An evaluation of three validated comorbidity indices to predict short-term postoperative outcomes after prosthetic urologic surgery.

PURPOSE: Commonly used comorbidity indices include the Charlson Comorbidity Index (CCI), Elixhauser/Van Walraven Index (VWI), and modified frailty index (mFI). This study evaluates whether these indices predict postoperative readmissions and complications after inflatable penile prosthesis (IPP) and artificial urinary sphincter (AUS) placement. METHODS: We identified adult males who underwent IPP or AUS placement using the State Inpatient and State Ambulatory Surgery and Services Databases for Florida (2010-2015) and California (2010-2011). CCI, VWI, and mFI scores were calculated for each patient. We extracted 30-day emergency department services, 30-day readmissions, 90-day device complications (e.g., removal, replacement, or infection), and 90-day postoperative complications (excluding device complications). Receiver-operating characteristic curves were constructed and areas under the curve (AUC) were compared between the indices using the VWI as the reference model. We considered an AUC < 0.7 to represent poor predictive power. RESULTS: We identified 4242 IPP and 1190 AUS patients. All three indices had AUCs and 95% confidence intervals less than 0.70 for all outcomes following IPP and AUS placement making these indices poor predictors for postoperative outcomes. There were no significant differences in predicting 90-day postoperative complications between the VWI (AUC = 0.59, 95% CI [0.54-0.63]), CCI (AUC = 0.59, 95% CI [0.54-0.63], p = 0.99), and mFI (AUC = 0.60, 95% CI [0.55-0.66], p = 0.53) for IPPs and VWI (AUC = 0.54, 95% CI [0.47-0.61]), CCI (AUC = 0.50, 95% CI [0.43-0.57], p = 0.30), and mFI (AUC = 0.52, 95% CI [0.43-0.60], p = 0.56) for AUS placements. CONCLUSION: All three comorbidity indices were poor predictors of readmissions and complications following urologic prosthetic surgeries. A better comorbidity index is needed for risk-stratification of patients undergoing these surgeries.

Pelvic Extirpative Surgery for the "End-Stage Irradiated Bladder".

Men with prostate cancer have the daunting task of selecting from multiple modalities of treatment. The long-term effects of radiation therapy are only now being recognized. For both patients and surgeons, the end-stage irradiated bladder poses numerous problems and challenges. Specifically, irradiated bladders with urosymphyseal fistula, radiation cystitis, and rectourethral fistula are challenging to manage and treat. This review outlines the presentation, workup, and management including cystectomy for these three devastating late complications of radiation therapy. There are special considerations when performing benign cystectomy that are not typically considered during oncologic cystectomy. We discuss an overview of the current literature regarding the "end-stage bladder" resulting from radiation therapy and the important considerations that must be acknowledged when managing these patients. It is shown that many of the less invasive and conservative options ultimately lead to cystectomy. Indeed, our review concludes that cystectomy with urinary diversion is a safe and viable option in select irradiated patients with the goal to improve quality of life.

Infection rates following urologic prosthetic revision without replacement of any device components compared to partial or complete device exchange: a single-center retrospective cohort study.

Urologic implant revision carries a higher infection risk than virgin implantation. Historically, exchanging device components at the time of revision was performed to reduce infection risk. We hypothesize that revision without replacement of any parts of the device may not be associated with increased infection risk. A single-center, retrospective cohort study was performed on patients undergoing urologic implant revision from 2000 to 2021. Revisions involving exchange of any/all device components (+CE) were compared to revisions without exchange of any components (-CE). The primary outcome was infection or erosion within 12 weeks of revision. Infection rates were compared using Fischer exact test. Infection-free survival (IFS) was compared with Kaplan-Meier (KM) log-rank test and Cox proportional hazards (CPH) model. 551 revisions were included, including 497 revisions with CE and 54 without CE. Among those with at least 12 weeks follow-up, no difference was seen in infection rates within 12 weeks of revision [-CE 3/39 (7.7%) vs. +CE 10/383 (2.6%)], p = 0.109). In addition, IFS was comparable between groups (log-rank test p = 0.22, HR for -CE 1.65 (0.65-4.21). Revision surgery for IPP or AUS without CE may not present an elevated risk of infection in the properly selected patient.

