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CRISPR/Cas9-based genome-editing therapies are poised to change the clinical outcome for many diseases with validated therapeutic targets awaiting an appropriate delivery system. Recent advances in lipid nanoparticle (LNP) technology make them an attractive platform for the delivery of various forms of CRISPR/Cas9, including the efficient and transient Cas9/gRNA ribonucleoprotein (RNP) complexes. In this study, we initially tested our novel LNP platform by delivering pre-complexed RNPs and template DNA to cultured mouse cortical neurons, and obtained successful ex vivo genome editing. We then directly injected LNP-packaged RNPs and DNA template into the mouse cornea to evaluate in vivo delivery. For the first time, we demonstrated wide-spread genome editing in the cornea using our LNP-RNPs. The ability of our LNPs to transfect the cornea highlights the potential of our novel delivery platform to be used in CRISPR/Cas9-based genome editing therapies of corneal diseases.

The objective was to investigate the impact of mindfulness-based stress reduction therapy on the urinary microbiome of patients with interstitial cystitis/bladder pain syndrome. In this Institutional Review Board-approved prospective cohort study, patients with interstitial cystitis/bladder pain syndrome were recruited to attend an 8-week mindfulness-based stress reduction course involving yoga and meditation. Eligible participants were English-speaking women aged 18 or older with interstitial cystitis/bladder pain syndrome. All participants had a negative urinalysis within 2 months of enrollment and were currently undergoing first- or second-line treatment at the time of recruitment. The mindfulness-based stress reduction course met weekly for 1 h. A straight-catheter urine sample was obtained prior to and following the mindfulness-based stress reduction series. DNA from urine samples underwent bacterial 16S ribosomal gene sequencing at Johns Hopkins University Laboratories followed by taxonomic abundance and diversity analysis by Resphera Biosciences Laboratory. Participants completed validated symptom questionnaires pre- and post-intervention. A total of 12 participants completed the 8-week course and were included in the analysis. The average age was 59 and the majority identified as white. Patient symptoms, measured by the Urogenital Distress Inventory Short Form and Interstitial Cystitis Symptom and Pain Indices, improved significantly (all p

To describe the impact of native tissue vaginal reconstruction on pelvic anatomy using dynamic magnetic resonance imaging. This prospective single-cohort observational study involved women undergoing native tissue reconstruction with intraperitoneal vaginal vault suspension for pelvic organ prolapse. Concomitant procedures such as hysterectomy, midurethral sling, and anterior or posterior colporrhaphy were allowed. Enrolled participants underwent dynamic pelvic imaging pre- and postoperatively. Radiographic and anatomic measurements were compared. Secondary outcomes included validated patient questionnaires. Fourteen participants were included in the analysis. The mean age was 62 years; all participants were Caucasian. Most participants had stage III pelvic organ prolapse. Significant improvements were noted in several radiographic measurements. The average H-line (representing levator hiatus width) with straining maneuvers improved following surgery (7.2 cm preoperatively vs. 6.6 cm postoperatively, p = 0.015). The average M-line (representing levator muscular descent) improved significantly with both straining (4.0 cm preoperatively vs. 3.0 cm postoperatively, p

OBJECTIVE The American College of Obstetricians and Gynecologists does not provide a recommendation regarding the preferred vaginal preparation solution. We intended to compare the effectiveness of chlorhexidine versus iodine in decreasing vaginal bacterial counts. METHODS In this institutional review board-approved study, participants undergoing total hysterectomy via vaginal or laparoscopic approach were randomized to 4% chlorhexidine or 10% iodine for presurgical vaginal preparation. Swabs were collected from the vaginal mucosa before, then 30, 60, and 90 minutes after preparation. Our primary outcome was the number of positive cultures (≥5,000 bacteria) at 90 minutes. The secondary outcomes included the presence of selected pathogens, postoperative complications, and infections. The sample size of 71 per arm was calculated using P = 0.05, 80% power, and anticipating a 22% difference in positive cultures. RESULTS Between May 2018 and August 2019, 85 participants were randomized. The average age was 59.8 years (SD, 11.4), and the median Charlson Comorbidity Index score was 2 (minimum, 0; maximum, 6). Baseline bacterial counts were similar in both groups. Chlorhexidine demonstrated a lower percentage of positive cultures at 90 minutes (47.6% vs 85.4%; odds ratio, 10.6; P = 0.001). In addition, the median bacterial count in the chlorhexidine group was significantly lower than the iodine group (3,000 vs 24,000 colony-forming units, P < 0.001) at 90 minutes. No surgical site infections were identified in either group during the 30-day postoperative period, and there were no reported adverse reactions to either solution. CONCLUSIONS Chlorhexidine resulted in substantially lower bacterial counts after preparation compared with iodine. Gynecologic surgeons may consider switching to 4% chlorhexidine for vaginal preparation before hysterectomy.

