Bacterial Interactions as Detected by Pooled Antibiotic Susceptibility Testing (P-AST) in Polymicrobial Urine Specimens.

Introduction: Antimicrobial susceptibility is well characterized in monomicrobial infections, but bacterial species often coexist with other bacterial species. Antimicrobial susceptibility is often tested against single bacterial isolates; this approach ignores interactions between cohabiting bacteria that could impact susceptibility. Here, we use Pooled Antibiotic Susceptibility Testing to compare antimicrobial susceptibility patterns exhibited by polymicrobial and monomicrobial urine specimens obtained from patients with urinary tract infection symptoms. Methods: Urine samples were collected from patients who had symptoms consistent with a urinary tract infection. Multiplex polymerase chain reaction testing was performed to identify and quantify 31 bacterial species. Antibiotic susceptibility was determined using a novel Pooled Antibiotic Susceptibility Testing method. Antibiotic resistance rates in polymicrobial specimens were compared with those in monomicrobial infections. Using a logistic model, resistance rates were estimated when specific bacterial species were present. To assess interactions between pairs of bacteria, the predicted resistance rates were compared when a pair of bacterial species were present versus when just one bacterial species was present. Results: Urine specimens were collected from 3,124 patients with symptoms of urinary tract infection. Of these, multiplex polymerase chain reaction testing detected bacteria in 61.1% (1910) of specimens. Pooled Antibiotic Susceptibility Testing results were available for 70.8% (1352) of these positive specimens. Of these positive specimens, 43.9% (594) were monomicrobial, while 56.1% (758) were polymicrobial. The odds of resistance to ampicillin (p = 0.005), amoxicillin/clavulanate (p = 0.008), five different cephalosporins, vancomycin (p = <0.0001), and tetracycline (p = 0.010) increased with each additional species present in a polymicrobial specimen. In contrast, the odds of resistance to piperacillin/tazobactam decreased by 75% for each additional species present (95% CI 0.61, 0.94, p = 0.010). For one or more antibiotics tested, thirteen pairs of bacterial species exhibited statistically significant interactions compared with the expected resistance rate obtained with the Highest Single Agent Principle and Union Principle. Conclusion: Bacterial interactions in polymicrobial specimens can result in antimicrobial susceptibility patterns that are not detected when bacterial isolates are tested by themselves. Optimizing an effective treatment regimen for patients with polymicrobial infections may depend on accurate identification of the constituent species, as well as results obtained by Pooled Antibiotic Susceptibility Testing.

Transvaginal Trigger Point Injections Improve Pain Scores in Women with Pelvic Floor Hypertonicity and Pelvic Pain Conditions.

OBJECTIVES: Chronic pelvic pain in women often requires multimodal treatment regimens. We describe our method of transvaginal trigger point injections (TPIs) and report outcomes using change in pain scores. METHODS: This was a retrospective review of women treated with in-office pelvic floor muscle injections from January 2012 to August 2015. Lidocaine 1% and 2%, bupivacaine 0.5%, or ropivacaine 0.5% with or without the addition of triamcinolone 40 mg was used for the injections. Pain was reported on a 0- to 10-point numerical rating scale before and after injection. Differences in pretreatment and posttreatment pain scores were analyzed after the first injection and after subsequent injections. Repeated-measures analysis was used to determine if any variable affected treatment response. RESULTS: One hundred one women with a mean age of 44 years had a total of 257 separate visits for pelvic floor muscle injections. Triamcinolone was used at 90.2% (230/255) of the TPI visits. After the initial TPI visit, there was significant decrease in total levator numerical rating scale score (maximum score, 20; mean, -6.21 ± 4.7; P < 0.0001), and 77% (70/91) of patients had improved. These significant improvements were noted at all visits 1 through 4 and whether bilateral or unilateral injections were done. Only the total amount of local anesthestic used had a significant effect on the change in total levator pain scores (P = 0.002). Minor adverse effects including leg numbness, dizziness, nausea, bleeding, and headache occurred at 10% of visits. CONCLUSIONS: Pelvic floor muscle injections decrease pain levels in women with pelvic floor dysfunction.

Does sex matter? A matched pairs analysis of neuromodulation outcomes in women and men.

AIMS: To evaluate whether baseline symptoms and outcomes are influenced by gender in a matched cohort undergoing neuromodulation. METHODS: Patients in our prospective neuromodulation database that had a tined lead placed were reviewed. Those that had implantable pulse generator (IPG) placed were matched on age and urologic diagnosis. History, voiding diaries, satisfaction, Interstitial Cystitis Symptom/Problem Index (ICSIPI), and overactive bladder symptom severity (OABq ss)/health-related quality of life (HRQOL) preimplant and over 3 years were evaluated using descriptive statistics, repeated measures, and matched pair GEE or mixed analyses. RESULTS: Of 590 patients in the database, more women than men received an IPG (450/488; 92.2 vs. 84/102; 82.4%; p = 0.0011). Eighty matched pairs (n = 160; 81% ≥ 50 years old; 56.25% had urgency/frequency with urge incontinence-UI) were identified and evaluated. On voiding diaries, volume/void was greater in women only at baseline (p = 0.040); both groups improved over time (p < 0.0001). Urinary frequency improved in both women and men (p = 0.0010; p = 0.0025). Over 3 years, UI episodes/day improved only in men (p = 0.017) and UI severity improved only in women (p < 0.0001). ICSIPI, OABq ss, and HRQOL scores improved similarly in both groups (p < 0.0001 for all measures in both groups), and although more women were satisfied at 3 months (p = 0.027), groups did not differ at other time points. CONCLUSIONS: More women undergo neuromodulation and have initial success and subsequent IPG implantation. UI episodes improved only in men, and UI severity improved only in women. Both women and men experienced similar levels of symptom improvement on other measures.

