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The presence of detrusor muscle is essential for accurate staging of T1 cancers. Detrusor muscle presence can be a quality indicator of transurethral resection of bladder tumor for nonmuscle invasive bladder cancer. We hypothesized that increasing surgeon awareness of personal and institutional detrusor muscle sampling rates could improve resection quality and long-term oncologic outcomes.A retrospective review of transurethral resections of bladder tumor from 1/2006 to 2/2018 was performed. The presence of detrusor muscle in the pathology report and transurethral resection specimen were extracted from records. Individual surgeon scorecards were created and distributed. Rates of detrusor muscle sampling were compared prior to and 12 months after distribution. Chart review was done to compare 3-year recurrence and progression outcomes before and after distribution of scorecards.The rate of detrusor muscle sampling increased from 36% (1,250/3,488) to 54% (202/373) (p=0.001) in the 12 months after scorecard distribution, ie from 30% (448/1,500) to 55% (91/165) (p0.001) in Ta tumors and from 47% (183/390) to 72% (42/58) (p0.001) in T1 tumors. Pathological reporting of muscle also improved for all samples (73%, 2,530/3,488 to 90%, 334/373, p0.001), Ta (75%, 1,127/1,500 to 94%, 155/165, p0.001) and T1 (93%, 362/390 to 100%, 58/58, p=0.04). On multivariate Cox regression analysis, the surgeon scorecard was associated with decreased 3-year risk of recurrence (HR 0.63, 95% CI 0.40-0.99).Creation and distribution of individual surgeon scorecards improved detrusor muscle sampling on transurethral resection and was associated with decreased risk of disease recurrence. Quality evaluation of transurethral resection of bladder tumor may contribute to improved outcomes of patients with nonmuscle invasive bladder cancer.

Purpose Bladder cancer is initially diagnosed and staged with a transurethral resection of bladder tumor (TURBT). Patient survival is dependent on appropriate sampling of layers of the bladder, but pathology reports are dictated as free text, making large-scale data extraction for quality improvement challenging. We sought to automate extraction of stage, grade, and quality information from TURBT pathology reports using natural language processing (NLP). Methods Patients undergoing TURBT were retrospectively identified using the Northwestern Enterprise Data Warehouse. An NLP algorithm was then created to extract information from free-text pathology reports and was iteratively improved using a training set of manually reviewed TURBTs. NLP accuracy was then validated using another set of manually reviewed TURBTs, and reliability was calculated using Cohen’s κ. Results Of 3,042 TURBTs identified from 2006 to 2016, 39% were classified as benign, 35% as Ta, 11% as T1, 4% as T2, and 10% as isolated carcinoma in situ. Of 500 randomly selected manually reviewed TURBTs, NLP correctly staged 88% of specimens (κ = 0.82; 95% CI, 0.78 to 0.86). Of 272 manually reviewed T1 tumors, NLP correctly categorized grade in 100% of tumors (κ = 1), correctly categorized if muscularis propria was reported by the pathologist in 98% of tumors (κ = 0.81; 95% CI, 0.62 to 0.99), and correctly categorized if muscularis propria was present or absent in the resection specimen in 82% of tumors (κ = 0.62; 95% CI, 0.55 to 0.73). Discrepancy analysis revealed pathologist notes and deeper resection specimens as frequent reasons for NLP misclassifications. Conclusion We developed an NLP algorithm that demonstrates a high degree of reliability in extracting stage, grade, and presence of muscularis propria from TURBT pathology reports. Future iterations can continue to improve performance, but automated extraction of oncologic information is promising in improving quality and assisting physicians in delivery of care.