To describe associations between postoperative genital hiatus (GH) measurements and long-term anatomical and subjective outcomes following pelvic reconstructive surgery involving apical suspension. This IRB-approved secondary analysis reports outcomes 3–7 years following robotic sacrocolpopexy (RSC) and uterosacral ligament suspension (USLS). Objective and subjective measures were obtained through clinical examinations and validated questionnaires. Subjective success was defined as the absence of a symptomatic bulge or retreatment. Objective success was defined as all Pelvic Organ Prolapse Quantification (POP-Q) points at or above −1 at the long-term examination. Postoperative GH measures were obtained at 6 weeks (early) and 3–7 years (long term) postoperatively. GH measurements were classified as either normal (

To evaluate whether self-discontinuation of a transurethral catheter is noninferior to office discontinuation in patients requiring indwelling catheterization for postoperative urinary retention after pelvic reconstructive surgery.In this randomized noninferiority trial, patients with postoperative urinary retention after pelvic reconstructive surgery were assigned to self-discontinuation or office discontinuation of their catheter 1 week after surgery. The primary outcome was a noninferiority comparison of postoperative urinary retention at 1 week. Self-discontinuation patients were instructed on home catheter removal on postoperative day 7. Office discontinuation patients underwent a standard voiding trial on postoperative day 6-8. Postoperative urinary retention at 1 week was defined as continued catheterization on postoperative day 6-8. Secondary outcomes included urinary tract infections (UTI), residual volume at 2 weeks, duration of catheter use, recurrent postoperative urinary retention, number of patient encounters, and visual analog scales (VAS) regarding patient experience. Given a known incidence of postoperative urinary retention at 1 week (16%) and 15% noninferiority margin, a sample size of 74 per group (n=148) was planned.From January 2017 through March 2019, 217 women were screened and 157 were analyzed: 78 self-discontinuation and 79 office discontinuation. Demographic characteristics and surgeries performed were similar. Eleven patients in each group experienced postoperative urinary retention at 1 week (14.1% self-discontinuation vs 13.9% office discontinuation, P=.97), establishing noninferiority (difference 0.2%, 95% CI: -1.00, 0.10). There were significantly fewer patient encounters with self-discontinuation (42/78, 53.8% vs 79/79, 100%). Self-discontinuation patients demonstrated better VAS scores regarding pain, ease, disruption, and likelihood to use the same method again (all P.05). Though the rate of UTI was high, there was no difference between groups (59.0% self-discontinuation vs 66.7% office discontinuation, P=.32). Residual volume at 2 weeks, recurrent postoperative urinary retention, and duration of catheter use were also similar.Self-discontinuation of a transurethral catheter was noninferior to office-based discontinuation in the setting of postoperative urinary retention after pelvic reconstructive surgery. Self-discontinuation resulted in fewer patient encounters and improved patient experience.ClinicalTrials.gov, NCT02996968.

OBJECTIVE This study was conducted to assess the utility of a mirror in improving pain and vulnerability during a pelvic examination. METHODS In this prospective, institutional review board-approved, 2-cohort trial, all "new" patients presenting to a urogynecology office were offered to have a mirror or no-mirror present during their pelvic examination. Patients completed 100-mm visual analog scales regarding pain, anxiety, knowledge, control, embarrassment, and vulnerability before and after examination. The primary outcome was difference in level of pain and vulnerability between groups. Secondary outcomes included comparisons from baseline to postexamination scores within groups, patient satisfaction, and examination duration. A sample size of 68 participants in each arm was planned. RESULTS From April 2019 to May 2020, 147 participants were enrolled. Two participants were excluded, 145 were included in the final analysis; 74 in the no-mirror group and 71 in the mirror group. The average age was 55.9 (±13) years, and the groups were overall similar. There was no difference in primary outcomes of pain or vulnerability, but the mirror group showed improved levels of control (P = 0.006) and knowledge (P = 0.018) following examination. All participants reported high satisfaction, and those that selected a mirror reported strong preference for future use. CONCLUSIONS Patients who chose to use the mirror did not demonstrate a difference in pain or vulnerability scores; however, they exhibited benefit to their sense of control and knowledge after the pelvic examination. Although the mirror did not benefit all patients, this is a simple option that could improve the examination experience for some.Clinical Trial Registration:ClinicalTrials.gov, NCT03785548.

