Quantifying the Impact of Cancer on the Viscoelastic Properties of the Prostate Gland using a Quasi-Linear Viscoelastic Model.

Pathological disorders can alter the mechanical properties of biological tissues, and studying such changes can help to better understand the disease progression. The prostate gland is no exception, as previous studies have shown that cancer can affect its mechanical properties. However, most of these studies have focused on the elastic properties of the tissue and have overlooked the impact of cancer on its viscous response. To address this gap, we used a quasi-linear viscoelastic model to investigate the impact of cancer on both the elastic and viscous characteristics of the prostate gland. By comparing the viscoelastic properties of segments influenced by cancer and those unaffected by cancer in 49 fresh prostates, removed within two hours after prostatectomy surgery, we were able to determine the influence of cancer grade and tumor volume on the tissue. Our findings suggest that tumor volume significantly affects both the elastic modulus and viscosity of the prostate (p-value less than 2%). Specifically, we showed that cancer increases Young's modulus and shear relaxation modulus by 20%. These results have implications for using mechanical properties of the prostate as a potential biomarker for cancer. However, developing an in vivo apparatus to measure these properties remains a challenge that needs to be addressed in future research. STATEMENT OF SIGNIFICANCE: This study is the first to explore how cancer impacts the mechanical properties of prostate tissues using a quasi-linear viscoelastic model. We examined 49 fresh prostate samples collected immediately after surgery and correlated their properties with cancer presence identified in pathology reports. Our results demonstrate a 20% change in the viscoelastic properties of the prostate due to cancer. We initially validated our approach using tissue-mimicking phantoms and then applied it to differentiate between cancerous and normal prostate tissues. These findings offer potential for early cancer detection by assessing these properties. However, conducting these tests in vivo remains a challenge for future research.

Stimulated Raman histology as a method to determine the adequacy of renal mass biopsy and identify malignant subtypes of renal cell carcinoma.

INTRODUCTION: Renal tumor biopsy requires adequate tissue sampling to aid in the investigation of small renal masses. In some centers the contemporary nondiagnostic renal mass biopsy rate may be as high as 22% and may be as high as 42% in challenging cases. Stimulated Raman Histology (SRH) is a novel microscopic technique which has created the possibility for rapid, label-free, high-resolution images of unprocessed tissue which may be viewed on standard radiology viewing platforms. The application of SRH to renal biopsy may provide the benefits of routine pathologic evaluation during the procedure, thereby reducing nondiagnostic results. We conducted a pilot feasibility study, to assess if renal cell carcinoma (RCC) subtypes may be imaged and to see if high-quality hematoxylin and eosin (H&E) could subsequently be generated. METHODS/MATERIALS: An 18-gauge core needle biopsy was taken from a series of 25 ex vivo radical or partial nephrectomy specimens. Histologic images of the fresh, unstained biopsy samples were obtained using a SRH microscope using 2 Raman shifts: 2,845 cm-1 and 2,930 cm-1. The cores were then processed as per routine pathologic protocols. The SRH images and hematoxylin and eosin (H&E) slides were then viewed by a genitourinary pathologist. RESULTS: The SRH microscope took 8 to 11 minutes to produce high-quality images of the renal biopsies. Total of 25 renal tumors including 1 oncocytoma, 3 chromophobe RCC, 16 clear cells RCC, 4 papillary RCC, and 1 medullary RCC were included. All renal tumor subtypes were captured, and the SRH images were easily differentiated from adjacent normal renal parenchyma. High quality H&E slides were produced from each of the renal biopsies after SRH was completed. Immunostains were performed on selected cases and the staining was not affected by the SRH image process. CONCLUSION: SRH produces high quality images of all renal cell subtypes that can be rapidly produced and easily interpreted to determine renal mass biopsy adequacy, and on occasion, may allow renal tumor subtype identification. Renal biopsies remained available to produce high quality H&E slides and immunostains for confirmation of diagnosis. Procedural application has promise to decrease the known rate of renal mass nondiagnostic biopsies, and application of convolutional neural network methodology may further improve diagnostic capability and increase utilization of renal mass biopsy among urologists.

