Variations and Asymmetry in Sacral Ventral Rami Contributions to the Bladder.

We have demonstrated in human cadavers and canines that nerve transfer to bladder vesical nerve branches is technically feasible for bladder reinnervation after nerve injury. We further clarify here that sacral (S) ventral rami contribute to these vesical branches in 36 pelvic sides (in 22 human cadavers). Gross post-mortem visualization and open anterior abdominal approaches were used, as was micro-CT of sacral nerve bundles, for further confirmation when needed.

Widespread pain phenotypes impact treatment efficacy results in randomized clinical trials for interstitial cystitis/bladder pain syndrome: a Multidisciplinary Approach to the Study of Chronic Pelvic Pain network study.

Pain clinical trials are notoriously complex and often inefficient in demonstrating efficacy, even for known efficacious treatments. A major issue is the difficulty in the a priori identification of specific phenotypes to include in the study population. Recent work has identified the extent of widespread pain as an important determinant of the likelihood of response to therapy, but it has not been tested in clinical trials for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS).

Anatomical Location of the Vesical Branches of the Inferior Hypogastric Plexus in Human Cadavers.

We have demonstrated in canines that somatic nerve transfer to vesical branches of the inferior hypogastric plexus (IHP) can be used for bladder reinnervation after spinal root injury. Yet, the complex anatomy of the IHP hinders the clinical application of this repair strategy. Here, using human cadavers, we clarify the spatial relationships of the vesical branches of the IHP and nearby pelvic ganglia, with the ureteral orifice of the bladder.

Nerve transfer for restoration of lower motor neuron-lesioned bladder, urethral and anal sphincter function. Part 4: Effectiveness of the motor reinnervation.

In pilot work, we showed that somatic nerve transfers can restore motor function in long-term decentralized dogs. We continue to explore the effectiveness of motor reinnervation in 30 female dogs. After anesthesia, 12 underwent bilateral transection of coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves.

Functional mixed effects clustering with application to longitudinal urologic chronic pelvic pain syndrome symptom data.

By clustering patients with the urologic chronic pelvic pain syndromes (UCPPS) into homogeneous subgroups and associating these subgroups with baseline covariates and other clinical outcomes, we provide opportunities to investigate different potential elements of pathogenesis, which may also guide us in selection of appropriate therapeutic targets. Motivated by the longitudinal urologic symptom data with extensive subject heterogeneity and differential variability of trajectories, we propose a functional clustering procedure where each subgroup is modeled by a functional mixed effects model, and the posterior probability is used to iteratively classify each subject into different subgroups. The classification takes into account both group-average trajectories and between-subject variabilities.

Lateralization of bladder function in normal female canines.

This study aimed to identify potential lateralization of bladder function. Electrical stimulation of spinal roots or the pelvic nerve's anterior vesical branch was performed bilaterally in female dogs. The percent difference between the left and right stimulation-induced increased detrusor pressure was determined.

Nerve transfer for restoration of lower motor neuron-lesioned bladder function. Part 1: attenuation of purinergic bladder smooth muscle contractions.

This study determined the effect of pelvic organ decentralization and reinnervation 1 yr later on the contribution of muscarinic and purinergic receptors to ex vivo, nerve-evoked, bladder smooth muscle contractions. Nineteen canines underwent decentralization by bilateral transection of all coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves. After exclusions, 8 were reinnervated 12 mo postdecentralization with obturator-to-pelvic and sciatic-to-pudendal nerve transfers then euthanized 8-12 mo later.

Nerve transfer for restoration of lower motor neuron-lesioned bladder function. Part 2: correlation between histological changes and nerve evoked contractions.

We determined the effect of pelvic organ decentralization and reinnervation 1 yr later on urinary bladder histology and function. Nineteen canines underwent decentralization by bilateral transection of all coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves. After exclusions, eight were reinnervated 12 mo postdecentralization with obturator-to-pelvic and sciatic-to-pudendal nerve transfers, then euthanized 8-12 mo later.

Association of Longitudinal Changes in Symptoms and Urinary Biomarkers in Patients with Urological Chronic Pelvic Pain Syndrome: A MAPP Research Network Study.