Outcomes of an Algorithmic, Multidisciplinary Approach to Rectourethral Fistula Repair: A Pre- and Postintervention Quasi-Experimental Study.

BACKGROUND: Rectourethral fistulas are a rare yet severe complication of prostate surgery, pelvic irradiation therapy, or both. Multiple surgical repairs exist with widely varying success rates. OBJECTIVE: This study aimed to present our institutional multidisciplinary algorithm for rectourethral fistula repair and its outcomes. DESIGN: This was a retrospective, pre- and postintervention, quasi-experimental design, comparing the frequency of fistula healing and reversal of urinary and fecal diversion before and after implementation of our algorithm. SETTING: All patients who presented to the Duke University with rectourethral fistula between 2002 and 2019 were included. PATIENTS: This study included 79 patients treated for rectourethral fistula: 36 prealgorithm and 43 postalgorithm. INTERVENTIONS: Our multidisciplinary algorithm was implemented in 2012. Patients with fistulas <2 cm and without history of radiation therapy underwent York-Mason repair, whereas those with fistulas 2-3 cm or with prior irradiation underwent transperineal repair with gracilis flap interposition. Those with nonrepairable fistulas (>3 cm or fixed tissues) underwent pelvic exenteration. Before repair, the algorithm recommended all patients to undergo urinary and bowel diversion. MAIN OUTCOME MEASURES: The 2 primary outcomes were rectourethral fistula healing, defined as both radiographic and clinical resolutions, and reversal of urinary and fecal diversions. RESULTS: Frequency of fistula healing improved in the post- versus prealgorithm subgroups (93.1% vs 71.9%; p = 0.04). The relative risk of fistula healing pre- versus postintervention was 0.77 (0.61-0.98; p = 0.04) among the overall cohort. Eighteen patients (22.8%) underwent pelvic exenteration for nonrepairable fistulas and were not included in primary outcome measures. LIMITATIONS: Limitations include the study's retrospective nature, possible selection bias because of algorithmic patient selection, and small sample size. CONCLUSIONS: Implementation of a multidisciplinary institutional algorithm improved rectourethral fistula repair success with high rates of ostomy reversal. Proper patient selection and multidisciplinary involvement are paramount to this success. See Video Abstract at http://links.lww.com/DCR/B955 . RESULTADOS DE UN ABORDAJE ALGORTMICO Y MULTIDISCIPLINARIO PARA LA REPARACIN DE FSTULAS RECTOURETRALES UN ESTUDIO CUASIEXPERIMENTAL PREVIO Y POSTERIOR A LA INTERVENCIN: ANTECEDENTES:Las fístulas rectouretrales son una complicación rara pero grave de la cirugía de próstata, la radiación pélvica o ambas. Existen múltiples reparaciones quirúrgicas con tasas de éxito muy variables.OBJETIVO:Presentar el algoritmo multidisciplinario de nuestra institución para la reparación de fístulas rectouretrales y sus resultados.DISEÑO:Este fue un diseño retrospectivo, previo y posterior a la intervención, cuasiexperimental, que comparó la frecuencia de curación de la fístula y la reversión de la derivación urinaria y fecal antes y después de la implementación de nuestro algoritmo.ESCENARIO:Se incluyeron todos los pacientes que acudieron a Duke con fístula rectouretral entre 2002 y 2019.PACIENTES:Setenta y nueve pacientes fueron tratados por fístula rectouretral; 36 pre-algoritmo y 43 post-algoritmo.INTERVENCIONES:Nuestro algoritmo multidisciplinario se implementó en 2012. Los pacientes con fístulas <2 cm y sin antecedentes de radiación se sometieron a reparación de York-Mason, mientras que aquellos con fístulas de 2-3 cm o radiación pélvica previa se sometieron a reparación transperineal con interposición de colgajo de gracilis. Aquellos con fístulas no reparables (> 3 cm o tejidos fijos) fueron sometidos a exenteración pélvica. Antes de la reparación, el algoritmo recomomendó que todos los pacientes se sometieran a una derivación urinaria y fecal.PRINCIPALES MEDIDAS DE RESULTADO:Los dos resultados primarios fueron la curación de la fístula rectouretral, definida como la resolución radiográfica y clínica, y la reversión de las derivaciones urinaria y fecale.RESULTADOS:La frecuencia de curación de la fístula mejoró en el subgrupo post-algoritmo vs. pre-algoritmo (93.1% vs. 71.9%, p = 0.04). El riesgo relativo de curación de la fístula antes de la intervención en comparación con después de la intervención fue de 0.77 (0.61-0.98, p = 0.04) entre la cohorte general. Dieciocho pacientes (22.8%) se sometieron a exenteración pélvica por fístulas no reparables y, por lo tanto, no se incluyeron en las medidas de resultado primarias.LIMITACIONES:Las limitaciones de este estudio incluyen su naturaleza retrospectiva, posible sesgo de selección debido a la selección algorítmica de pacientes y un tamaño de muestra pequeño.CONCLUSIONES:La implementación de un algoritmo institucional multidisciplinario mejoró el éxito en la reparación de la fístula rectouretral con altas tasas de reversión de la ostomía. La selección adecuada de pacientes y la participación multidisciplinaria son fundamentales para este éxito. Consulte Video Resumen en http://links.lww.com/DCR/B955 . (Traducción-Dr. Jorge Silva Velazco ).