The "Ins and Outs" of Prostate Specific Membrane Antigen (PSMA) as Specific Target in Prostate Cancer Therapy.

Prostate-specific membrane antigen (PSMA) is expressed in epithelial cells of the prostate gland and is strongly upregulated in prostatic adenocarcinoma, with elevated expression correlating with metastasis, progression, and androgen independence. Because of its specificity, PSMA is a major target of prostate cancer therapy; however, detectable levels of PSMA are also found in other tissues, especially in salivary glands and kidney, generating bystander damage of these tissues. Antibody target therapy has been used with relative success in reducing tumor growth and prostate specific antigen (PSA) levels. However, since antibodies are highly stable in plasma, they have prolonged time in circulation and accumulate in organs with an affinity for antibodies such as bone marrow. For that reason, a second generation of PSMA targeted therapeutic agents has been developed. Small molecules and minibodies have had promising clinical trial results, but concerns about their specificity had arisen with side effects due to accumulation in salivary glands and kidneys. Herein we study the specificity of small molecules and minibodies that are currently being clinically tested. We observed a high affinity of these molecules for PSMA in prostate, kidney and salivary gland, suggesting that their effect is not prostate specific. The search for specific prostate target agents must continue so as to optimally treat patients with prostate cancer, while minimizing deleterious effects in other PSMA expressing tissues.

Detection and resection of carcinoma in situ of the bladder: Implications for clinical trial design.

INTRODUCTION: The path to approval of novel therapeutics for patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) requires demonstration of efficacy in eradicating carcinoma in situ (CIS), as determined by cytology, white light cystoscopy and only sometimes mandatory re-biopsy. This paradigm is based on the premise that CIS, in contrast to papillary tumors, cannot be completely resected. We aimed to determine the accuracy of CIS by standard means and the rate at which CIS may be eradicated by transurethral bladder tumor resection (TURBT). METHODS: We performed a retrospective analysis of consecutive patients who underwent radical cystectomy (RC) for high risk NMIBC or muscle invasive bladder cancer (MIBC) between 2005 and 2019 in a tertiary academic center. The concordance in the presence of CIS in matched TURBT and RC samples was calculated. RESULTS: Complete pathologic information was available for 816 patients with urothelial carcinoma. CIS was detected at TURBT in 354 (43.4%) patients (64.0% NMIBC, 32.3% MIBC) and at RC in 436 (53.4%) patients (64.7% NMIBC, 47.4% MIBC). CIS was missed by TURBT in 199 (45.6%) of those cases (NMIBC 25.4%, MIBC 60.6%). CIS detected on TURBT was not found in the RC specimen in 33.1% (117/354) of cases. Lack of prospective bladder mapping and central pathology review are limitations. CONCLUSION: Our results suggest that TURBT is inaccurate in detecting CIS. The absence of CIS in the RC specimen after detection in the matched TURBT specimen suggests that CIS may be completely resected by TURBT in a proportion of patients. These factors need to be considered in the design of clinical trials in patients with NMIBC. The use of random biopsies or enhanced cystoscopy could improve the accuracy of CIS detection, but the former is associated with patient morbidity and randomization would alleviate concern about these variables impacting clinical trial outcomes.

Is the Unequal COVID-19 Burden in Canada Due to Unequal Levels of Citizen Discipline across Provinces?

The unequal burden of the coronavirus disease 2019 (COVID-19) crisis (e.g., in terms of infection and death rates) across Canadian provinces is important and puzzling. Some have speculated that differences in levels of citizen compliance with public health preventive measures are central to understanding cross-provincial differences in pandemic-related health outcomes. However, no systematic empirical test of this hypothesis has been conducted. In this research, we make use of an exceptionally large dataset that includes 23 survey waves (N = 22,610) fielded in Canada across 12 months (April 2020-April 2021) to answer the question "Is there evidence of substantial cross-provincial differences in citizen compliance with basic public health measures designed to prevent the spread of infection?" We find that regional differences in self-reported behaviour are few and very modest, suggesting that interprovincial differences in COVID-19-related health outcomes have little to do with differences in citizen compliance, at least in the first year of the pandemic. These results have important implications. Although it is crucial that we continue to study regional variations related to the COVID-19 burden, public health agency officials, pundits, and politicians should be cautious when musing about the role of citizen compliance as the primary explanation of interprovincial pandemic health outcomes.

