bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ObjectivesTo 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 MethodsA 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.ResultsBoth 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.ConclusionWe 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

ObjectiveTo 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 MethodsA 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.ResultsWe 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).ConclusionsBased 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

ObjectivesTo examine the effects of racial residential segregation and structural racism on the diagnosis, treatment, and outcomes of patients with prostate cancer.Patients and MethodsThis 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.ResultsMultivariable 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.ConclusionsOur 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

ObjectivesTo 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 MethodsWe 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.ResultsA 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.ConclusionElevated 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

ObjectivesTo 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 MethodsThe 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.ResultsRates 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.ConclusionsThere 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

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

BackgroundA 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.ObjectiveTo 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.MethodsWe 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.ResultsFrailty, 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).ConclusionsFrailty 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

AbstractCancer 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

AbstractDelayed 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

AbstractPhosphatidylinositol‐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

AbstractBackgroundSensitization 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.MethodsWe 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.ResultsWe 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.ConclusionsFungal 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

AbstractBackgroundNeuromuscular‐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.ObjectiveWe 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.MethodsThe 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.ResultsAll 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 relevanceWe 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.