Resection of Pubic Symphysis and Cystectomy Significantly Improves Short-Term Patient-Reported Physical Functioning Among Patients With Pubovesical Fistula and Pubic Bone Osteomyelitis.

OBJECTIVE: To investigate the impact of extirpative surgery for pubic bone osteomyelitis with pubovesical fistula on prostate cancer survivors' physical and mental health. MATERIALS AND METHODS: The Short Form 12 (SF-12) is a validated instrument for assessing health-related quality of life (HRQOL). We reviewed a prospectively maintained database of patients treated with extirpative surgery for pubovesical fistula from 2017-2021 who completed the SF-12. Wilcoxon signed-rank and McNemar's tests were used to analyze changes in SF-12 following surgery. Narcotic prescriptions in the year before and after surgery were assessed as an additional measure of pain burden. RESULTS: Eighteen patients were included. Four had pre-operative SF-12s, 3 had post-operative SF-12s, and 11 had both. Median age was 76.5 years (IQR 71.75-80.00). All patients had previous radiation for prostate cancer. Compared to global pre-operative scores, post-operative physical composite scores (PCS) significantly increased (29.95 ± 8.59 vs 42.48 ± 7.18; P <.001), but mental composite scores (MCS) were similar (45.35 ± 9.98 vs 52.21 ± 8.23). When comparing individual, paired pre-operative and post-operative scores there was a significant improvement in PCS (30.56 ± 9.87 vs 45.45 ± 8.56; P = .005), but not MCS (47.49 ± 6.92 vs 51.60 ± 8.88). Median morphine milligram equivalent significantly decreased in the year post-surgery compared to the year prior (103.1, 33.0-250.9 vs 34.25, 0.0-105.9; P = .0008). CONCLUSION: For prostate cancer survivors with pubovesical fistula and pubic bone osteomyelitis, urinary diversion with pubic bone resection improves physical functioning and decreases narcotic prescriptions without untoward effects on mental health.

Patient-Reported and Physiologic Outcomes Following Pelvic Exenteration for Non-Repairable Radiated Rectourethral Fistula.

