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Determining prostate cancer (PCa) aggressiveness and reclassification are critical events during the treatment of localized disease and for patients undergoing active surveillance (AS). Since T cells play major roles in cancer surveillance and elimination, we aimed to identify genetic biomarkers related to T cell cancer immune response which are predictive of aggressiveness and reclassification risks in localized PCa. The genotypes of 3,586 single nucleotide polymorphisms (SNPs) from T cell cancer immune response pathways were analyzed in 1762 patients with localized disease and 393 who elected AS. The aggressiveness of PCa was defined according to pathological Gleason score (GS) and D'Amico criteria. PCa reclassification was defined according to changes in GS or tumor characteristics during subsequent surveillance biopsies. Functional characterization and analysis of immune phenotypes were also performed. In the localized PCa cohort, seven SNPs were significantly associated with the risk of aggressive disease. In the AS cohort, another eight SNPs were identified as predictors for aggressiveness and reclassification. Rs1687016 of PSMB8 was the most significant predictor of reclassification. Cumulative analysis showed that a genetic score based on the identified SNPs could significantly predict risk of D'Amico high risk disease (P-trend = 2.4E-09), GS4 + 3 disease (P-trend = 1.3E-04), biochemical recurrence (P-trend = 0.01) and reclassification (P-trend = 0.01). In addition, the rs34309 variant was associated with functional somatic mutations in the PI3K/PTEN/AKT/MTOR pathway and tumor lymphocyte infiltration. Our study provides plausible evidence that genetic variations in T cell cancer immune response can influence risks of aggressiveness and reclassification in localized PCa, which may lead to additional biological insight into these outcomes. Abbreviations: PCa, prostate cancer; AS, active surveillance; GS, Gleason score; PSA, prostate specific antigen; TCGA, The Cancer Genome Atlas; SNP, single nucleotide polymorphisms; UFG, unfavorable genotype. [ABSTRACT FROM AUTHOR]

Tactile exchanges using the pectoral fin have been noted in a variety of dolphin species. In this study, bottlenose dolphins (Tursiops truncatus) at Zoo Duisburg in Germany were seen to exchange pectoral fin contact much like both wild and captive dolphins. The rate of overall contact (touches and rubs) was slightly larger among the Zoo Duisburg dolphins than for three other study sites, although relative rates for contact via rubs and touches by Zoo Duisburg dolphins appears similar to that of dolphins at the other study sites. Pectoral fin contact between Zoo Duisburg dolphins was more similar to that of dolphins at the Roatan Institute for Marine Sciences in that there was no difference in whether the dolphin was rubber or rubbee when initiating pectoral fin contact, although at all sites, including Zoo Duisburg, the rubber was more often the initiator of a pectoral fin contact. More similar to both wild groups, but not the other captive group of dolphins, Zoo Duisburg dolphins had a strong preference for the horizontal body posture when exchanging pectoral fin contacts. The most striking result is that all dolphins studied have a strong preference for body part contacted: when the rubbee is initiator, the top three body parts most contacted by all dolphins include the face, rostrum, and side. Similarly, when in the role of rubber initiator, the top most contacted and third most contacted body parts are identical at all four study sites. The exchange of contact via the pectoral fin seems to be a conserved action with respect to form and function across dolphin species regardless of the environment in which the dolphins reside. [ABSTRACT FROM AUTHOR]

Purpose of Review: Oligometastatic prostate cancer (OMPCa) is an intermediary state between localized and disseminated metastatic disease that has historically been treated with androgen deprivation therapy (ADT) and more recently with additional systemic therapies in combinations. However, cytoreductive control of the primary tumor may offer an opportunity to control the disease and enhance the response from systemic treatment. In this review, the use of local therapy to the prostate including cytoreductive prostatectomy (CRP), whole pelvis radiotherapy (RT), and focal therapies will be evaluated in the treatment of patients with newly diagnosed OMPCa., Recent Findings: Retrospective studies have demonstrated that some patients with OMPCa may indeed benefit from CRP. With preliminary trials demonstrating that CRP is safe and feasible, there are several phase II and III trials that are currently underway to investigate the role of CRP among patients with OMPCa. Results from several clinical trials have demonstrated that RT and ADT may benefit patients with OMPCa. Lastly, the evidence for focal and cryotherapy remains limited and further clinical trials are required., Summary: OMPCa is a unique disease state that may benefit from local therapy to the primary tumor. Further study is required to guide treatment selection and patient candidacy. Several trials specifically are awaited to better define the treatment options for patients., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cardiovascular diseases represent a