Purpose: We analyzed a series of novel noninvasive urinary biomarkers for their ability to objectively monitor the longitudinal clinical status of patients with urological chronic pelvic pain syndrome.

Materials And Methods: Baseline, 6 and 12-month urine samples were collected (216) and used to quantify vascular endothelial growth factor, vascular endothelial growth factor (VEGF) receptor 1 (R1), neutrophil gelatinase associated lipocalin (NGAL), matrix metalloproteinase-2, matrix metalloproteinase (MMP)-9, and MMP-9/NGAL complex by enzyme-linked immunosorbent assays. Patient symptom changes were classified as improved, stable or worse using a functional clustering algorithm.

The Multidisciplinary Approach to The Study of Chronic Pelvic Pain (MAPP) Research Network*: Design and implementation of the Symptom Patterns Study (SPS).

Aims: The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network initiated a second observational cohort study-the Symptom Patterns Study (SPS)-to further investigate the underlying pathophysiology of Urologic Chronic Pelvic Pain Syndrome (UCPPS) and to discover factors associated with longitudinal symptom changes and responses to treatments.

Methods: This multisite cohort study of males and females with UCPPS features a run-in period of four weekly web-based symptom assessments before a baseline visit, followed by quarterly assessments up to 36 months. Controls were also recruited and assessed at baseline and 6 months.

Nerve transfer for restoration of lower motor neuron-lesioned bladder and urethra function: establishment of a canine model and interim pilot study results.

Objective: Previous patient surveys have shown that patients with spinal cord or cauda equina injuries prioritize recovery of bladder function. The authors sought to determine if nerve transfer after long-term decentralization restores bladder and sphincter function in canines.

Methods: Twenty-four female canines were included in this study.

Urologic chronic pelvic pain syndrome: insights from the MAPP Research Network.

Urologic chronic pelvic pain syndrome (UCPPS), which encompasses interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, is characterized by chronic pain in the pelvic region or genitalia that is often accompanied by urinary frequency and urgency. Despite considerable research, no definite aetiological risk factors or effective treatments have been identified. The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network uses a novel integrated strategy to characterize UCPPS as a systemic disorder that potentially involves multiple aetiologies.

Sensory sensitivity and symptom severity represent unique dimensions of chronic pain: a MAPP Research Network study.

Chronic overlapping pain conditions (COPCs) are characterized by aberrant central nervous system processing of pain. This "centralized pain" phenotype has been described using a large and diverse set of symptom domains, including the spatial distribution of pain, pain intensity, fatigue, mood imbalances, cognitive dysfunction, altered somatic sensations, and hypersensitivity to external stimuli. Here, we used 3 cohorts, including patients with urologic chronic pelvic pain syndrome, a mixed pain cohort with other COPCs, and healthy individuals (total n = 1039) from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network to explore the factor structure of symptoms of centralized pain.

Spontaneous passage of ureteral stones in patients with indwelling ureteral stents.

Introduction: To determine rates of spontaneous ureteral stone passage in patients with indwelling ureteral stents, and to identify factors associated with the spontaneous passage of stones while a ureteral stent is in place.

Materials And Methods: From our institutional database, we identified patients who underwent ureteroscopic procedures for stone disease between January 1, 2013 and March 1, 2015. We compared the rates of spontaneous stone passage between patients who had previously undergone ureteral stent placement and those who had not.

Identification of novel non-invasive biomarkers of urinary chronic pelvic pain syndrome: findings from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network.

Objective: To examine a series of candidate markers for urological chronic pelvic pain syndrome (UCPPS), selected based on their proposed involvement in underlying biological processes so as to provide new insights into pathophysiology and suggest targets for expanded clinical and mechanistic studies.

Methods: Baseline urine samples from Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network study participants with UCPPS (n = 259), positive controls (PCs; chronic pain without pelvic pain, n = 107) and healthy controls (HCs, n = 125) were analysed for the presence of proteins that are suggested in the literature to be associated with UCPPS. Matrix metalloproteinase (MMP)-2, MMP-9, MMP-9/neutrophil gelatinase-associated lipocalin (NGAL) complex (also known as Lipocalin 2), vascular endothelial growth factor (VEGF), VEGF receptor 1 (VEGF-R1) and NGAL were assayed and quantitated using mono-specific enzyme-linked immunosorbent assays for each protein.

