Intraprostatic injection of tranexamic acid to control refractory bleeding while maintaining therapeutic anticoagulation.

Tranexamic acid (TXA) has been used to manage menstrual bleeding and reduce bleeding during orthopedic procedures, but has not been widely used in urology. We present a patient with refractory gross hematuria with required therapeutic anticoagulation who failed multiple other measures to control prostatic bleeding. This patient's hematuria abated with endoscopic localized injection of tranexamic acid into the prostate. The effects were durable with no bleeding recurrence reported while maintaining therapeutic anticoagulation.

Application of a Prognostic Gleason Grade Grouping System to Assess Distant Prostate Cancer Outcomes.

BACKGROUND: There is growing enthusiasm for the adoption of a novel grade grouping system to better represent Gleason scores. OBJECTIVE: To evaluate the ability of prognostic Gleason grade groups to predict prostate cancer (PCa)-specific mortality (PCSM) and bone metastatic progression. DESIGN, SETTING, AND PARTICIPANTS: We identified patients with PCa enrolled in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry across treatment strategies, including conservative and nondefinitive therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We examined the prognostic ability of Gleason grade groups to predict risk of PCSM and bone metastasis using the Kaplan-Meier method and unadjusted and adjusted Cox proportional hazards models. RESULTS AND LIMITATIONS: We identified 10529 men with PCa followed for a median of 81 mo (interquartile range 40-127), including 64% in group I (< 3 + 4); 17% in group II (3+4); 9% in group III (4+3); 6% in group IV (4+4); and 4% in group V (≥ 4 + 5). Relative to grade group I, the unadjusted risks of PCSM and bone metastasis were significantly associated with prognostic grade groupings for both biopsy and prostatectomy samples (all p<0.01). Pairwise comparisons within Gleason sums collapsed within grade group V were not significant; however, this analysis was limited by a small representation of men with Gleason pattern ≥ 4 + 5. CONCLUSIONS: The prognostic grade grouping system is associated with risk of PCSM and metastasis across management strategies, including definitive therapy, conservative management, and primary androgen deprivation. PATIENT SUMMARY: A five-level reporting system for prostate cancer pathology is associated with the risk of late prostate cancer endpoints.

Identifying Prevalence and Risk Factors for Mild Cognitive Impairment in Adults Presenting for Urological Evaluation.

OBJECTIVE: To examine mild cognitive impairment (MCI) in a young and older adult urology population, and which external factors were associated with diminished cognitive status at baseline. METHODS: We enrolled patients >18 years of age presenting to a large, urban tertiary care center for a wide variety of urologic complaints. Cognitive status was determined by the Montreal Cognitive Assessment (MoCA) screening test. A score of 26-30 on the MoCA is considered cognitively intact, whereas <26 indicates MCI. Patient charts were retrospectively reviewed; a backwards-stepwise logistic regression was constructed to compare MCI with potential risk factors. RESULTS: One hundred ninety-seven patients were included. There were 10/33 (30%) patients aged 18-40 who had MCI. Moreover, 32/68 (47%) patients aged 41-64 had MCI. Of older adults age 65+, MCI was seen in 65/96 (68%) patients. Factors associated with MCI in age group 41-64 included opioid use. Patients with stone disease were less likely to demonstrate MCI, when compared to other general categories of urologic chief complaints. For patients in age group 65+, associations with MCI included a cancer-related chief complaint, increased age, depressive symptoms, and less education. There were no significant associations with MCI in age group 18-40. CONCLUSION: These results demonstrate a significant prevalence of MCI in an adult urology population and factors that may be associated with its prevalence. We believe that this study lays the groundwork for urology providers to be able to identify patients who may have MCI at baseline.

Comparative analysis of the efficiency and specificity of myeloid-Cre deleting strains using ROSA-EYFP reporter mice.

Since the first example of conditional gene targeting in mice in 1994, the use of Cre recombinase and loxP flanked sequences has become an invaluable technique to generate tissue and temporal specific gene knockouts. The number of mouse strains expressing floxed-gene sequences, and tissue-specific or temporal-specific Cre-recombinase that have been reported in the literature has grown exponentially. However, increased use of this technology has highlighted several problems that can impact the interpretation of any phenotype observed in these mouse models. In particular, accurate knowledge of the specificity of Cre expression in each strain is critical in order to make conclusions about the role of specific cell types in the phenotypes observed. Cre-mediated deletion specificity and efficiency have been described in many different ways in the literature, making direct comparisons between these Cre strains impossible. Here we report crossing thirteen different myeloid-Cre mouse strains to ROSA-EYFP reporter mice and assaying YFP expression in a variety of naïve unstimulated hematopoietic cells, in parallel. By focusing on myeloid subsets, we directly compare the relative efficiency and specificity of myeloid deletion in these strains under steady-state conditions.

Distinct roles for neutrophils and dendritic cells in inflammation and autoimmunity in motheaten mice.

The motheaten mouse has long served as a paradigm for complex autoimmune and inflammatory disease. Null mutations in Ptpn6, which encodes the nonreceptor protein-tyrosine phosphatase Shp1, cause the motheaten phenotype. However, Shp1 regulates multiple signaling pathways in different hematopoietic cell types, so the cellular and molecular mechanism of autoimmunity and inflammation in the motheaten mouse has remained unclear. By using floxed Ptpn6 mice, we dissected the contribution of innate immune cells to the motheaten phenotype. Ptpn6 deletion in neutrophils resulted in cutaneous inflammation, but not autoimmunity, providing an animal model of human neutrophilic dermatoses. By contrast, dendritic cell deletion caused severe autoimmunity, without inflammation. Genetic and biochemical analysis showed that inflammation was caused by enhanced neutrophil integrin signaling through Src-family and Syk kinases, whereas autoimmunity resulted from exaggerated MyD88-dependent signaling in dendritic cells. Our data demonstrate that disruption of distinct Shp1-regulated pathways in different cell types combine to cause motheaten disease.