Pudendal Neuromodulation as a Treatment for Persistent Genital Arousal Disorder-A Case Series.

BACKGROUND: Persistent genital arousal disorder (PGAD) is a rare life-altering condition characterized by unwanted, uncomfortable genital sensations or spontaneous orgasms without physical or emotional stimulation. Its etiology remains unclear, and a variety of treatments have been attempted with incomplete resolution. We propose that chronic pudendal neuromodulation (CPN) may be a useful treatment for PGAD symptoms. METHODS: A retrospective chart review was performed for women older than 18 years with a diagnosis of PGAD that had staged neuromodulation with placement of a tined lead at the pudendal nerve. Demographic, operative, and postoperative data were collected. A survey was then sent to these women to assess additional demographic data, preoperative and postoperative symptoms, and patient satisfaction. Descriptive statistics were performed. RESULTS: Six women underwent CPN for PGAD. Mean age was 52 (SD, 9) years. Five (83%) of 6 were still implanted at time of survey, at a mean of 38 months after implantation; 1 device was removed for nonuse. Four of 6 completed surveys and were still using their device. Three of 4 had met their treatment goals and were satisfied with CPN; 3 of 4 felt CPN was the most useful treatment modality they had used overall. Chronic pudendal neuromodulation also improved chronic pelvic pain (4/4), bowel function (3/4), and bladder function (3/4). CONCLUSIONS: Chronic pudendal neuromodulation can be an effective treatment for decreasing frequency of PGAD symptoms and providing symptom relief.

Radiographic Misdiagnoses After Periurethral Bulking Agents.

OBJECTIVES: Injectable urethral bulking agents are commonly used to manage stress urinary incontinence. Urologic or other symptoms may prompt pelvic imaging at a later date, when bulking agents may be visualized and incorrectly interpreted. Our goal was to evaluate the incidence of misdiagnosis and which pathologies were the most common misinterpretations and their frequency. METHODS: All records were reviewed for patients who underwent periurethral injection for stress urinary incontinence for pelvic imaging after treatment from 2005 to 2015. Radiological reports were reviewed for any description potentially related to injection therapy, and descriptive statistics performed. RESULTS: A total of 528 patients underwent injection of a urethral bulking agent. Of these, 79 patients (15%) had a total of 111 additional abdominal or pelvic imaging studies performed with abnormal periurethral findings mentioned. Thirty-nine (35%) of 111 studies were correctly interpreted as urethral bulking agents, and in 72 (65%) of 111 studies, the urethral bulking agents were not correctly identified. The most common misdiagnoses were bladder calcification (26; 23%), urethral diverticulum with stone (12; 11%), periurethral calcification (9; 8%), unknown pelvic density (8; 7%), and mass suspicious for malignancy (6; 5%). CONCLUSIONS: Urethral bulking agents commonly were not mentioned on subsequent imaging but, when commented on, were misinterpreted 65% of the time including worrisome pathologies (diverticulum with stone, unknown mass, and malignancy), requiring subsequent evaluation and potentially procedural/surgical management. It is critical for the ordering clinician to inform the radiologist of this history and for radiologists to consider bulking agents in the differential diagnosis of radiographic findings in this location.

Outcomes of Sacral Neuromodulation in Patients with Prior Surgical Treatment of Stress Urinary Incontinence and Pelvic Organ Prolapse.

OBJECTIVES: The aim of this study was to evaluate the efficacy of sacral neuromodulation in patients with prior stress urinary incontinence (SUI) or pelvic organ prolapse (POP) surgery. METHODS: Women in our prospective neuromodulation database were evaluated. Patients with a history of prior SUI/POP surgery were compared to those without. Medical records at baseline were reviewed, and primary outcome was defined as moderate/marked improvement on Global Response Assessment (GRA) at 3 months. Secondary outcomes were measured using bladder diaries and Overactive Bladder Symptom Severity (OABq-SS)/health-related quality of life (HRQOL). Data were analyzed with Pearson χ test, Fisher exact test, Wilcoxon rank-sum test, and repeated-measures analyses. RESULTS: Of 210 subjects, 108 (51%) had prior SUI/POP surgery. Patients with SUI/POP surgery had more prior hysterectomies. At 3 months, there was no difference between groups on GRA outcomes. On the bladder diary, both groups had improvement in median voids per 24 hours, urgency severity, and urge incontinence over 2 years. On the GRA, fewer patients in the SUI/POP group were treatment responders at 12 and 24 months. For urinary urgency, a few in this group were moderately/markedly improved at 6 months, and a higher proportion are reported still leaking urine at 6 and 12 months. Similar proportions in each group reported moderate/marked improvement in leaking. Satisfaction was similar between groups. The OABq-SS/HRQOL scores improved, and there was no difference between the groups. CONCLUSION: Sacral neuromodulation improves bladder symptoms in women with prior SUI/POP surgery, but response may be slightly less in those with prior surgery due to underlying bladder or pelvic floor issues.