L'inégalité des effets de la maladie du coronavirus 2019 (COVID -19) à travers les provinces canadiennes (notamment quant au taux d'infection et de décès) est importante et intrigante. Certains ont postulé que pour mieux comprendre les écarts dans les effets de la pandémie entre les provinces, il faudrait étudier les écarts dans l'application, par les citoyens, des mesures préventives de santé publique. Toutefois, aucun test empirique systématique n'a été effectué pour valider ce postulat. Dans cette recherche, nous utilisons un base de données de taille exceptionnelle, comprenant 23 vagues d'enquêtes (N= 22,610) réalisées sur 12 mois (avril 2020- avril 2021) pour répondre à la question « Existe-t-il une preuve de différences considérables entre les provinces dans l'application par les citoyens des mesures sanitaires de base en vue de prévenir la transmission de l'infection? ¼ Nous constatons que les différences régionales dans le comportement autodéclaré sont très faibles, ce qui veut dire que l'écart des effets de la COVID-19 sur la santé entre les provinces n'avait pas grand-chose à voir avec l'application des mesures par les citoyens, du moins pendant la première année de la pandémie. Ces résultats ont des implications importantes. Même s'il est capital de continuer à étudier les variations régionales reliées au fléau de la COVID-19, les autorités publiques de la santé, les spécialistes et les politiciens, doivent être vigilants quand ils présentent l'application des mesures par les citoyens comme étant la première explication de l'écart des effets sur la santé entre les provinces.

The BC Generations Project as a Tumor Tissue Resource for Cancer Research.

Population-based cohort studies can be a resource for tumor specimens, annotated with demographic, lifestyle, and health history data, that support innovative studies of cancer. Our aim was to establish and test a process for accessing tumor samples, held at pathology laboratories around British Columbia (BC), for participants of the BC Generations Project (BCGP). Through the BC Cancer Registry, we identified pathology reports for 1100 (93%) of the 1180 incident solid cancer cases diagnosed in BCGP as of 2019. Using manually abstracted data from the reports, we successfully retrieved 183 (92%) of the 200 formalin-fixed, paraffin-embedded (FFPE) blocks (breast, lung, bladder, and pancreas cancer cases) that we requested from pathology laboratories. No important differences in retrieval rates by cancer site, sample location (Greater Vancouver vs. Outside Greater Vancouver), sample type (biopsy vs. excision) or year of diagnosis were identified. A text mining solution recently implemented by the Registry will allow us to automate the process for data abstraction and should capture pathology reports for 100% of all newly diagnosed BCGP cancer cases moving forward. This will further enhance the utility of BCGP as a high-quality tumor tissue research resource.

Citizens' Willingness to Support New Taxes for COVID-19 Measures and the Role of Trust.

The COVID-19 public health pandemic has seen governments spend trillions of dollars to limit the spread of the COVID-19 virus as well as to soften the economic blow from the shutting down of national economies. Subsequent budget shortfalls raise the question of how governments will pay for the direct and indirect costs associated with the COVID-19 pandemic. In this article, we study the public's willingness to contribute through paying a new tax, with a focus on Canada. We find that both generalized social and political trust are associated with a greater willingness to support a COVID-related tax and that generalized social trust, in particular, attenuates the negative effect of an experimentally manipulated, specified level of tax burden on policy support. These findings entail important implications for the public opinion and tax policies literature, as well as for policy makers. RELATED ARTICLES: Gainous, Jason, Stephen C. Craig, and Michael D. Martinez. 2008. "Social Welfare Attitudes and Ambivalence about the Role of Government." Politics & Policy 36 (6): 972-1004. https://doi.org/10.1111/j.1747-1346.2008.00147 Shock, David R. 2013. "The Significance of Opposition Entrepreneurs on Local Sales Tax Referendum Outcomes." Politics & Policy 41 (4): 588-614. https://doi.org/10.1111/polp.12028 Wagle, Udaya R. 2013. "The Heterogeneity Politics of the Welfare State: Changing Population Heterogeneity and Welfare State Policies in High-Income OECD Countries, 1980-2005." Politics & Policy 41 (6): 947-984. https://doi.org/10.1111/polp.12053.

