myong , Kwon Eun‐Kyung , Lee Hakmin , Joon Park Sang , Byun Seok‐Soo
Published: December 2020

Objectives

To evaluate the effectiveness of a three‐dimensional (3D) printed transparent kidney model as a surgical navigator for robot‐assisted partial nephrectomy (RPN) in patients with complex renal tumours, defined by a R.E.N.A.L. (Radius, Exophytic/Endophytic, Nearness, Anterior/Posterior, Location) nephrometry score of ≥7.

Patients and Methods

A total of 80 patients who underwent RPN were included in the present prospective case‐matched study (case group [n = 40, application of 3D‐printed transparent kidney model during RPN] vs matching group [n = 40, routine protocol]). The RPNs were performed by a single experienced surgeon. The RPN procedure consisted of six steps: (i) preparation of the renal hilar vessel for clamping, (ii) tumour detection and dissection, (iii) robotic ultrasonography, (iv) tumour resection, (v) calyx repair and haemostasis, and (vi) renorrhaphy. The time for each step, console time, and warm ischaemia time were compared between the two groups as a surrogate marker for surgical effectiveness.

Results

Both groups were well‐balanced for all baseline characteristics. The use of the model reduced the console time by ~20% compared to the matched group (64.6 vs 78.5 min, P = 0.001). On multivariate logistic regression analysis, tumour radius (P < 0.001) and application of the model (P = 0.009) were identified as significant predictors of a console time of ≤70 min.

Conclusion

We established the usefulness of a personalised 3D‐printed transparent kidney model for more effective RPNs. Use of the 3D‐printed transparent kidney model reduced the operative time even for complex renal tumours and would be expected to broaden the indications for PN.
Value of tumour‐infiltrating immune cells in predicting response to intravesical BCG in patients with non‐muscle‐invasive bladder cancer: a systematic review and meta‐analysis
Authors: Kardoust Parizi Mehdi , Shariat Shahrokh F. , Margulis Vitaly , Mori Keiichiro , Lotan Yair
Published: December 2020

Objective

To investigate the predictive value of tumour‐infiltrating immune cells (TIICs) on oncological outcomes and response to BCG treatment in patients with non‐muscle‐invasive bladder cancer (NMIBC).

Materials and Methods

A systematic review and meta‐analysis was performed using PubMed, Scopus and the Cochrane Library in July 2020 to identify relevant studies according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement. The pooled recurrence‐free survival (RFS) rate was calculated using a fixed‐effect model.

Results

We retrieved 15 studies (including 791 patients) evaluating the effect of TIICs on oncological outcomes in patients with NMIBC treated with intravesical BCG. TIICs were reported to be a significant predictor of oncological outcomes and response to BCG treatment in 10 studies. Tumour‐associated macrophages were associated with worse RFS (pooled hazard ratio 2.30, 95% confidence interval 1.64–3.22).

Conclusions

Based on these data, TIICs are significant predictors of RFS and response to BCG treatment in patients with NMIBC; therefore, incorporation of TIICs into risk stratification models may help patients and physicians in the clinical decision‐making process in order to achieve the maximum possible benefit from BCG treatment.
The impact of racial residential segregation on prostate cancer diagnosis and treatment
Authors: Poulson Michael R. , Helrich Samuel A. , Kenzik Kelly M. , Dechert Tracey A. , Sachs Teviah E. , Katz Mark H.
Published: December 2020

Objectives

To examine the effects of racial residential segregation and structural racism on the diagnosis, treatment, and outcomes of patients with prostate cancer.

Patients and Methods

This retrospective cohort study examined men diagnosed with prostate cancer between 2005 and 2015. We collected data from Black and White men, aged ≥30 years, living within the 100 most populous counties participating in the Surveillance, Epidemiology, and End Results programme, a nationally representative dataset. The racial Index of Dissimilarity, a validated measure of segregation, was the primary exposure of interest. Outcomes of interest included advanced stage at diagnosis (Stage IV), surgery for localised disease (Stage I–II), and 10‐year overall and cancer‐specific survival. Multivariable Poisson regression analyses with robust error variance estimated the relative risk (RR) of advanced stage at diagnosis and surgery for localised disease at differing levels of segregation. Survival analysis was performed using competing hazards analysis.