Due to their ubiquity, management of parasites is a common and important factor for profitable production of poultry. Heterakis gallinarum, the cecal nematode, is the most common nematode parasite of poultry. While typically causing no pathology on its own, H. gallinarum is the vector of Histomonas meleagridis, a protozoan parasite that causes blackhead disease. Histomonas meleagridis is highly pathogenic in turkeys, potentially causing high mortality. In contrast, disease caused by H. meleagridis is much less severe in chickens, where it primarily reduces productivity without manifestations of clinical disease. There are no approved treatments for H. meleagridis, making control reliant on control of the helminth vector through the use of fenbendazole (FBZ) the only drug labeled for treatment of H. gallinarum in the United States We were contacted by an industry veterinarian regarding health-related concerns in a broiler-breeder house due to histomoniasis, despite frequent anthelmintic treatments. Since we had recently diagnosed resistance to FBZ in Ascaridia dissimilis, a closely related nematode of turkeys, we were interested to determine if H. gallinarum had also evolved resistance to FBZ. Heterakis gallinarum eggs were isolated from litter collected from the house and used to infect 108 chickens. Treatment groups included a non-treated control, a label-dose and a 2X-label dose of FBZ, with 36 birds per group divided into two replicate pens of 18 birds each. Birds were placed at 1-day post hatch, and at 3 weeks of age were infected with 150 embryonated eggs via oral gavage. Two weeks post infection, treated birds were administered a minimum of either a label- or 2X label-dose of FBZ in water for 5 days (SafeGuard® Aquasol, 1mg/kg BW). To ensure that all birds consumed the full intended dose at a minimum, the dosage was calculated using 1.25 times the average body weight. One-week post treatment, birds were euthanized, ceca removed, and parasites enumerated. Efficacy was calculated by comparing the total numbers of worms recovered from each treatment group to the numbers recovered in the non-treated control group. There were no significant differences in worm numbers recovered from any of the three groups (p-value=0.81). There also was no efficacy benefit to treatment with a 2X dose; H. gallinarum worm counts were reduced by 42.7% and 41.4%, for the label and 2X dosages, respectively. These data provide strong evidence that H. gallinarum has developed resistance to FBZ. Consequently, in houses infected with FBZ-resistant H. gallinarum, H. meleagridis will be able to cycle through the birds in an unrestricted manner. Further investigation is needed to determine the prevalence of resistance in H. gallinarum on chicken farms, but it is clear this has the potential to have a large-scale economic impact on the poultry industry. These data when viewed together with our recent findings of FBZ resistance in A. dissimilis, suggest that drug resistance in ascarid nematodes may be an important emerging problem on poultry operations.

The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we performed a large integrative multi-omics analysis of patients diagnosed with NMIBC (n=834). Transcriptomic analysis identified four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provided independent prognostic value beyond established prognostic clinicopathological parameters. High chromosomal instability, p53-pathway disruption and APOBEC-related mutations were significantly associated with transcriptomic class 2a and poor outcome. RNA-derived immune cell infiltration was associated with chromosomally unstable tumors and enriched in class 2b. Spatial proteomics analysis confirmed the higher infiltration of class 2b tumors and demonstrated an association between higher immune cell infiltration and lower recurrence rates. Finally, a single-sample classification tool was built and the independent prognostic value of the transcriptomic classes was documented in 1306 validation samples. The classifier provides a framework for novel biomarker discovery and for optimizing treatment and surveillance in next-generation clinical trials.

Introduction:We evaluated the timing, frequency and antibiotic sensitivity of post-radical cystectomy urinary tract infections to guide an infection reduction initiative.Methods:A combined ...