Use of Age and Medical Comorbidity to Assess Long-term Other-cause Mortality Risk in a Cohort of Men Undergoing Prostate Biopsy at an Academic Medical Center.

Objective: To assess life expectancy and biopsy outcomes in men undergoing prostate biopsy at an academic medical center.

Methods: We analyzed men who underwent prostate biopsy at our medical center between July 2012 and June 2014. Long-term other-cause mortality risk was determined using survival tables.

Painful Bladder Filling and Painful Urgency are Distinct Characteristics in Men and Women with Urological Chronic Pelvic Pain Syndromes: A MAPP Research Network Study.

Purpose: We describe bladder associated symptoms in patients with urological chronic pelvic pain syndromes. We correlated these symptoms with urological, nonurological, psychosocial and quality of life measures.

Materials And Methods: Study participants included 233 women and 191 men with interstitial cystitis/bladder pain syndrome or chronic prostatitis/chronic pelvic pain syndrome in a multicenter study.

The MAPP research network: design, patient characterization and operations.

Background: The "Multidisciplinary Approach to the Study of Chronic Pelvic Pain" (MAPP) Research Network was established by the NIDDK to better understand the pathophysiology of urologic chronic pelvic pain syndromes (UCPPS), to inform future clinical trials and improve clinical care. The evolution, organization, and scientific scope of the MAPP Research Network, and the unique approach of the network's central study and common data elements are described.

Methods: The primary scientific protocol for the Trans-MAPP Epidemiology/Phenotyping (EP) Study comprises a multi-site, longitudinal observational study, including bi-weekly internet-based symptom assessments, following a comprehensive in-clinic deep-phenotyping array of urological symptoms, non-urological symptoms and psychosocial factors to evaluate men and women with UCPPS.

Etiology of chronic prostatitis/chronic pelvic pain syndrome: psychoimmunoneurendocrine dysfunction (PINE syndrome) or just a really bad infection?

Purpose: To review the etiology and pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

Methods: A literature review for the years 1985-2012 was performed using the MEDLINE database of the United States National Library of Medicine.

Results: The evidence for ongoing infection in men with CP/CPPS is lacking.

Gunshot wounds to the scrotum: a large single-institutional 20-year experience.

Unlabelled: Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Penetrating trauma to the scrotum often requires operative intervention, with testicular salvage only possible when enough testicular tissue can be re-approximated in the traumatic setting. The present report represents the largest series of gunshot wound trauma to the scrotum in the literature. Further, it validates recommendations of the European Association of Urology guidelines on urological trauma that advocate operative intervention due to minimal rates of patient morbidity and the inherent limitations of scrotal ultrasonography in discerning testicular compromise.

Feasibility of a femoral nerve motor branch for transfer to the pudendal nerve for restoring continence: a cadaveric study.

Object: Nerve transfers are an effective means of restoring control to paralyzed somatic muscle groups and, recently, even denervated detrusor muscle. The authors performed a cadaveric pilot project to examine the feasibility of restoring control to the urethral and anal sphincters using a femoral motor nerve branch to reinnervate the pudendal nerve through a perineal approach.

Methods: Eleven cadavers were dissected bilaterally to expose the pudendal and femoral nerve branches.

Pregabalin for the treatment of men with chronic prostatitis/chronic pelvic pain syndrome: a randomized controlled trial.

Background: Evidence suggests that the urogenital pain of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) may be neuropathic.

Methods: This randomized, double-blind, placebo-controlled trial was conducted across 10 tertiary care centers in North America to determine whether pregabalin, which has been proved effective in other chronic pain syndromes, is effective in reducing CP/CPPS symptoms. In 2006-2007, 324 men with pelvic pain for at least 3 of the previous 6 months were enrolled in this study.

Central nervous system findings on functional magnetic resonance imaging in patients before and after treatment with anticholinergic medication.

Purpose: Anticholinergic medications are commonly used to treat urinary urgency and frequency. Muscarinic receptors are located in areas beyond the detrusor muscle. In this study we measured changes in central nervous system activity in patients with lower urinary tract symptoms treated with tolterodine or a placebo.