Results

Multivariable models estimating stage at diagnosis showed that the disparities between Black and White men disappeared at low levels of segregation. Disparities in receiving surgery for localised disease persisted across all levels of segregation. In racially stratified analyses, segregation had no effect on stage at diagnosis or surgical resection for Black patients. White patients saw a 56% (RR 0.42, P < 0.001) reduced risk of presenting at advanced stage and 20% increased likelihood (RR 1.20, P < 0.001) of surgery for localised disease. Black patients in the lowest segregation areas had the lowest overall mortality, but the highest cancer‐specific mortality.

Conclusions

Our study provides evidence that residential segregation has a significant impact on Black–White disparities in prostate cancer, likely through improved outcomes for White patients and worse outcomes for Black patients in more segregated areas. These findings suggest that mitigating segregation and the downstream effects of socioeconomic factors could alleviate these disparities.
The obesity paradox: defining the impact of body mass index and diabetes mellitus for patients with non‐muscle‐invasive bladder cancer treated with bacillus Calmette–Guérin
Authors: Brooks Nathan A. , Kokorovic Andrea , Xiao Lianchen , Matulay Justin T. , Li Roger , Ranasinghe Weranja K.B. , Nagaraju Supriya , Shen Yu , Gao Jianjun , Navai Neema , Dinney Colin P.N. , Grossman H. Barton , Kamat Ashish M.
Published: December 2020

Objectives

To evaluate if the obesity paradox, wherein obesity portends worse overall prognosis for a disease but improved outcomes for patients receiving immunotherapy, exists for patients receiving bacillus Calmette–Guérin (BCG) in a contemporary cohort.

Patients and Methods

We performed an Institutional Review Board‐approved database review to identify patients with non‐muscle‐invasive bladder cancer (NMIBC) completing at least an induction course of BCG. Clinicopathological variables collected included: body mass index (BMI), medications, and diabetes mellitus (DM). Outcomes of interest included: recurrence‐free (RFS), progression‐free (PFS), cancer‐specific (CSS), and overall survival (OS). Univariate and multivariate modelling were used to evaluate the association between outcomes and clinical factors.

Results

A total of 579 patients (median follow‐up 4.6 years) received BCG induction for NMIBC; 90% had high‐grade disease (47.2% clinical stage T1). In all, 75.7% of patients were overweight or obese and 18% had DM. Aspirin, statins, metformin and β‐blockers were used in 34%, 42%, 11%, and 29% of patients, respectively. Overweight and obese patients had improved PFS, CSS and OS. DM was associated with worse RFS. Medications of interest had no association with outcomes.

Conclusion

Elevated BMI is associated with improved outcomes in patients with NMIBC treated with BCG immunotherapy. Patients with DM are at increased risk of recurrence. These findings support a potential obesity paradox in bladder cancer. Evaluation of the underlying mechanism and the role of global patient assessment, counselling, and risk factor modification are warranted.
Stress urinary incontinence in the mesh complication era: current Australian trends
Authors: Mathieson Rebecca , Kippen Rebecca , Manning Todd , Brennan Janelle
Published: December 2020

Objectives

To examine available data relating to the surgical management of stress urinary incontinence (SUI) in Australia before, during and after a well‐publicized Senate Inquiry into transvaginal mesh use and to consider outcomes in the context of global guideline changes.

Patients and Methods

The annual number of surgical procedures for the management of SUI by procedure type and age group for the years 2008/2009–2017/2018 was obtained from the Australian Government Department of Human Services database using Medicare Benefits Schedule item numbers. The data extracted were limited to women aged 25 years and older. These data were used to calculate age‐specific and age‐standardized rates, so as to accurately analyse trends in the usage of different procedures. Hospital Episode Statistics for mid‐urethral sling (MUS) insertions were obtained for England’s National Health Service from the Health and Social Care Information Centre for the years 2008/2009–2016/2017. These data were also used to calculate annual age‐standardized rates for comparison purposes.

