Temporal dynamics of certain human microbiotas have been described in longitudinal studies; variability often relates to modifiable factors or behaviors. Early studies of the urinary microbiota preferentially used samples obtained by transurethral catheterization to minimize vulvovaginal microbial contributions. Whereas voided specimens are preferred for longitudinal studies, the few studies that reported longitudinal data were limited to women with lower urinary tract (LUT) symptoms, due to ease of accessing a clinical population for sampling and the impracticality and risk of collecting repeated catheterized urine specimens in a nonclinical population. Here, we studied the microbiota of the LUT of nonsymptomatic, premenopausal women using midstream voided urine (MSU) specimens to investigate relationships between microbial dynamics and personal factors. Using 16S rRNA gene sequencing and a metaculturomics method called expanded quantitative urine culture (EQUC), we characterized the microbiotas of MSU and periurethral swab specimens collected daily for approximately 3 months from a small cohort of adult women. Participants were screened for eligibility, including the ability to self-collect paired urogenital specimens prior to enrollment. In this population, we found that measures of microbial dynamics related to specific participant-reported factors, particularly menstruation and vaginal intercourse. Further investigation of the trends revealed differences in the composition and diversity of LUT microbiotas within and across participants. These data, in combination with previous studies showing relationships between the LUT microbiota and LUT symptoms, suggest that personal factors relating to the genitourinary system may be an important consideration in the etiology, prevention, and/or treatment of LUT disorders. IMPORTANCE Following the discovery of the collective human urinary microbiota, important knowledge gaps remain, including the stability and variability of this microbial niche over time. Initial urinary studies preferentially utilized samples obtained by transurethral catheterization to minimize contributions from vulvovaginal microbes. However, catheterization has the potential to alter the urinary microbiota; therefore, voided specimens are preferred for longitudinal studies. In this report, we describe microbial findings obtained by daily assessment over 3 months in a small cohort of adult women. We found that, similarly to vaginal microbiotas, lower urinary tract (LUT) microbiotas are dynamic, with changes relating to several factors, particularly menstruation and vaginal intercourse. Our study results show that LUT microbiotas are both dynamic and resilient. They also offer novel opportunities to target LUT microbiotas by preventative or therapeutic means, through risk and/or protective factor modification.

Little is known about pediatric spinal cord high grade gliomas (SCHGG) beyond their dismal prognosis. Here, we analyzed the HIT-GBM(®) database for the influence of surgical resection on survival. Between 1991 and 2010 the HIT-GBM group collected data from European children diagnosed with high grade glioma. Patients with the following inclusion criteria were analyzed in this study: astrocytic histology, WHO grade III or IV, age at diagnosis <18 years, and tumor localized to the spinal cord. 28 patients (mean age 11.28 years, 14 male) with primary SCHGG were identified. The tumor sizes were measured by the span across adjacent vertebrae and varied greatly (range: 1-20, median: 4). Histology was classified as WHO grade III in 15 and grade IV in 13 tumors. Of note, the four largest tumors identified were WHO grade III. Surgery was classified as complete resection (n = 6), subtotal resection (STR) (n = 7), partial resection (n = 12) or biopsy only (n = 3). 27 patients received chemotherapy, 22 of which also received radiation. With the mean follow-up time of 2.88 (SD ± 2.95) years, 14 patients were still alive resulting in a median overall survival of 2.5 years (SE ± 1.6). The positive prognostic indicators for overall survival were: age younger than 5 years (P = 0.047), WHO grade III (P = 0.046), absence of necrosis (P = 0.025) and gross total resection (GTR) (P = 0.012). The prognosis of SCHGG might not be as miserable as generally assumed. GTR is of benefit. Larger data sets and meta-analysis are necessary to identify patient sub-groups.

We conducted a phase II study to test methotrexate (5 g/m(2)), as a single agent prior to radiochemotherapy for pediatric high-grade glioma and diffuse intrinsic pontine glioma. Thirty patients (19 male, median age 10.8) were enrolled. Tumors were located as follows: cortex 10, pons 7, other 13. Tumor resection was classified as gross total in 6, subtotal in 6, partial in 4, biopsy in 11 and not performed in 3. WHO grading of the histology was: IV: 11, III: 12 and II: 3. Patients received methotrexate 5 g/m(2) in 24-hour infusions on days 1 and 15. Subsequently 54 Gy radiation was administered with simultaneous chemotherapy including cisplatin, etoposide, vincristine and ifosfamide as previously described. Eight 6-weeks cycles of maintenance chemotherapy consisted of vincristine 1.5 mg/m(2) on days 1, 8 and 15; lomustine 100 mg/m(2) on day 2 and prednisone 40 mg/kg on days 1-17. Event-free survival rates in the whole group of 30 patients were: 43, 20, and 13% after 1, 2 and 5 years, respectively. The response evaluation after methotrexate was available in 19 of the 24 patients who started treatment with measurable disease: CR: 0, PR: 1, SD 18, PD: 0. After radiochemotherapy the response of 24 patients with measurable disease was CR: 1, PR 10, SD 12, PD 1. Both response and event-free survival were superior to the control group of 330 patients treated in various protocols of the same cooperative group. In subgroup analyses the use of dexamethasone during early treatment was linked to poor event free survival. Giving two cycles of high-dose methotrexate prior to radiochemotherapy was feasible, and the approach was taken forward to a randomized phase III trial.

In this retrospective analysis, the duration of use was longest with the Gellhorn pessary. Older age and vaginal estrogen use were associated with longer pessary use.