VOLUNTAD DE LOS CIUDADANOS PARA APOYAR NUEVOS IMPUESTOS PARA LAS MEDIDAS COVID­19 Y EL PAPEL DE LA CONFIANZA: La pandemia de salud pública COVID­19 hizo que los gobiernos gastaran billones de dólares para limitar la propagación del virus COVID­19, así como para suavizar el golpe económico del cierre de las economías nacionales. Los posteriores déficits presupuestarios plantean la cuestión de cómo pagarán los gobiernos los costos directos e indirectos asociados con la pandemia de COVID­19. En este documento, estudiamos la disposición del público a contribuir mediante el pago de un nuevo impuesto. Encontramos que tanto la confianza social como política generalizada se asocian con una mayor disposición a apoyar un impuesto relacionado con COVID y que la confianza social generalizada en particular atenúa el efecto negativo de un nivel especificado de carga tributaria manipulado experimentalmente sobre el apoyo a las políticas. Estos hallazgos tienen implicaciones importantes para la opinión pública y la literatura sobre políticas fiscales, y también para los responsables de la formulación de políticas.

A guilt-free strategy increases self-reported non-compliance with COVID-19 preventive measures: Experimental evidence from 12 countries.

Studies of citizens' compliance with COVID-19 preventive measures routinely rely on survey data. While such data are essential, public health restrictions provide clear signals of what is socially desirable in this context, creating a potential source of response bias in self-reported measures of compliance. In this research, we examine whether the results of a guilt-free strategy recently proposed to lessen this constraint are generalizable across twelve countries, and whether the treatment effect varies across subgroups. Our findings show that the guilt-free strategy is a useful tool in every country included, increasing respondents' proclivity to report non-compliance by 9 to 16 percentage points. This effect holds for different subgroups based on gender, age and education. We conclude that the inclusion of this strategy should be the new standard for survey research that aims to provide crucial data on the current pandemic.

Unexpected diagnosis of metastatic breast carcinoma in an endomyocardial biopsy done for cardiac allograft rejection evaluation.

We report a case of a 75-year-old female post orthotopic heart transplantation, who presented to the emergency department with a six-week history of shortness of breath, hand tremor and ultimately delirium. She had lobular breast carcinoma more than 5 years prior to her heart transplant, treated by lumpectomy followed by anthracycline based chemotherapy. The reason for her heart transplant was heart failure that was suspected to be from anthracycline cardiomyopathy, however, her explanted heart actually showed cardiac sarcoidosis. She was placed on long-term immunosuppression with tacrolimus, mycophenolate mofetil and prednisone. Two years after her heart transplant, she underwent bilateral mastectomies for recurrent breast cancer. Her neurological workup, including brain imaging (CT, MRI, LP and EEG) did not show any structural abnormalities, ischemia, mass or neurosarcoidosis as cause for delirium. Tacrolimus was held due to renal dysfunction and hemolytic anemia, and then she developed signs of right heart failure so an endomyocardial biopsy was carried out for suspected allograft rejection. The biopsy did not show any evidence of cellular or antibody medicated rejection; however, it demonstrated infiltration by bland appearing cells with signet ring morphology cells many of which showed intracytoplasmic mucin. The cells were strongly positive with cytokeratins AE1/3, CK7 and mammaglobin. The morphology and immunoprofile were consistent with metastatic lobular breast carcinoma and this was thought to be the cause of her clinical presentation with delirium, hemolytic anemia and renal dysfunction as a paraneoplastic syndrome.

Canadian Cardiovascular Society/Canadian Cardiac Transplant Network Position Statement on Heart Transplantation: Patient Eligibility, Selection, and Post-Transplantation Care.