Results

Rates declined for most SUI procedures over time (MUS, colposuspension, fascial slings) except for urethral bulking agents. The absolute number of MUSs implanted in 2008/2009 was 5729, which decreased to 3127 in the 2017/2018 financial year. Over the decade, the annual rate for MUS implantation per 100 000 population halved from 78 to 36. Over this same period, the rate of usage of bulking agents doubled, although represented a low volume of procedures (overall numbers increased from 304 to 698, representing an increase from four to eight procedures per 100 000 population). The age‐specific peak rate for MUS and Burch colposuspension changed over the decade from 55–64 years to 65–74 years, suggesting that women are deferring surgical treatment until later in life. Over the last decade, the total number of surgical procedures performed in Australia to treat SUI has decreased markedly from 6812 to 4279. This represents a decrease in the annual rate per 100 000 population from 93 to 49.

Conclusions

There are clear changes evident for SUI management in the past decade in Australia, including an overall decline in operative numbers, which correlate with international advisory notifications and local investigations. The results of the Australian Senate inquiry, including removal of single‐incision mini‐slings, greater availability of patient resources, and greater regulation of SUI procedures, will probably have ongoing effects. Surgeons need to ensure that sufficient training and patient education continue in order to maintain appropriate access to treatment of SUI in the future.
Round ligament suspending treatment in orthotopic ileal‐neobladder after radical cystectomy in women: a single‐centre prospective randomised trial
Authors: Zhou Xiaozhou , He Peng , Ji Huixiang , Wang Cong , Zhang Heng , Li Xuemei , Lang Lang , Zhou Zhansong , Wu Xiaojun , Chen Zhiwen
Published: December 2020

Objectives

To compare the occurrence of emptying dysfunction between surgical techniques for orthotopic neobladder suspended with round ligament (rONB) and the standard procedure (sONB).

Patients and Methods

A prospective randomised controlled trial was performed in a single centre of female patients undergoing creation of an ONB using rONB or sONB. Patients were followed for ≥24 months after ONB. The primary endpoints were significant post‐void residual urine volume (sPVR) and need for clean intermittent catheterisation (CIC) at 24 months postoperatively. The secondary endpoints included early and late complications, urodynamic profile, and ONB continence.

Results

Between January 2011 and October 2017, the trial enrolled 85 patients, of whom 82 were randomised. A total of 41 patients had a rONB and 41 a sONB. At 24 months, 17 of the 37 patients with a sONB and nine of the 39 patients with a rONB had a sPVR. The cumulative risk of a sPVR was significantly lower in the rONB group (23.1%) vs the sONB group (45.9%) (hazard ratio [HR] 0.43, 95% confidence interval [CI], 0.19–0.96; P = 0.040). In all, 15 of the 37 patients with a sONB and four of the 39 patients with a rONB needed CIC. The cumulative risk of requiring CIC was significantly lower in the rONB group (10.3%) vs the sONB group (40.5%) (HR 0.22, 95% CI 0.07–0.67; P = 0.008) at 24 months. Multivariable Cox regression analysis also showed that the rONB type was an independently protective factor for sPVR and CIC. The rates of early (0–90 days) and late complication (>90 days) were 54.1% and 13.5% in the sONB group, and 64.1% and 10.3% in the rONB group, respectively. There were no significant differences in complications, urodynamic profile or ONB continence. A major limitation is the small sample size at a single centre.

Conclusion

Posterior support with round ligament for an ONB significantly improved the emptying of the ONB and resulted in a reduced need for CIC. The surgical modification is a feasible and safe technique without additional complication‐related surgeries.
Implementation of frailty preoperative assessment to predict outcome in patients undergoing urological surgery: a systematic review and meta‐analysis
Authors: Aceto Paola , Bassi Pierfrancesco , Sollazzi Liliana , Racioppi Marco , Fortunato Giusy , Di Gianfrancesco Luca , Marusco Irene , Ragonese Mauro , Cataldo Andrea , Palermo Giuseppe
Published: December 2020

Background

A common limit of the widely used risk scores for preoperative assessment is the lack of information about aspects linked to frailty that may affect outcome, especially in the setting of elderly patients undergoing urological surgery. Frailty has recently been introduced as an additional characteristic to be assessed for better identifying patients at risk of negative outcomes.

Objective

To examine the evidence for recent advances in preoperative assessment in patients undergoing urological surgery focussing on the detrimental effect of frailty on outcome, including major (mPCs) and total postoperative complications (tPCs), discharge to a facility, and mortality. The secondary aim was to establish which cut‐off scores of the modified Frailty Index (mFI, 11 items) and/or simplified FI (sFI, five items) predicted PCs.