hallmark characteristic in COPD, and endothelial dysfunction has been observed in these patients. Tetrahydrobiopterin (BH 4 ) is an essential cofactor for nitric oxide (NO) synthesis and a regulator of endothelial function. The goal of this study was to test the hypothesis that a single dose of BH 4 would improve endothelial function in patients with COPD via an increase in NO bioavailability., Methods: Seventeen patients with COPD completed a randomized, double-blind, placebo (PLC)-controlled, crossover trial with an acute dose of either BH 4 (Kuvan; BioMarin Pharmaceutical Inc) or PLC. Flow-mediated dilation (FMD), a bioassay of endothelial function, was completed prior to and 3 h following each treatment. Phospho- and total endothelial NO synthase (NOS3) protein was evaluated after incubating endothelial cells with plasma from the patients prior to and following treatment. Fifteen demographically matched control subjects were tested at baseline for case control comparisons., Results: Treatment with BH 4 significantly (P ≤ .004) increased FMD, improving endothelial function in patients compared to control values (P ≥ .327). BH 4 increased (P = .013) the ratio of phospho-NOS3 to total NOS3 protein. No changes in FMD (P ≥ .776) or the protein ratio (P = .536) were observed following PLC., Conclusions: An acute dose of BH 4 was able to improve endothelial function in patients with COPD to values similar to control subjects. The improvement in endothelial function was accompanied by an increase in NOS3 phosphorylation. BH 4 may represent a potential novel therapy to improve endothelial function and reduce cardiovascular disease risk in patients with COPD., Trial Registry: ClinicalTrials.gov; No.: NCT01398943; URL: www.clinicaltrials.gov., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Purpose: Symptomatic urinary tract infection is a complication of office based cystourethroscopy. Studies are mixed regarding the efficacy of antibiotic prophylaxis to prevent urinary tract infections. Our aim was to develop and evaluate an evidence-based protocol that reduces unnecessary antibiotic use while avoiding an increase in urinary tract infections., Materials and Methods: We created a clinic antibiogram based on all urology office visits performed during a 2-year period. Bacterial resistance rates, institutional risk related data and clinical guidelines were applied to create a protocol for antibiotic administration before cystourethroscopy. We then analyzed 1,245 consecutive patients without a renal transplant who underwent outpatient cystourethroscopy, including 610 after protocol initiation. Urinary tract infection rates and antibiotic use were analyzed for an association with the protocol change using the Fisher exact test., Results: Cultures had an overall 20% rate of resistance to fluoroquinolones, representing 40% of the cultures that grew Escherichia coli. Before the protocol change 602 of 635 patients (94.8%) received a preprocedural antibiotic compared to 426 of 610 (69.9%) after protocol initiation (p <0.01). A total of 19 patients (3.0%) had a symptomatic urinary tract infection prior to the protocol change while 16 (2.6%) had a urinary tract infection after the change (p = 0.69). Regarding resistance, fluoroquinolone resistant organisms grew in the cultures of 12 of 19 patients (63.2%) with a urinary tract infection before the protocol change compared to 5 of 16 (31.3%) with a urinary tract infection after the change. Recent antibiotic administration, hospitalization and chronic catheterization were associated with urinary tract infection in the entire cohort (all p ≤0.01)., Conclusions: A local antibiogram with infection related risk data effectively risk stratifies patients before cystourethroscopy, decreasing the use of antibiotics without increasing the rate of symptomatic urinary tract infection., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We sought to determine whether bladder neck size is associated with incontinence scores after robot-assisted laparoscopic radical prostatectomy., Materials and Methods: Consecutive eligible patients undergoing robot-assisted laparoscopic radical prostatectomy between July 19 and December 28, 2016 were enrolled in a prospective, longitudinal, observational cohort study. The primary outcome was patient reported urinary incontinence on the EPIC (Expanded Prostate Cancer Index Composite) scale 6 and 12 weeks postoperatively. The relationship between the EPIC score of urinary incontinence and bladder neck size was evaluated by multiple regression. Predicted EPIC scores for incontinence were displayed graphically after using restricted cubic splines to model bladder neck size., Results: A total of 107 patients were enrolled. The response rate was 98% and 87% at 6 and 12 weeks, respectively. Bladder neck size was not significantly associated with incontinence scores at 6 and 12 weeks. Comparing the 90th percentile for bladder neck size (18 mm) with the 10th percentile (7 mm) revealed no significant difference in adjusted EPIC scores for incontinence at 6 weeks (β coefficient 0.88, 95% CI -10.92-12.68, p = 0.88) or at 12 weeks (β coefficient 5.80, 95% CI -7.36-18.97, p = 0.39)., Conclusions: These findings question the merit of creating an extremely small bladder neck during robot-assisted laparoscopic radical prostatectomy. We contend that doing so