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245/250) 24MANUSCRIPT: (5000/5000) 25 ACKNOWLEDGMENTS: We thank Mary Tulke RN for her assistance with participant 35 recruitment. We also acknowledge funding from NIH (R01 DK104718 awarded to AJW 36and LB). The funders did not play a part in the design or conduct of the study. 37 TKP, BW, LB, ERM, and AJW designed the study. TKP and BW recruited participants. 38TKP processed the specimens. TH prepared them for DNA sequencing. RL sequenced 39 the specimens. TKP, BW, QD and AJW analyzed the data. TKP and AJW wrote the 40 manuscript. TKP, BW, TH, RL, LB, QD, ERM, and AJW reviewed and edited the 41 manuscript. 42 43 ABSTRACT 59Temporal dynamics of certain human microbiotas have been described in 60 longitudinal studies; variability often relates to modifiable factors or behaviors. Early 61 studies of the urinary microbiota preferentially used samples obtained by transurethral 62 catheterization to minimize vulvo-vaginal microbial contributions. Whereas voided 63 specimens are preferred for longitudinal studies, the few studies that reported 64 longitudinal data were limited to women with lower urinary tract (LUT) symptoms, due to 65 ease of accessing a clinical population for sampling and the impracticality and risk of 66 collecting repeated catheterized urine specimens in a non-clinical population. Here, we 67 studied the microbiota of the LUT of non-symptomatic, pre-menopausal women using 68 mid-stream voided urine (MSU) specimens to investigate relationships between 69 microbial dynamics and personal factors. Using 16S rRNA gene sequencing and a 70 metaculturomics method called Expanded Quantitative Urine Culture (EQUC), we 71 characterized the microbiotas of MSU and peri-urethral swab specimens collected daily 72 for approximately three months from a small cohort of adult women. Participants were 73 screened for eligibility, including ability to self-collect paired urogenital specimens prior 74 to enrollment. In this population, we found that measures of microbial dynamics related 75 to specific participant-reported factors, particularly menstruation and vaginal 76intercourse. Further investigation of the trends revealed differences in composition and 77 diversity of LUT microbiotas within and across participants. These data, in combination 78 with previous studies showing relationships between the LUT microbiota and LUT 79 symptoms, suggest that personal factors relating to the genitourinary system may be an 80 important consideration in the etiology, prevention, and/or treatment of LUT disorders.

Objective To correlate lower urinary tract symptoms typically associated with a urinary tract infection (UTI) with physical examination findings of pelvic floor myofascial pain (PFMP). Methods This retrospective review included all new patients presenting to a urogynecology clinic between August 2 and December 19, 2016. Patients completed validated questionnaires, had a catheterized urine specimen, and underwent pelvic examination. Associations between demographics, symptoms, urine culture, and PFMP were analyzed. Results We included 250 patients with urinary frequency (n=160, 64.0%), urgency (n=155, 62.0%), urgency incontinence (n=140, 56.0%), pelvic pain (n=43, 17.2%), and dysuria (n=25, 10.0%). PFMP was detected in 125 (50.0%) patients and culture‐proven UTI in 15 (6.0%) patients. Demographics associated with PFMP were lower prolapse stage (P<0.001), age younger than 50 years (P<0.001), lower parity (P=0.028), and non‐white ethnicity (P=0.003). Symptoms associated with PFMP were dysuria (adjusted odds ratio 4.13, 95% confidence interval 1.08–15.78), urgency/frequency (2.72, 1.47–5.04), and patient‐reported pelvic pain (2.57, 1.08–6.12). These symptoms were independent predictors in multivariable logistic regression analysis. Conclusions Most patients had symptoms associated with UTI; however, culture‐confirmed diagnosis was infrequent and PFMT was diagnosed in half of participants. Clinicians treating women with these symptoms are advised to examine the pelvic floor muscles.

Purpose:We compared urinary tract infection (UTI) symptom resolution rates at 7–10 days in symptomatic women randomized to treatment based on standard urine culture (SUC) versus expanded quantitative urine culture (EQUC) results.Materials and Methods:Women ≥18 years old who responded “yes” to “do you feel you have a UTI?” agreed to urethral catheterization and followup. Symptoms were assessed using the validated UTI Symptom Assessment (UTISA) questionnaire. Culture method was randomized 2:1 (SUC:EQUC); antibiotics were prescribed to women with positive cultures. The primary outcome, UTI symptom resolution, was determined 7–10 days following enrollment on all participants regardless of treatment.Results:Demographic data were similar between groups. Of the SUC and EQUC groups 63% and 74% had positive cultures (p=0.10), respectively. Of participants with positive cultures 97% received antibiotics. Primary outcome data were provided by 215 of 225 participants (SUC 143 [95%], EQUC 72 [97%]). At the primary outcome assessment, 64% and 69% in the SUC and EQUC groups, respectively, reported UTI symptom resolution (p=0.46); UTISA scores improved from baseline in the EQUC arm compared to the SUC arm (p=0.04). In the subset of women predominated by non-Escherichia coli (76), there was a trend toward more symptom resolution in the EQUC arm (21%, p=0.08).Conclusions:Symptom resolution was similar for the overall population (E. coli and non-E. coli) of women treated for UTI symptoms based on SUC or EQUC. Although the sample size limits conclusions regarding the utility of EQUC in women with non-E. coli uropathogens, the detected trend indicates that this understudied clinical subset warrants further study.