Methods

We searched PubMed, the Excerpta Medica database (EMBASE), Cochrane Library and clinicaltrial.gov from inception to 31 May 2020. Studies reporting relationships between the investigated outcomes and patients’ frailty were included. We estimated odds ratios (ORs) through a random effect model by using Revman 5.4.

Results

Frailty, assessed by different tools, was associated with a significantly higher rate of 30‐day (OR 1.73, 95% confidence interval [CI] 1.58–1.89) and 90‐day (OR 2.09, 95% CI 1.14–3.82) mPCs and 30‐day tPCs (OR 2.10, 95% CI 1.76–2.52). A mFI of ≥2 was associated with a higher rate of 30‐day mPCs (OR 1.79, 95% CI 1.69–1.89) and greater 30‐day mortality (OR 3.46, 95% CI 2.10–5.49). A pre‐planned post hoc analysis also revealed that a sFI of ≥3 was predictive of mPCs (OR 3.30, 95% CI 2.12–5.12).

Conclusions

Frailty assessment may help to predict PCs and mortality in patients undergoing major urological surgery. Either a mFi of ≥2 or sFI of ≥3 should be considered potential ‘red flags’ for preoperative risk assessment and decision‐making. There is not enough evidence to confirm the necessity to perform frailty assessment in minor urological surgery.
Tiny Drosophila makes giant strides in cancer research
Authors: Yamamura Ryodai , Ooshio Takako , Sonoshita Masahiro
Published: December 2020

Cancer burden has been increasing worldwide, making cancer the second leading cause of death in the world. Over the past decades, various experimental models have provided important insights into the nature of cancer. Among them, the fruit fly Drosophila as a whole‐animal toolkit has made a decisive contribution to our understanding of fundamental mechanisms of cancer development including loss of cell polarity. In recent years, scalable Drosophila platforms have proven useful also in developing anti‐cancer regimens that are effective not only in mammalian models but also in patients. Here, we review studies using Drosophila as a tool to advance cancer study by complementing other traditional research systems.
5HT3RA plus dexamethasone plus aprepitant for controlling delayed chemotherapy‐induced nausea and vomiting in colorectal cancer
Authors: Hayashi Toshinobu , Shimokawa Mototsugu , Matsuo Koichi , Nishimura Junichi , Iihara Hirotoshi , Nakano Takafumi , Egawa Takashi
Published: December 2020

Delayed chemotherapy‐induced nausea and vomiting (CINV) is not well controlled in colorectal cancer (CRC) patients undergoing oxaliplatin (L‐OHP)‐based chemotherapy. Whether neurokinin‐1 receptor antagonist addition to a first‐generation 5HT3 antagonist (1st 5‐HT3RA) and dexamethasone (DEX) is beneficial to these patients remains controversial. Furthermore, whether palonosetron (PALO) or aprepitant (APR) is more effective in controlling delayed CINV is unclear. We, therefore, investigated whether PALO+DEX or 1st 5‐HT3RA+DEX+APR was more effective in controlling delayed CINV, and the risk factors for delayed CINV, in CRC patients undergoing L‐OHP–based chemotherapy. Data were pooled from two prospective observational Japanese studies and a phase III trial to compare CINV incidence between the PALO + DEX (PALO) and 5‐HT3RA+DEX+APR (APR) groups by propensity score–matched analysis. CINV risk factors were identified using logistic regression models. The CINV incidence was higher in the PALO group than in the APR group. Logistic regression analysis revealed alcohol consumption, motion sickness, and the PALO+DEX regimen as independent risk factors for delayed nausea, and female sex and the PALO+DEX regimen as those for delayed vomiting. Compared with prophylactic PALO + DEX, 1st 5‐HT3RA+DEX+APR was more effective in controlling delayed CINV. Thus, CRC patients receiving L‐OHP–based chemotherapy should be treated with three antiemetics, including APR.
LPIN1 downregulation enhances anticancer activity of the novel HDAC/PI3K dual inhibitor FK‐A11
Authors: Imai Hiroo , Saijo Ken , Chikamatsu Sonoko , Kawamura Yoshifumi , Ishioka Chikashi
Published: December 2020