OBJECTIVE: To investigate the impact of pelvic exenteration (PelvEX) on patient-reported pain, distress, and quality of life along with physiologic indicators of health in cancer survivors with radiated, non-repairable rectourethral fistula (RUF). MATERIALS AND METHODS: We reviewed a prospectively maintained quality improvement database of RUF patients at our institution from 2012 to 2020. Patients with radiated, non-repairable RUF who underwent PelvEX and had follow up to 1 year were included. Pain and distress scores were collected preoperatively and at 1-year follow up. Number of narcotic prescriptions in the 3 months before surgery and the year after surgery were abstracted. Short Form 12 surveys were administered in the postoperative period. Serum albumin, creatinine, carbon dioxide, hematocrit, and glucose were abstracted from electronic health records. Statistical analysis was performed using Wilcoxon signed-rank and Mann-Whitney tests. RESULTS: Eleven patients met inclusion criteria. Patient-reported pain significantly decreased at 1 year follow-up compared to preoperative scores (median pre: 4 vs 1 year post: 0, P = .0312). Patient-reported distress significantly decreased pre- versus post-PelvEX (median pre: 5 vs post: 0, P = .0156). At the time of postoperative pain and distress surveys, 9 (82.8%) patients did not have narcotic prescriptions. Postoperative Short Form 12 scores were similar to an age-matched United States population (mental: P = .3125; physical: P = .1484). Serum-based indicators of health were not different in the pre- versus postoperative period (all P >.05). CONCLUSION: PelvEX may be a valuable treatment option to decrease patient-reported pain and distress without compromising quality of life or physiologic health in patients with radiated, non-repairable RUF.

Buccal Reharvest for Urethroplasty After Graft Site Closure is Safe and Does Not Affect Long-Term Oral Health.

OBJECTIVE: To understand the effects of reharvest on safety and long-term oral health in patients requiring buccal mucosa reharvest from a previously harvested and closed site for management of recurrent urethral stricture disease. METHODS: We conducted an IRB approved retrospective chart review from 2014 to 2019 of all patients who underwent buccal graft urethroplasty at our referral based academic medical center. Surgical data was collected, and the validated Oral Health Impact Profile (OHIP-14) survey was administered to each patient. Descriptive statistics were performed and compared between patients who underwent a buccal graft reharvest and patients who underwent standard first time buccal harvest. Buccal graft beds were closed on both initial and reharvest. RESULTS: Four patients underwent a total of 5 ipsilateral buccal graft reharvests and 6 patients underwent first time buccal harvest. Median length of follow-up for all patients was 6 months (1-35 mo) and the median length of all grafts was 6 cm (5-6 cm) with no difference in the reharvest and first-time cohorts. For patients that underwent buccal reharvest, their median post-operative OHIP-14 score was 0 (0-9 pts) out of a possible 56 points. This compared to a median postoperative OHIP-14 score of 0 (0-10 pts) for patients who underwent first time buccal harvests with oral complications limited to one post-operative hematoma in the first-time cohort. CONCLUSION: Buccal grafts can safely be reharvested from a previous site with minimal concern for long-term oral health outcomes.

The male sling for stress urinary incontinence: tips and tricks for success

ABSTRACT Urethral slings are a good treatment option for mild male stress urinary incontinence. There are many different sling options, but herein our group describes our techniques with the Advance® and Virtue® slings. More important than technique, we strongly think that patient selection is paramount to sling success. We only offer slings to patients who have low 24 hour pad weights, high Valsalva leak point pressure, and no history of pelvic radiation. Still, like with any surgery, we recommend that the surgeons implant the device that they are most comfortable with along with their chosen techniques.

The male sling for stress urinary incontinence: tips and tricks for success.

Urethral slings are a good treatment option for mild male stress urinary incontinence. There are many different sling options, but herein our group describes our techniques with the Advance® and Virtue® slings. More important than technique, we strongly think that patient selection is paramount to sling success. We only offer slings to patients who have low 24 hour pad weights, high Valsalva leak point pressure, and no history of pelvic radiation. Still, like with any surgery, we recommend that the surgeons implant the device that they are most comfortable with along with their chosen techniques.