Significant practice-changing developments have occurred in the care of heart transplantation candidates and recipients over the past decade. This Canadian Cardiovascular Society/Canadian Cardiac Transplant Network Position Statement provides evidence-based, expert panel recommendations with values and preferences, and practical tips on: (1) patient selection criteria; (2) selected patient populations; and (3) post transplantation surveillance. The recommendations were developed through systematic review of the literature and using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The evolving areas of importance addressed include transplant recipient age, frailty assessment, pulmonary hypertension evaluation, cannabis use, combined heart and other solid organ transplantation, adult congenital heart disease, cardiac amyloidosis, high sensitization, and post-transplantation management of antibodies to human leukocyte antigen, rejection, cardiac allograft vasculopathy, and long-term noncardiac care. Attention is also given to Canadian-specific management strategies including the prioritization of highly sensitized transplant candidates (status 4S) and heart organ allocation algorithms. The focus topics in this position statement highlight the increased complexity of patients who undergo evaluation for heart transplantation as well as improved patient selection, and advances in post-transplantation management and surveillance that have led to better long-term outcomes for heart transplant recipients.

Chemical Stability of Reconstituted Sincalide in Sterile Water Under 2 Different Storage Conditions.

This study aimed to evaluate the chemical stability of sincalide at 2 common storage conditions-room temperature and refrigeration-in an attempt to simulate the conditions faced during centralized reconstitution and subsequent distribution to regional clinical facilities. Sincalide is a peptide hormone product administered parenterally as an aid for diagnostic imaging of hepatobiliary conditions. With an estimated postreconstitution shelf-life of 8 h (updated by the manufacturer in 2014 with limited supporting data) and frequent shortages due to an intermittent supply, there is both clinical and economic value in the experimental determination of the true chemical stability of this agent. Methods: Sincalide was reconstituted and stored at both temperatures (n = 4 each), and samples were collected at predetermined time points. A validated high-performance liquid chromatography analytic method was used for quantification of the active ingredient in these samples. Results: Little to no chemical degradation of sincalide was observed for the duration of study, over 8 d, after reconstitution and storage at room temperature. A trend toward a cyclic fluctuation in concentration was also shared among all samples. A similar trend toward little to no chemical degradation and cyclic pattern was observed for the duration of study, over 8 d, after reconstitution and storage in refrigeration. Conclusion: This study supports that from a chemical standpoint, sincalide may potentially be used up to at least 8 d after reconstitution with sterile water, thus providing convenience and cost-saving benefits to medical institutions using the product. The findings of this study, however, warrant microbial testing over this storage duration before any recommendations for extended use can be made.

Evaluation of individual and cumulative sites of extrarenal tumor invasion in pT3a clear cell renal cell carcinoma.

INTRODUCTION: The Tumor-Node-Metastasis classification of renal cell carcinoma (RCC) for pT3a tumors includes sinus fat invasion (SFI), perinephric fat invasion (PFI), renal vein invasion (RVI), and/or pelvicaliceal system invasion (PSI). The purpose of this study was to determine the association between these patterns of invasion (assessed individually and cumulatively) with the development of metastases and cancer-specific mortality (CSM). MATERIALS AND METHODS: We identified 160 patients who underwent radical nephrectomy for pT3a clear cell RCC between 2011 and 2017. The association between individual patterns of invasion and metastases and cancer-specific survival were evaluated with multivariate logistic regression. Cox Hazard proportion ratios and Kaplan-Meier survival curves were generated for patterns of invasion (assessed individually and cumulatively). RESULTS: The number of individual invasive patterns was as follows: 97/160 (61%) presented with RVI, 91/160 with SFI (57%), 62/160 with PFI (39%), and 24/160 (15%) with PSI. At multivariate analysis, both PFI and RVI were associated with metastases (P < 0.001 and 0.028, respectively). PFI (hazard ratio [HR] 4.12, 95% confidence interval [CI] 2.14-7.92; P < 0.001), RVI (HR 2.44, 95% CI 1.18-5.01; P = 0.015), SFI (HR 2.13, 95% CI 1.05-4.34; P = 0.036) had higher CSM, while PSI (HR 1.43, 95% CI 0.65-3.16; p = 0.38) did not show increased CSM. Furthermore, cumulative analysis showed that multiple invasive patterns resulted in worse CSM (p < 0.001). CONCLUSIONS: In our study, PFI was associated with the most aggressive behavior while PSI was the most indolent. Furthermore, the presence of more than one pattern of invasion was associated with worse CSM. These results indicate that reporting of the individual location and cumulative amount of pT3a patterns of invasion in clear cell RCC is clinically relevant.