Stage T1 bladder cancers have the highest progression and recurrence rates of all non-muscle-invasive bladder cancers (NMIBCs). Most T1 cancers are treated with bacillus Calmette-Guerin (BCG), but many will progress or recur, and some T1 patients will die from bladder cancer. Particularly aggressive tumors could be treated with early cystectomy. To better understand the molecular heterogeneity of T1 cancers, we performed transcriptome profiling and unsupervised clustering, and identified five consensus subtypes of T1 tumors treated with repeat transurethral resection (reTUR) and induction and maintenance BCG. The T1-LumGU subtype was associated with carcinoma in situ (CIS; six/13, 46% of all CIS), had high E2F1 and EZH2 expression, and was enriched in E2F target and G2M checkpoint hallmarks. The T1-Inflam subtype was inflamed and infiltrated with immune cells. While most T1 tumors were classified as luminal papillary, the T1-TLum subtype had the highest median luminal papillary score and FGFR3 expression, no recurrence events, and the fewest copy number gains. T1-Myc and T1-Early subtypes had the most recurrences (14/30 within 24 mo), the highest median MYC expression, and, when combined, had significantly worse recurrence-free survival than the other three subtypes. T1-Early had five (38%) recurrences within the first 6 mo of BCG, and repressed IFN-α and IFN-γ hallmarks and inflammation. We developed a single-patient T1 classifier and validated our subtype biology in a second cohort of T1 tumors. Future research will be necessary to validate the proposed T1 subtypes and to determine if therapies can be individualized for each subtype. PATIENT SUMMARY: We identified and characterized expression subtypes of high-grade stage T1 bladder cancer that are biologically heterogeneous and have variable responses to bacillus Calmette-Guerin treatment. We validated the subtypes and describe a single-patient classifier.

Stage T1 bladder cancers invade the lamina propria of the bladder and, despite sharing many of the genetic features of muscle-invasive bladder cancers, are classified as non-muscle-invasive or ‘superficial’ tumours. Yet, patients with T1 bladder cancer have an overall mortality of 33% and a cancer-specific mortality of 14% at three years after diagnosis, suggesting that these patients have a high risk of progression and, accordingly, require meticulous surgery, endoscopic surveillance and clinical decision-making. We hypothesize that the variability in the outcomes of patients with T1 bladder cancer is a result of both tumour heterogeneity and pathological staging, as well as inconsistencies in risk stratification, endoscopic resection and schedules of delivery of BCG. Owing to limitations in clinical staging, patients with T1 bladder cancer are at risk of both undertreatment with persistent use of BCG despite recurrence, and overtreatment with early cystectomy. Understanding the molecular features of T1 bladder cancers and how they respond to BCG therapy could improve biomarkers for risk stratification to align therapy with biological risk. Patients with stage T1 bladder cancer require meticulous management owing to their high-risk of recurrence, progression and death. Here, Jordan and Meeks describe the natural history, diagnosis, and treatment of T1 bladder cancer, highlighting key challenges and areas of future investigation.

Background: Radical cystectomy (RC) is a morbid procedure with frequent complications that may benefit from implementation of an enhanced recovery after surgery (ERAS) protocol. Objective: To examine the benefits of a multimodal analgesic plan that uses continuous transversus abdominis plane (TAP) blockade as part of an ERAS protocol after RC. Methods: A retrospective comparison of consecutive patients undergoing RC over a 4-year period was conducted. Patients were designated as having surgery either before or after implementation of an ERAS protocol. A major component of the ERAS protocol was a multi-modal analgesia plan with TAP blockade. Patient demographics, comorbidities, operative details, and outcomes, including days to flatus, bowel movement (BM), narcotic usage, and length of stay (LOS) were compared. Results: In total, 171 patients were included: 100 pre-ERAS and 71 ERAS. There were no differences in age, smoking status, operative approach, or diversion type. The patients in the ERAS cohort were less likely to be male, had a higher median BMI, and more likely to have received neoadjuvant chemotherapy. Total and early postoperative narcotic use were lower in the ERAS cohort: 89 vs. 336 mg (p