Use of isotonic contrast solution in the artificial urinary sphincter does not impact device longevity.

AIMS: The artificial urinary sphincter (AUS), the gold standard for treatment of male stress urinary incontinence, can be filled with normal saline (NS) or isotonic contrast solution. Surgeons have voiced concerns about the impact on device malfunction and longevity, but no studies address this issue. We used industry data to identify differences in outcomes between NS and contrast-filled AUS. METHODS: Our analysis included all men patients in the industry who maintained the AUS database (Boston Scientific) from 2001 to 2016. Patients were divided into two groups: AUS filled with NS or contrast. Patient demographics and device characteristics were compared. Device survival was defined as time to the need for reoperation. We compared device survival between AUS filled with NS versus contrast using a Kaplan-Meier curve adjusted for age, cuff size, and pressure regulating balloon (PRB) size. RESULTS: A total of 39,363 patients were included. 34,674 (88.1%) devices were filled with NS. The reoperation rate overall was 24.5%, with no difference between groups. The mean time to reoperation overall was 3 years (±3.0). After adjustment for age, cuff size, and PRB size, Kaplan-Meier analysis demonstrated a similar time to reoperation between the two groups. CONCLUSION: The use of contrast in the AUS does not appear to change rates of the device malfunction, fluid loss, or need for reoperation. Since filling the device with contrast does not appear inferior to saline in terms of longevity, we feel this should be considered a safe tool for the implanting surgeon.

Increasing Comorbidity and Frailty is Not Associated with Early Postoperative Complications among Men Undergoing Artificial Urinary Sphincter or Sling Implantation: A Real-World Application of NSQIP® Data to Reconstructive Urology.

INTRODUCTION: Urologists may be hesitant to surgically treat urinary incontinence in comorbid genitourinary cancer survivors. We assessed the relationship between comorbidities and 30-day perioperative outcomes following artificial urinary sphincter and sling implantation. METHODS: Using the National Surgical Quality Improvement Program, patients with CPT codes for artificial urinary sphincter and sling implantation were identified between 2007 and 2015. The patient's Charlson comorbidity index and Frailty Index scores were calculated based on ICD-9 codes. The primary outcome was presence of perioperative complications. The association between Charlson comorbidity index and Frailty Index and each primary outcome was investigated using multivariate logistic regression models. RESULTS: We queried 1,370 and 1,018 records with artificial urinary sphincter and sling implantation, respectively. The median Charlson comorbidity index for artificial urinary sphincter patients was 4.0 (Q1 3, Q3 5), while for sling patients it was 3.0 (Q1 3, Q3 4). In the artificial urinary sphincter cohort, 47% had 1 Frailty Index condition, whereas 25% had 2 or more Frailty Index conditions. In the sling group, 42% had 1 Frailty Index condition, while 19% had 2 or more Frailty Index conditions. The event rate for overall complications was 5.4% and 3.0% in the artificial urinary sphincter and sling cohort, respectively. After adjusting for covariates in both the artificial urinary sphincter and sling cohort Charlson comorbidity index or Frailty Index was not associated with the odds of having a complication. CONCLUSIONS: The presence of increased comorbidities or frailty is not associated with short-term postoperative complications among men undergoing artificial urinary sphincter or sling implantation.

Extirpative Cultures Reveal Infectious Pubic Bone Osteomyelitis in Prostate Cancer Survivors With Urinary-Pubic Symphysis Fistulae (UPF).