Characteristics and outcomes in a prospective cohort of patients with histologically diagnosed aortitis.

OBJECTIVES: Our aim was to evaluate characteristics and prospective adverse aortic outcomes in a cohort of patients with non-infectious histological aortitis. METHODS: Patients with histological aortitis, diagnosed at the Ottawa Hospital after surgical repair of thoracic aortic aneurysms or dissections, consented to enrolment in a prospective observational cohort. Patients were assessed for an underlying inflammatory condition and followed prospectively with periodic clinical, laboratory and radiographic assessments. Aortic outcomes during follow-up included significant events, defined as new thoracic or abdominal aortic aneurysms, dissections, ruptures or other complications requiring aortic intervention, in addition to aortic branch ectasias, aneurysms and stenosis. RESULTS: Sixteen patients with histological aortitis from surgical procedures performed between 2010 and 2017 were included; nine had idiopathic and seven had secondary aortitis. Idiopathic patients were more likely to have smoked (100 vs 43%, P = 0.02) and had more associated arch or descending aortic aneurysms on pre-operative baseline imaging compared with secondary aortitis (6 vs 0, P = 0.01). At the median 3.6 years of follow-up, eight patients (50%) had 10 significant aortic events. The incidence of aortic dissection was higher in the first year post-surgery, compared with subsequent years, whereas incident aneurysms occurred throughout follow-up. Elevated inflammatory markers during follow-up trended towards association with accumulation of severe aortic damage. CONCLUSION: This is the first reported prospective study in patients with histological aortitis. Within the limitations of a small cohort, we report a high incidence of aortic complications. Studies with a larger sample size and longer follow-up are needed to corroborate these findings.

Lysosomal storage disorders affecting the heart: a review.

Lysosomal storage disorders (LSD) comprise a group of diseases caused by a deficiency of lysosomal enzymes, membrane transporters or other proteins involved in lysosomal biology. Lysosomal storage disorders result from an accumulation of specific substrates, due to the inability to break them down. The diseases are classified according to the type of material that is accumulated; for example, lipid storage disorders, mucopolysaccharidoses and glycoproteinoses. Cardiac disease is particularly important in lysosomal glycogen storage diseases (Pompe and Danon disease), mucopolysaccharidoses and in glycosphingolipidoses (Anderson-Fabry disease). Various disease manifestations may be observed including hypertrophic and dilated cardiomyopathy, coronary artery disease and valvular diseases. Endomyocardial biopsies can play an important role in the diagnosis of these diseases. Microscopic features along with ancillary tests like special stains and ultrastructural studies help in the diagnosis of these disorders. Diagnosis is further confirmed based upon enzymatic and molecular genetic analysis. Emerging evidence suggests that Enzyme replacement therapy (ERT) substantially improves many of the features of the disease, including some aspects of cardiac involvement. The identification of these disorders is important due to the availability of ERT, the need for family screening, as well as appropriate patient management and counseling.

Diffuse Subepicardial Late Gadolinium Enhancement After Heart Transplant: A Potentially Ominous Finding.

Late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging has prognostic utility in populations with cardiac disease, including heart transplant (HT) recipients. The etiology of specific LGE patterns and their correlation with outcomes after HT are unclear. Antibody-mediated rejection and cardiac allograft vasculopathy are major causes of death, and their evaluation remains challenging. We report identical diffuse subepicardial LGE in 2 highly allosensitized HT recipients who developed allograft failure. We postulate this LGE pattern may be related to antibody-mediated rejection and cardiac allograft vasculopathy, and portends poor outcomes. These cases illustrate a potential role of cardiac magnetic resonance for antibody-mediated rejection evaluation and risk stratification.