To evaluate the rate of venous thromboembolism (VTE) after nephrectomy with specific focus on event timing and location (before or after hospital discharge) in order to identify modifiable risk factors and establish benchmarks for preventive interventions. Using the ACS-NSQIP database, we identified patients undergoing nephrectomy from 2006 to 2012. Patients were analyzed in two cohorts: collectively and by surgical approach [open vs. lap/robotic (MIS)]. Rates of deep vein thrombosis (DVT) and pulmonary embolus (PE) were assessed and time to each event was established in relation to discharge status. Logistic regression analysis was performed to assess association between preoperative risk factors, surgical variables, and VTE. In total, 13,208 patients met inclusion criteria. The overall rate of VTE was 1.2% (PE = 0.5% and DVT = 0.8, 0.1% DVT and PE). Using regression analysis, diabetes, dependent functional status, and longer operative time were associated with higher odds of DVT. For PE, dyspnea, disseminated cancer, and longer operative time were significant associations. The rate of VTE was higher in open surgery compared to MIS (2 vs. 0.8%, p

This is a case of emphysematous cystitis with a rare complication of bladder rupture requiring surgical intervention in a diabetic man who presented with urinary retention and abdominal pain, with a large amount of intraperitoneal free air on computed tomography scan. Keywords: Emphysematous cystitis, Bladder rupture, Pneumoperitoneum

Avian respiratory disease causes significant economic losses in commercial poultry. Because of the need to protect long-lived poultry against respiratory tract pathogens from an early age, vaccination programs for pullets typically involve serial administration of a variety of vaccines, including infectious bronchitis virus (IBV), Newcastle disease virus (NDV), and infectious laryngotracheitis virus (ILTV). Often the interval between vaccinations is only a matter of weeks, yet it is unknown whether the development of immunity and protection against challenge when vaccines are given in short succession occurs in these birds, something known as viral interference. Our objective was to determine whether serially administered, live attenuated vaccines against IBV, NDV, and ILTV influence the development and longevity of immunity and protection against challenge in long-lived birds. Based on a typical pullet vaccination program, specific-pathogen-free white leghorns were administered multiple live attenuated vaccines against IBV, NDV, and ILTV until 16 weeks of age (WOA), after which certain groups were challenged with IBV, NDV, or ILTV at 20, 24, 28, 32, and 36 WOA. Five days post-challenge, viral load, clinical signs, ciliostasis, tracheal histopathology, and antibody titers in serum and tears were evaluated. We demonstrate that pullets serially administered live attenuated vaccines against IBV, NDV, and ILTV were protected against homologous challenge with IBV, NDV, or ILTV for at least 36 weeks, and conclude that the interval between vaccinations used in this study (at least 2 weeks) did not interfere with protection. This information is important because it shows that a typical pullet vaccination program consisting of serially administered live attenuated vaccines against multiple respiratory pathogens can result in the development of protective immunity against each disease agent.

Bladder reconstructions are commonly performed in patients with neurogenic bladders with a high rate of complications. We seek to help guide the evaluation and management of these complications by reviewing the available data. Augmentation cystoplasty and concomitant procedures such as continent catheterizable channels, bladder neck closure, and bladder neck sling can provide long-term solutions for patients with poorly compliant, high-pressure bladders or refractory detrusor overactivity. While these techniques improve symptoms and protect against upper tract deterioration, patients are exposed to new risks including bladder perforation, increased malignancy rates, urolithiasis, surgical failures, and persistent symptoms. The overall rate of reoperation is high. Evaluation with urodynamics and endoscopy, when indicated, remain critical tools to protect this patient population. Use of clean intermittent catheterization has helped popularize bladder reconstructive surgery, but a strict regimen is required to minimize postoperative risks in the long term. Additionally, various surgical techniques can be utilized to manage complications after bladder reconstruction, and concurrent use of anticholinergics and onabotulinum toxin injections can further mitigate these reconstructive failures. Bladder reconstruction can provide excellent long-term solutions, but patients are at a high risk of long-term complications. Appropriate patient counseling, close follow-up, and timely evaluation are crucial in managing the long-term complications of bladder reconstruction surgery.