Phosphatidylinositol‐3 kinase (PI3K) inhibitor and histone deacetylase (HDAC) inhibitor have been developed as potential anticancer drugs. However, the cytotoxicity of PI3K inhibitor or HDAC inhibitor alone is relatively weak. We recently developed a novel HDAC/PI3K dual inhibitor FK‐A11 and confirmed its enhanced cytotoxicity when compared to that of PI3K inhibitor or HDAC inhibitor alone on several cancer cell lines. However, the in vivo antitumor activity of FK‐A11 was insufficient. We conducted high‐throughput RNA interfering screening and identified gene LPIN1 which enhances the cytotoxicity of FK‐A11. Downregulation of LPIN1 enhanced simultaneous inhibition of HDAC and PI3K by FK‐A11 and enhanced the cytotoxicity of FK‐A11. Propranolol, a beta‐adrenoreceptor which is also a LPIN1 inhibitor, enhanced the in vitro and in vivo cytotoxicity and antitumor effect of FK‐A11. These findings should help in the development of FK‐A11 as a novel HDAC/PI3K dual inhibitor.
Fungal sensitization and positive fungal culture from sputum in children with asthma are associated with reduced lung function and acute asthma attacks respectively
Authors: Welsh Kathryn G. , Holden Karl A. , Wardlaw Andrew J. , Satchwell Jack , Monteiro William , Pashley Catherine H. , Gaillard Erol A.
Published: December 2020

Background

Sensitization to thermotolerant fungi, including filamentous fungi and Candida albicans, is associated with poor lung function in adults with severe asthma. Data in children are lacking. Environmental exposure to fungi is linked with acute severe asthma attacks, but there are few studies reporting the presence of fungi in the airways during asthma attacks.

Methods

We investigated the association between fungal sensitization and/or positive fungal sputum culture and markers of asthma severity in children with chronic and acute asthma. Sensitization was determined using serum‐specific IgE and skin prick testing against a panel of five fungi. Fungal culture was focused towards detection of filamentous fungi from sputum samples.

Results

We obtained sensitization data and/or sputum from 175 children: 99 with chronic asthma, 39 with acute asthma and 37 controls. 34.1% of children with chronic asthma were sensitized to thermotolerant fungi compared with no children without asthma (p =< 0.001). These children had worse pre‐bronchodilator lung function compared with asthmatics without sensitization including a lower FEV1/FVC ratio (p < .05). The isolation rate of filamentous fungi from sputum was higher in children with acute compared with chronic asthma.

Conclusions

Fungal sensitization is a feature of children with chronic asthma. Children sensitized to thermotolerant fungi have worse lung function, require more courses of systemic corticosteroids and have greater limitation of activities due to asthma. Asthma attacks in children were associated with the presence of filamentous fungi positive sputum culture. Mechanistic studies are required to establish whether fungi contribute directly to the development of acute asthma.
MRGPRX2 activation in mast cells by neuromuscular blocking agents and other agonists: Modulation by sugammadex
Authors: Fernandopulle Nithya A. , Zhang Stephanie S. , Soeding Paul F. , Mackay Graham A.
Published: December 2020

Background

Neuromuscular‐blocking agents (NMBAs) can cause both IgE‐dependent and IgE‐independent anaphylactic reactions, with activation of the mast cell receptor MRGPRX2 being important to the latter. Sugammadex, a reversal agent for certain aminosteroid NMBAs, has been proposed as an antidote for these anaphylactic events with conflicting outcomes.

Objective

We further characterize the involvement of MRGPRX2 in NMBA‐induced mast cell activation and determine how this is influenced by sugammadex. We then apply these in vitro results to infer the possible utility of sugammadex in the acute management of non‐IgE‐dependent anaphylaxis.

Methods

The LAD2 human mast cell line and a MRGPRX2 knock‐down derivative were used to validate the involvement of MRGPRX2 and to test the effect of sugammadex on mast cell activation by NMBAs and other MRGPRX2 agonists.