Transforming the prostatic tumor microenvironment with oncolytic virotherapy.

Prostate cancer (PCa) was estimated to have the second highest global incidence rate for male non-skin tumors and is the fifth most deadly in men thus mandating the need for novel treatment options. MG1-Maraba is a potent and versatile oncolytic virus capable of lethally infecting a variety of prostatic tumor cell lines alongside primary PCa biopsies and exerts direct oncolytic effects against large TRAMP-C2 tumors in vivo. An oncolytic immunotherapeutic strategy utilizing a priming vaccine and intravenously administered MG1-Maraba both expressing the human six-transmembrane antigen of the prostate (STEAP) protein generated specific CD8+ T-cell responses against multiple STEAP epitopes and resulted in functional breach of tolerance. Treatment of mice with bulky TRAMP-C2 tumors using oncolytic STEAP immunotherapy induced an overt delay in tumor progression, marked intratumoral lymphocytic infiltration with an active transcriptional profile and up-regulation of MHC class I. The preclinical data generated here offers clear rationale for clinically evaluating this approach for men with advanced PCa.

Acute Management of Infected Chronic Thromboembolic Disease.

A 29-year-old man with chronic pulmonary emboli presented to the hospital with progressive pleuritic chest pain. He was in acute right ventricular failure and received intrapulmonary arterial tissue plasminogen activator. Massive hemoptysis developed, requiring emergent thromboendarterectomy. A clot was visualized in the main left pulmonary artery that had formed a bronchovascular fistula into the left upper lobe bronchus. Pathology of the clot revealed fibrinopurulent exudate and Gram-positive cocci. The left pulmonary artery was repaired with a pericardial patch, and the left upper lobe was oversewn with subsequent left upper lobectomy. The patient was discharged home on postoperative day 23.

Teens, Drugs, & Vegas: Toxicological surveillance of illicit prescription and illegal drug abuse in adolescents (12-17 years) using post-mortem data in Clark County, Nevada from 2005 to 2015.

Illegal drug abuse, particularly prescription drug abuse is a growing problem in the United States. Research on adolescent drug abuse is based on national self-reported data. Using local coroner data, quantitative prevalence of illegal substance toxicology and trends can be assessed to aid directed outreach and community-based prevention initiatives. Retrospective analysis was conducted on all cases aged 12-17 years referred to the Office of the Medical Examiner, Clark County from 2005 to 2015 (n = 526). The prevalence of illegal opioid use in this population was 13.3%. The most commonly used drug was tetrahydrocannabinol (THC) in 29.7%. Illegal-prescription opioids and benzodiazepines were used approximately 1.7 times as much as all other illegal-drugs, excluding THC combined. The largest proportion of illicit prescription drug users were accidental death victims (p = 0.02, OR = 2.02). Drug trends by youth are ever evolving and current specific data is necessary to target prevention initiatives in local communities.

Abdominal visceral perforation by buried peritoneal dialysis catheters: Cause or coincidence?

Delayed visceral organ perforations after PD catheter insertions are extremely rare. We report two patients who presented with asymptomatic visceral perforation from their buried PD catheters. Five months after a laparoscopic buried PD catheter insertion in a 92-year-old man PD was initiated; bile and bowel contents were noted in the PD effluent. He subsequently expired (from pneumonia) to autopsy revealed the PD catheter within the small bowel. Despite this perforation, there was no evidence of peritonitis, inflammation, nor any bowel content within the peritoneal cavity. A second case was observed 2.5 months after an uncomplicated laparoscopic buried PD catheter insertion in a 60-year-old woman. PD was attempted; the patient had an immediate urge to void. MRI revealed the presence of the PD catheter within her bladder. She underwent PD catheter revision the next day with repair of bladder perforation and ultimately successfully initiated PD. Since the perforations did not occur at the time of catheter placement, we believe that the catheter eroded into a viscus, perhaps related to the lack of a fluid at the catheter - viscus interface. The diagnosis of delayed visceral organ perforation following buried PD catheter insertion may be delayed because the catheter is not immediately used.