studies in our laboratory showed that the Arkansas-Delmarva Poultry Industry (Ark-DPI) vaccine given to 1-day-old chickens by hatchery spray cabinet replicated poorly and failed to adequately protect broilers against homologous virus challenge, whereas the same vaccine given by eye-drop did replicate and the birds were protected following homologous virus challenge. To determine if mechanical damage following spray application plays a role in failure of the Ark-DPI vaccine, we examined the morphology of three Ark-DPI vaccines from different manufacturers using an electron microscope and included a Massachusetts (Mass) vaccine as control. One of the Ark-DPI vaccines (vaccine A) and the Mass vaccine had significantly (P0.005) fewer spikes than the other two Ark-DPI vaccines. We also found that the Ark-DPI and Mass vaccines had significantly (P0.005) fewer spike proteins per virus particle when compared to their respective challenge viruses. This observation is interesting and may provide some insight into the mechanism behind infectious bronchitis virus attenuation. No obvious differences were observed in virus morphology and no consistent trend in the number of spikes per virion was found in before- and after-spray samples. We also determined the vaccine titer before and after spray in embryonated eggs and found that both Ark-DPI and Mass vaccines had a similar drop in titer, 0.40 logi and 0.310 logi, respec10ively. Based on these data, it appears that mechanical damage to the Ark-DPI vaccine is not occurring when delivered by a hatchery spray cabinet, suggesting that some other factor is contributing to the failure of that vaccine when given by that method.

The Arkansas Delmarva Poultry Industry (ArkDPI) infectious bronchitis virus (IBV) vaccine is effective when administered by eye drop, where the vaccine virus is able to infect and replicate well in birds and is able to induce protection against homologous challenge. However, accumulating evidence indicates that the ArkDPI vaccine is ineffective when applied by hatchery spray cabinet using the same manufacturer-recommended dose per bird. For this study, we aimed to determine the minimum infectious dose for the spray-administered ArkDPI vaccine, which we designate as the dose that achieves the same level of infection and replication as the eye drop-administered ArkDPI vaccine. To this end, we used increasing doses of commercial ArkDPI vaccine to vaccinate 100 commercial broiler chicks at day of hatch, using a commercial hatchery spray cabinet. The choanal cleft of each bird was swabbed at 7 and 10 days postvaccination, and real-time reverse-transcriptase PCR was performed. We observed that the level of infection and replication with spray vaccination matches with that of eye drop vaccination when chicks received 100 times the standard dose for the commercial ArkDPI vaccine. We further examined the S1 spike gene sequence from a subset of reisolated ArkDPI vaccine virus samples and observed that certain nucleotide changes arise in vaccine viruses reisolated from chicks, as previously reported. This suggests that the ArkDPI vaccine has a certain virus subpopulation that, while successful at infecting and replicating in chicks, represents only a minor virus subpopulation in the original vaccine. Thus, the minimum infectious dose for the ArkDPI vaccine using a hatchery spray cabinet appears to be dependent on the amount of this minor subpopulation reaching the chicks.

Infectious bronchitis virus (IBV) is a significant respiratory pathogen of commercial poultry that causes millions of dollars in lost revenue worldwide each year. Even though the poultry industry extensively vaccinates against IBV, emergence of new serotypes and variants continually occur, making control of the disease difficult. Current mass application strategies for IBV vaccines are inefficient and frequently result in vaccination failures. Novel vaccine technology development has been slow, and is hindered by the constraints of large-scale poultry production. Further complicating the situation is the lack of knowledge of IBV protein and host cell interactions, making targeted vaccine intervention strategies near impossible. Taken together, it is easy to see why this disease remains significant in poultry production. This review outlines the current situation as it relates to IBV control, including vaccination, vaccines, and development of immunity, and recent developments in vaccine technology that may provide better protection in the future.

Purpose To evaluate the rate of venous thromboembolism (VTE) after nephrectomy with specific focus on event timing and location (before or after hospital discharge) in order to identify modifiable risk factors and establish benchmarks for preventive interventions.

We report the modulation of the absorbance of a flavin push-pull derivative through specific recognition by a complementary diamidopyridine (DAP), shifting the flavin intramolecular charge transfer band by approximately 30 nm.