increases the risk of positive margins at the bladder neck without facilitating early recovery of continence., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Symptomatic urinary tract infection (UTI) is a known complication of cystoscopy with ureteral stent removal. However, little is known about the incidence and risk factors for post-cystoscopy UTI in renal transplant recipients, who likely represent a high-risk cohort. Our aim was to determine the infection rate following cystoscopy with stent removal in this population and identify opportunities for care improvement., Methods: We performed a retrospective cohort study of office cystoscopies with stent removal in renal transplant recipients performed at a single institution from April 2012 through May 2014. Strict criteria were used to determine presence of symptomatic UTI within one month of the procedure. Fisher's exact tests were completed to examine associations between patient characteristics and post-transplant outcomes with UTI., Results: A total of 324 patients were included. Mean age was 50.0 (SD 13.1) years, and 187 (57.7%) patients were male. Within this group,165 (52.5%) patients received a pre-procedural oral fluoroquinolone antibiotic dose prior to the procedure. Nine patients had symptomatic UTIs (2.8%), of which three infections (33.3%) were due to quinolone-resistant organisms. Female sex ( P =0.04), but no other patient or post-operative characteristic was associated with symptomatic UTI, including the use of peri-procedural antibiotics., Conclusions: The incidence of symptomatic UTI after cystoscopy with ureteral stent removal in renal transplant recipients is less than three percent and comparable to post-cystoscopy UTI risk in the general population. Female sex is associated with symptomatic UTI. Further investigation is needed to identify groups most at risk for UTI and other complications.

Background: Aspirin at 325 mg twice daily is now included as a nationally approved venous thromboembolism (VTE) prophylaxis protocol for low-risk total knee arthroplasty (TKA) patients. The purpose of this study is to examine whether there is a difference in deep vein thrombosis (DVT) occurrence after a limited tourniquet TKA using aspirin-based prophylaxis with or without extended use of mechanical compression device (MCD) therapy., Methods: One hundred limited tourniquet TKA patients, whose DVT risk was managed with aspirin 325 mg twice daily for 3 weeks, were randomized to either using an MCD during hospitalization only or extended use at home up to 6 weeks postoperatively. Lower extremity duplex venous ultrasonography (LEDVU) was completed on the second postoperative day, 14 days postoperatively, and at 3 months postoperatively to confirm the absence of DVT after treatment., Results: The DVT rate for the postdischarge MCD therapy group was 0% and 23.1% for the inpatient MCD group (P < .001). All DVTs resolved by 3 months postoperatively. Patient satisfaction was 9.56 (±0.82) for postdischarge MCD patients vs 8.50 (±1.46) for inpatient MCD patients (P < .001)., Conclusion: Limited tourniquet TKA patients who were mobilized early, managed with aspirin for 3 weeks postoperatively, and on MCD therapy for up to 6 weeks postoperatively experienced superior DVT prophylaxis than patients receiving MCD therapy only as an inpatient (P < .05). The 0% incidence of nonsymptomatic DVTs prevented by aspirin and extended-use MCD further validates this type of prophylaxis in low DVT risk TKA patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: The diagnosis and subsequent management of bladder cancer often involves transurethral resection of bladder tumor (TURBT). Risks of TURBT include perioperative complications such as bleeding, pain and perforation. We aimed to determine TURBT complication rates and risk factors in a contemporary series., Materials and Methods: From 2002 to 2011, 505 patients underwent TURBT either for suspected bladder cancer or during follow up at a single institution. Baseline patient characteristics and complications within 2 weeks of surgery were extracted from the electronic medical record for all TURBTs. Patient and tumor characteristics were evaluated for associations with complication using univariate analysis. A multivariable logistic regression was fit to further examine associations between TURBT related characteristics and complication., Results: A total of 910 TURBTs were performed on 505 patients. Overall complication rate was 8.1%. The most common complications were pain or spasm (3.0%), retention (2.8%), and infection (2.1%), and 0.5% of TURBTs had perforation. Over 85% of complications were Clavien-Dindo grade I or II. Forty-three patients had a complication after their first TURBT, while 25 had complications after subsequent TURBTs. Prior complication and single tumor, but not other patient or tumor-related characteristics, were associated with complication. Only prior complication (p < 0.01) was associated with subsequent complication after TURBT on multivariable analysis., Conclusions: Complication rate after TURBT is 8.1% and complications are generally not severe in nature. Prior short term complication is likely associated with subsequent complication. Further studies are needed to validate these results and determine patient groups most at risk for intraoperative and post TURBT complications.