Background: Hyperplasia is a common phenomenon in inflamed muscle. Results: IL-1 secreted associated with pyroptotic cell death mediate IGF1-dependent detrusor expansion. Conclusion: Bladder muscle hyperplasia resulting from NLRP3 inflammatory cascade can be attenuated by neutralization of IL-1 and IGF1. Significance: Antagonizing IL-1 can have a therapeutic benefit for subjects with muscle hyperplasia resulting from chronic inflammatory diseases.
Hemorrhagic cystitis is an inflammatory and ulcerative bladder condition associated with systemic chemotherapeutics, like cyclophosphomide. Earlier, we reported reactive oxygen species resulting from cyclophosphamide metabolite, acrolein, causes global methylation followed by silencing of DNA damage repair genes. Ogg1 (8-oxoguanine DNA glycosylase) is one such silenced base excision repair enzyme that can restore DNA integrity. The accumulation of DNA damage results in subsequent inflammation associated with pyroptotic death of bladder smooth muscle cells. We hypothesized that reversing inflammasome-induced imprinting in the bladder smooth muscle could prevent the inflammatory phenotype. Elevated recruitment of Dnmt1 and Dnmt3b to the Ogg1 promoter in acrolein treated bladder muscle cells was validated by the pattern of CpG methylation revealed by bisulfite sequencing. Knockout of Ogg1 in detrusor cells resulted in accumulation of reactive oxygen mediated 8-Oxo-dG and spontaneous pyroptotic signaling. Histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), restored Ogg1 expression in cells treated with acrolein and mice treated with cyclophosphamide superior to the standard of care, mesna or nicotinamide-induced DNA demethylation. SAHA restored cyclophosphamide-induced bladder pathology to that of untreated control mice. The observed epigenetic imprinting induced by inflammation suggests a new therapeutic target for the treatment of hemorrhagic cystitis.
INTRODUCTION AND OBJECTIVES:The evolution of medical technology has had several unanticipated effects as humans interact with mechanical systems. These 'ironies of automation' add complexity to the delivery of medical care and often offset the benefits, especially in the early period of learning. Flow disruptions are deviations in the progress of patient care that can compromise safety and indicate where systems are failing to deliver the best care. We applied the principles of human factors research to robotic prostatectomy in order to better understand the impact of operative urology resident education and improve the quality of patient care and safety.METHODS: We studied flow disruptions that occurred during radical prostatectomy when urology residents participated in surgery. Thirty-four cases were observed over twenty weeks. Flow disruptions were sorted into categories: communication, coordination, instrument changes, surgeon decision-making time, external/extraneous, equipment issues, environment, and patient factors. Analysis of surgical time by surgical phase and rate of flow disruptions was stratified by the presence of urology resident involvement. Four surgical phases were defined: (1) patient entering the operating room to anesthesia induction, (2) trochar placement to robot docking, (3) console time, and (4) robot undocking to patient recovery.RESULTS: Average total operating room time was 302AE76 minutes with an average of 9.2AE3.7 flow disruptions recorded per hour. There were approximately 27 flow disruptions per case. The three most common types of flow disruptions were disruptions of communication, coordination, and equipment. When urology residents participated in the case, there was a statistically significant increase in the rate at which flow disruptions occurred in the third phase of the operation only (12.8AE5.2 versus 10.5AE3.9 flow disruptions per hour, p<0.001). This increase in flow disruption rate with resident participation was not associated with any significant increase in phase-specific or total operating room time.CONCLUSIONS: Flow disruptions occurred predictably during robotic prostatectomy, with interruptions of coordination, equipment, and communication being the most frequent types recorded. However, urology resident participation did not have any significant effect on the duration of surgery. This study should alleviate any concerns and debunk the myth that resident involvement in robotic prostatectomy has any detrimental effect on the flow of intra-operative patient care.
We present a previously undocumented complication of dystrophic calcification of the prostate after cryotherapy. An 87-year-old male presented with recurrent lower urinary tract infections and was found to have an obstructing large calcified mass in the right lobe of the prostate. Subsequently, he underwent transurethral resection of the prostate (TURP) and bladder neck with laser lithotripsy to remove the calculus. We propose that chronic inflammation and necrosis of the prostate from cryotherapy resulted in dystrophic calcification of the prostate. As the use of cryotherapy for the treatment of localized prostate cancer continues to increase, it is important that clinicians be aware of this scenario and the technical challenges it poses.
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