OBJECTIVE: To examine the infectious features of patients with urinary pubic symphysis fistula (UPF) and their association with osteomyelitis. METHODS: We conducted a review of our quality improvement database for 36 patients with UPF undergoing bone resection and extirpative surgery from October 2012 to January 2019. An assessment of bone and urine cultures was carried out along with surgical, radiologic, and demographic data. We analyzed descriptive statistics and used Fisher Exact Tests and unpaired Welch t tests to assess for associations with positive bone cultures. RESULTS: In our cohort, 33 patients (91.7%) had positive bone cultures with the 3 most common organisms being candida (22.0%), enterococcus (18.0%), and pseudomonas (10.0%). There was a correlation between positive preoperative urine culture and positive bone culture (P <.01), with 63.0% of those with positive urine cultures growing the same organism on bone culture. CONCLUSION: In this series, 91.7% of patients undergoing extirpative surgery for UPF at our institution have positive bone cultures at time of pubic bone debridement. Additionally, we demonstrate a statistically significant correlation between positive urine cultures and positive bone cultures in these patients. This supports the need for a multidisciplinary approach including infectious disease, orthopedic surgery and reconstructive urology in order to address this complex clinical condition.

Intraurethral catheter placement does not change the external circumferential measurement of the urethra during AUS placement: A prospective observational trial.

AIMS: Measuring the urethral circumference accurately during artificial urethral sphincter (AUS) placement is an important technical aspect to optimize the selection of cuff size. Differing methods exist for this step with some experts recommending measurement with no urethral catheter in place. In this prospective observational trial, we compared urethral measurements with and without an indwelling catheter to determine if the presence of a catheter affects the circumferential measurement. METHODS: With IRB approval, we prospectively collected data on consecutive cases of transperineal male AUS implantation. Urethral circumference was measured with no urethral catheter (0 French [Fr]), 12Fr, and 16Fr Foley catheters in the urethra. The final measurements and cuff size chosen were recorded. A comparison was made between each measurement using Spearman's correlation coefficient. RESULTS: A total of 54 patients were included, the majority of whom (92.6%) underwent AUS placement for postprostatectomy incontinence. The three urethral circumference measurements were highly correlated (0Fr vs 12Fr, ρ = 0.96, P < .001, mean difference 1 mm) (0Fr vs 16Fr, ρ = 0.94, P < .001, mean difference 2 mm) (12Fr vs 16Fr, ρ = 0.96, P < .001, mean difference 1 mm). Patients with a history of radiation had a lower mean urethral circumference than those who had never been radiated (4.78 cm vs 5.3 cm, P = .01). CONCLUSIONS: Urethral circumference measurement during AUS implantation is not influenced by the presence of a 12 or 16Fr Foley catheter when compared to no catheter in the urethra. Measurement of the urethral circumference can, therefore, be accurately performed with or without a catheter in place, depending on the surgeon's preference.

National Imaging and Antibiotic Practice Patterns in Children Presenting With Urinary Tract Infection to Community Practices: Little Impact From the American Academy of Pediatrics Guidelines?

Our objective was to use community-based, national databases to evaluate diagnostic imaging and antibiotic prophylaxis practice patterns before and after the release of the 2011 American Academy of Pediatrics guidelines for acute febrile urinary tract infection. Using the National Ambulatory and Hospital Ambulatory Medical Care Surveys, urinary tract infection encounters were identified for patients aged 2 months to 18 years. Primary outcomes were utilization of antibiotics (as proxy for prophylaxis) and diagnostic imaging during encounters. Weighted multivariate logistic regression models were used to examine the association between time period (before and after 2011) and each of the primary outcomes. Among 8 588 035 weighted encounters, adjusting for covariates, there was insufficient evidence to suggest a difference between time periods for antibiotic utilization (odds ratio = 0.66, P = .12) or diagnostic imaging (odds ratio = 1.16, P = .56). Thus, we did not find evidence of changes in antibiotic utilization or diagnostic imaging practice patterns after the release of the 2011 American Academy of Pediatrics guidelines.

Hospital and ED charges for spina bifida care in the United States between 2006 and 2014: Over $2 billion annually.