The impact of prior back surgery on neuromodulation outcomes: A review of over 500 patients.

AIMS: To evaluate neuromodulation outcomes in patients with prior back surgery. METHODS: Adults in our prospective observational sacral/pudendal neuromodulation study were retrospectively evaluated. History and operative details were reviewed, and outcomes were measured at 3, 6, 12, and 24 months with overactive bladder questionnaire (OAB q) symptom severity (SS)/health related quality of life (HRQOL), interstitial cystitis symptom/problem indices (ICSI - PI), voiding diaries, and global response assessments (GRA). Data were examined with Pearson's χ2 , Fisher's exact, Wilcoxon rank sum tests, and logistic regression multivariate analysis. RESULTS: Five hundred and sixty patients were evaluated (mean age 58.8 ± 17 years; 83% female; 79% had a sacral lead placed), 109 (19%) had history of back surgery; 66 surgeries were lumbar. Back surgery patients were older (mean 63 ± 15 vs. 58 ± 17 years; P = 0.003) and a higher proportion had urge urinary incontinence (UUI) (64% vs. 50% P = 0.008). Generator implant rates were similar (94% vs. 91%; P = 0.34). OABq-SS and HRQOL and ICSI - PI composite scores did not differ between groups at any time point. On bladder diaries, median incontinence episodes daily at baseline and between stages were worse in the prior back surgery group but all bladder diary parameters improved significantly in both groups with the exception of mean voided volume which only improved significantly in the non-back surgery group. Most patients in both groups reported moderate/marked improvement in overall bladder symptoms. CONCLUSIONS: This study suggests that prior back surgery does not appear to impact clinical outcomes; therefore, neuromodulation may be offered in this patient population.

Pelvic Prolapse Repair in the Era of Mesh.

Pelvic organ prolapse repair with mesh remains the gold standard for advanced prolapse. There are several surgical approaches available to the pelvic reconstructive surgeon. Prolapse repair can be performed vaginally or abdominally using native tissue or may be augmented with a biologic or mesh patch. In this article, we will review the different approaches to prolapse repair, the role of mesh, and the risks and benefits of each option. Patient selection, surgical technique, and the rationale for using mesh will be explored. Complications from prolapse repair with mesh including dyspareunia, pelvic pain, mesh exposure, and reoperation will be discussed.

A multidisciplinary approach to the evaluation and management of interstitial cystitis/bladder pain syndrome: an ideal model of care.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a complex syndrome that has long been treated with bladder directed therapies, which often fail to address the multiple underlying etiologies that can contribute to this disease process. This disease often involves symptoms that extend beyond the bladder and involve the pelvic floor making it crucial for clinicians to approach the patient using a multidisciplinary team. This article will discuss the underlying etiologies for IC/BPS and describe the multidisciplinary approach which we have found to be extremely successful in managing this patient population.

Positive correlation between PEDF expression levels and macrophage density in the human prostate.

BACKGROUND: In this study, we investigated the capacity of pigment epithelium-derived factor (PEDF) to modulate the recruitment and the differentiation of monocytes/macrophages both in vitro and in human prostate. METHODS: Using Boyden chambers, we assessed PEDF effect on the migration of monocytes and chemically activated RAW 264.7 macrophages. Normal, prostatitis, and prostate cancer specimens were retrospectively selected and examined by immunohistochemistry for PEDF expression and infiltration of immune CD68 + macrophagic cells. PEDF expression and macrophage density were then correlated with each other and clinicopathological parameters. M1 and M2 differentiation markers were quantified by qRT-PCR, Western blotting, and ELISA. RESULTS: In chemotaxis, PEDF induced the migration of monocytes/macrophages. In immunohistochemistry, macrophages were markedly increased in prostatitis and malignant compared to normal tissues. PEDF was expressed at variable levels in the stroma and epithelium. PEDF mRNA was down-regulated in both prostate cancer and prostatitis compared to normal tissues. In correlation studies, macrophage density and PEDF expression were respectively positively and negatively associated with prostate size. Most importantly, PEDF expression positively correlated with macrophage density. Finally, PEDF stimulated the expression of iNOS, IL12, and TNFα; and inhibited IL10 and arginase 1 in mouse and human macrophages confirming a M1-type differentiation. CONCLUSIONS: Our data demonstrate that PEDF acts directly on monocytes/macrophages by inducing their migration and differentiation into M1-type cells. These findings suggest a possible role of macrophages in PEDF anti-tumor properties and may support further development of PEDF-based anti-cancer therapy.