Results

All MRGPRX2 agonists tested were shown to induce MRGPRX2‐dependent LAD2 mast cell calcium mobilization and cytokine release and all, apart from rocuronium, induced degranulation. Co‐treatment of mast cells with sugammadex and some MRGPRX2 agonists significantly reduced cell activation, but if sugammadex was administered a few minutes following stimulation, degranulation was not attenuated. However, addition of sugammadex up to 180 min following LAD2 MRGPRX2 stimulation, significantly reduced CCL2 mRNA and protein induction.

Conclusions and clinical relevance

We show that sugammadex, known to reverse muscle blockade by certain NMBAs, is also able to reduce MRGPRX2 activation by NMBAs and other, but not all, MRGPRX2 agonists. As sugammadex was ineffective in attenuating mast cell degranulation when added rapidly post MRGPRX2 activation, this suggests against the agent having efficacy in controlling acute symptoms of anaphylaxis to NMBAs caused by MRGPRX2 activation. Interestingly, however, sugammadex did impair MRGPRX2‐induced CCL2 release, suggesting that it may have some benefit in perhaps dampening less well‐defined adverse effects of MRGPRX2‐dependent anaphylaxis associated with the more slowly elaborated mast cell mediators.
Friends in Low‐Entropy Places: Orthographic Neighbor Effects on Visual Word Identification Differ Across Letter Positions
Authors: Luthra Sahil , You Heejo , Rueckl Jay G. , Magnuson James S.
Published: December 2020

Visual word recognition is facilitated by the presence of orthographic neighbors that mismatch the target word by a single letter substitution. However, researchers typically do not consider where neighbors mismatch the target. In light of evidence that some letter positions are more informative than others, we investigate whether the influence of orthographic neighbors differs across letter positions. To do so, we quantify the number of enemies at each letter position (how many neighbors mismatch the target word at that position). Analyses of reaction time data from a visual word naming task indicate that the influence of enemies differs across letter positions, with the negative impacts of enemies being most pronounced at letter positions where readers have low prior uncertainty about which letters they will encounter (i.e., positions with low entropy). To understand the computational mechanisms that give rise to such positional entropy effects, we introduce a new computational model, VOISeR (Visual Orthographic Input Serial Reader), which receives orthographic inputs in parallel and produces an over‐time sequence of phonemes as output. VOISeR produces a similar pattern of results as in the human data, suggesting that positional entropy effects may emerge even when letters are not sampled serially. Finally, we demonstrate that these effects also emerge in human subjects' data from a lexical decision task, illustrating the generalizability of positional entropy effects across visual word recognition paradigms. Taken together, such work suggests that research into orthographic neighbor effects in visual word recognition should also consider differences between letter positions.
Resilient and rapid recovery of native trout after removal of a non‐native trout
Authors: Budy Phaedra E. , Walsworth Timothy , Thiede Gary P. , Thompson Paul D. , McKell Matthew D. , Holden Paul B. , Chase Paul D. , Saunders W. Carl
Published: December 2020

While the importance of reducing impacts of non‐native species is increasingly recognized in conservation, the feasibility of such actions is highly dependent upon several key uncertainties including stage of invasion, size of the ecosystem being restored, and magnitude of the restoration activity. Here, we present results of a multi‐year, non‐native brown trout (Salmo trutta) removal and native Bonneville cutthroat trout (Oncorhynchus clarkii utah) response to this removal in a small tributary in the Intermountain West, United States. We monitored trout for 10 years prior to the onset of eradication efforts, which included 2 years of mechanical removal followed by 2 years of chemical treatment. Cutthroat trout were then seeded with low numbers of both eggs and juvenile trout. We monitored demographics and estimated population growth rates and carrying capacities for cutthroat trout from long‐term depletion estimate data, assuming logistic population growth. Following brown trout eradication and initial seeding efforts, cutthroat trout in this tributary have responded rapidly and have approached their estimated carrying capacity within 6 years. Population projections suggest a 95% probability that cutthroat trout will be at or above 90% of their carrying capacity within 10 years of the eradication of brown trout. Additionally, at least four age‐classes are present including adults large enough to satisfy angling demand. These results demonstrate native trout species have substantial capacity to rapidly recover following removal of invasive species in otherwise minimally altered habitats. While tributaries such as like this study location are likely limited in extent individually, collectively they may serve such as source populations for larger connected systems. In such cases, these source populations may provide additional conservation potential through biotic resistance.