BACKGROUND The number of male medical students selecting Obstetrics and Gynecology (OBGYN) has declined in recent years. However, it is unclear whether patients prioritize a female provider. The aim of the study was to assess gender preferences amongst female patients regarding their OBGYN and other medical providers. A secondary aim was to evaluate qualities that are important to female patients regarding their OBGYN. METHODS This was a USA cross-sectional survey using an internet-based provider (SurveyMonkey®) in January 2019. A 19-item questionnaire was distributed to females aged 18-80. The survey queried demographics, gender preferences for medical providers and important qualities in selecting their OBGYN. A goal of 1000 responses was determined for the study. RESULTS One thousand and fifteen women completed the entire survey. Sixty-six percent of respondents (N.=667) preferred a female OBGYN, while 8% (N.=87) preferred male, 25% (N.=261) no preference. The majority (51%) voiced no gender preference regarding other providers (N.=521). When asked to rank the 3 most important qualities in selecting their OBGYN, experience (57%), knowledge (51%), reputation (35%) and personality (34%) were most frequently chosen amongst the top 3. Gender was listed among the 3 important qualities by only 8% (N.=88). Women who identified as single

To describe national practice patterns regarding apical support procedures at time of hysterectomy for prolapse prior to the American College of Obstetricians and Gynecologists (ACOG) 2017 Practice Bulletin on pelvic organ prolapse. This retrospective descriptive study analyzed 24 months of data from the National Surgical Quality Improvement Program (NSQIP) database, from 2015 and 2016. Patients undergoing hysterectomy for the indication of pelvic organ prolapse were included. Surgical details, diagnostic codes, subspecialty, patient demographics, and postoperative complications were collected. Comparisons were conducted between those who did and did not undergo apical support procedures. Further comparisons, including logistic regressions, were performed using subspecialty designation. During the study period, 3458 hysterectomies were performed for the indication of pelvic organ prolapse. Of this population, 76% were White, with an average age of 61 years, BMI of 27.6, and parity of 2, and 90.5% carried the diagnosis of apical prolapse. Slightly over half (51.8%) had a concurrent procedure to support the vaginal apex. When performed by Female Pelvic Medicine and Reconstructive Surgery (FPMRS) physicians, 65.7% underwent an apical suspension at time of hysterectomy for prolapse compared with 40.2% of non-FPMRS (p

Background Improving the patient experience, controlling pain with non-opiate therapies, and preparing for value based reimbursement are increasingly important foci for both physicians and hospitals. Objectives We sought to determine if the addition of music and a natural landscape image to postoperative hospital rooms would result in improved pain and satisfaction scores among inpatients undergoing pelvic reconstructive surgery. Study Design This was an Institutional Review Board approved, randomized controlled trial. Eligible candidates were 18-85 years old, English speaking, and scheduled to undergo native tissue vaginal vault suspension for symptomatic pelvic organ prolapse. Exclusions included history of a chronic pain or substance abuse. Subjects were advised the purpose of the study was to assess the impact of changes to the hospital environment on patient experience, but were blinded to their group and intervention details. Changes included a landscape image mounted to the wall, as well as access to a speaker with preprogrammed music selections. The intervention group was instructed to listen to their preferred music for a minimum of two 30-minute sessions postoperatively. The control group had a standard hospital room, without music or landscape. All patient rooms were private. The primary outcome was the Visual Analogue Scale (VAS) for pain on the morning of post-operative day one. Secondary outcomes included narcotic use, likelihood to refer family to the same hospital facility, satisfaction with care and the hospital, and perception of a healing environment. A sample size of 43 subjects per arm was calculated in order to detect a difference of 10mm in VAS pain score. Results One hundred thirty-three subjects were enrolled; primary outcome data was available for 92 (46 per arm). The mean age was 63.8 (SD 9.5) years, median Charlson Comorbidity score was 2 (min=0,max=7), and 94.6% were Caucasian. On postoperative day one, median VAS scores for pain were low (28.8mm (0,86), 24.5mm (0,81)), and did not differ between intervention and control, respectively (p=0.57). Total morphine equivalents (p=0.817) and nursing pain scores (p=0.774) were also similar. However, the intervention group displayed a higher likelihood to refer family members to the hospital (98mm(47, 100), 96mm(65, 100), p=0.037). At 2 weeks postoperative, the intervention group demonstrated higher satisfaction with their care (98mm (34, 100), 95mm (42, 100), p=0.032), the hospital (98mm (71, 100), 94mm (6, 100), p=0.004), and the healing environment provided during their stay (98mm (52, 100), 92mm (19, 100), p=0.020), than those in standard hospital rooms. Conclusion In this randomized trial, we demonstrated music and landscape imagery did not significantly impact post-operative pain scores, however they had a positive impact on the postoperative experience. Further, this impact appeared to broaden two weeks following surgery. Given the importance of value-based care, interventions such as these should be emphasized in an effort to enhance patient satisfaction, quality scores and overall well-being.