BACKGROUND: More children with spina bifida (SB) are surviving into adulthood. Unfortunately, little data exist regarding the economic implications of modern SB care. OBJECTIVE: We examined economic data from two national databases to estimate the annual nationwide hospital and emergency charges of SB from 2006-14. METHODS: We analyzed the 2006-2014 Nationwide Inpatient Sample (NIS) and Nationwide Emergency Department Sample (NEDS). SB patients were defined using ICD-9-CM codes. Demographic and charge data were obtained from each database. Multiple imputation was used to estimate missing data (1.6% for NIS and 22% in NEDS). The principal outcomes were mean, median, and total charges for encounters each year. RESULTS: There were 725,646 encounters for individuals with SB between 2006 and 2014. The average age of captured SB patients who were admitted to a hospital or seen in an ER was 29 years. In 2014, the median charge for inpatient encounters was $31,071 (IQR: $15,947, $63,063) and for ER encounters was $2407.02 (IQR: $1321.91, $4211.35). In total, the sum of charges from all SB-related admissions in 2014 was $1,862,016,217 (95% CI: $1.69 billion, $2.03 billion), while the sum of charges of all SB-related ER encounters in 2014 was $176,843,522 (95% CI: $158 million, $196 million). There was a steady increase in charges over the study period. CONCLUSION: Charges for SB-related inpatient and emergency care in the US in 2014 was in excess of $2 billion in contrast to $1.2 billion in 2006, after adjusting for inflation; this is an impressively high figure for a relatively small number of patients.

NLRP3 Promotes Diabetic Bladder Dysfunction and Changes in Symptom-Specific Bladder Innervation.

The NLRP3 inflammasome senses diabetic metabolites and initiates inflammation implicated in diabetic complications and neurodegeneration. No studies have investigated NLRP3 in diabetic bladder dysfunction (DBD), despite a high clinical prevalence. In vitro, we found that numerous diabetic metabolites activate NLRP3 in primary urothelial cells. In vivo, we demonstrate NLRP3 is activated in urothelia from a genetic type 1 diabetic mouse (Akita) by week 15. We then bred an NLRP3-/- genotype into these mice and found this blocked bladder inflammation and cystometric markers of DBD. Analysis of bladder innervation established an NLRP3-dependent decrease in overall nerve density and Aδ-fibers in the bladder wall along with an increase in C-fiber populations in the urothelia, which potentially explains the decreased sense of bladder fullness reported by patients and overactivity detected early in DBD. Together, the results demonstrate the role of NLRP3 in the genesis of DBD and suggest specific NLRP3-mediated neuronal changes can produce specific DBD symptoms.

Diabetic bladder dysfunction is associated with bladder inflammation triggered through hyperglycemia, not polyuria.

PURPOSE: Diabetes is a grave and progressive condition characterized by debilitating complications. Diabetic bladder dysfunction (DBD) is a very common complication with no specific treatments currently available. Unlike other tissues affected by this disease, the bladder is subjected to two independent insults; 1) polyuria, created by the osmotic effects of glucose in the urine, and 2) hyperglycemia itself. Based on our understanding of inflammation as a major contributor to the underlying organ damage in several other diabetic complications, its presence in the bladder during DBD and the contribution of polyuria and hyperglycemia to its development were assessed. METHODS: Awake, restrained cystometry was performed on wild type C57BL/6 mice and diabetic (Akita) mice on a C57BL/6 background at 15 weeks of age. A subgroup of the Akita mice were treated with phlorizin, an inhibitor of sodium-glucose linked transporter types 1 and 2 that prevents glucose reabsorption in the kidney. All groups were assessed for serum glucose, 4-hour voiding totals, and inflammation in the bladder (Evans blue assay). RESULTS: Akita mice develop cystometrically-defined DBD by 15 weeks of age, as evidenced by an increase in urinary frequency, a decrease in voiding volume, and an increase in post-voiding residual volume. Phlorizin effectively normalized serum glucose in these animals while increasing the urine output. Inflammation in the bladder was present in the diabetic animals at this time point, but not detectable in animals receiving phlorizin. CONCLUSION: Inflammation in the bladder of diabetic mice correlates with the development of DBD and is triggered by hyperglycemia, not polyuria.