PKCµ promotes keratinocyte cell migration through Cx43 phosphorylation-mediated suppression of intercellular communication.

Downregulation of intercellular communication through suppression of gap junctional conductance is necessary during wound healing. Connexin 43 (Cx43), a prominent gap junction protein in skin, is downregulated following wounding to restrict communication between keratinocytes. Previous studies found that PKCµ, a novel PKC isozyme, regulates efficient cutaneous wound healing. However, the molecular mechanism by which PKCµ regulates wound healing remains unknown. We have identified that PKCµ suppresses intercellular communication and enhances cell migration in an in vitro wound healing model by regulating Cx43 containing gap junctions. PKCµ can directly interact with and phosphorylate Cx43 at S368, which leads to Cx43 internalization and downregulation. Finally, utilizing phosphomimetic and non-phosphorylatable S368 substitutions and gap junction inhibitors, we confirmed that PKCµ regulates intercellular communication and in vitro wound healing by controlling Cx43-S368 phosphorylation. These results define PKCµ as a critical regulator of Cx43 phosphorylation to control cell migration and wound healing in keratinocytes.

Patient experiences following prolapse surgery implementing a same-day discharge model: a prospective study.

INTRODUCTION AND HYPOTHESIS: Previous research has not evaluated patient experiences following vaginal reconstructive surgery using a same-day discharge model. The objective of this study was to describe patient experiences following major vaginal reconstructive surgery and same-day discharge. METHODS: In this descriptive study, patients undergoing vaginal hysterectomy with pelvic reconstruction were preoperatively enrolled. Questionnaires detailing experience with same-day discharge, surgical recovery, and advice for prospective patients were completed. Our primary outcome was question 7 of the Surgical Satisfaction Questionnaire: Looking back, if you "had to do it all over again" would you have the surgery again? Descriptive statistics were performed, and correlations were performed with Spearman's rank test. RESULTS: Sixty patients were enrolled; 54 underwent surgery. Eighty-seven percent of patients completed the 12-week questionnaire. At 12 weeks, 96% of patients (n = 45) would have the surgery again, and 91% (n = 42) were satisfied with the results of surgery. Twelve weeks postoperatively, the most common patient-reported complications were urinary tract infection (n = 8, 17%), catheter concerns (n = 5, 11%), and constipation (n = 5, 11%). When asked to list the best parts of their surgical experience, half of patients felt that this was the office staff or physician themselves (n = 24, 51%). When asked what advice they would provide to future patients, the most common responses included having a support person at home and taking time for recovery. CONCLUSIONS: In this sample of women receiving same-day discharge following vaginal hysterectomy with pelvic reconstruction, we present a unique insight into the most common patient concerns postoperatively. Rates of satisfaction and comfort were high.

Intrarectal diazepam following pelvic reconstructive surgery: a double-blind, randomized placebo-controlled trial.

BACKGROUND: Patients undergoing vaginal hysterectomy with native tissue pelvic reconstruction typically have low pain levels overall in the postoperative period. Notwithstanding, pain control immediately after surgery may be more challenging and a barrier to same-day discharge. Intrarectal diazepam has been used for acute and chronic pelvic pain and has a pharmacokinetic profile ideal for intermittent use. However, its use has not been investigated after the surgical intervention. OBJECTIVE: This study aimed to evaluate the effect of diazepam rectal suppositories on early postoperative pain after hysterectomy and vaginal reconstruction for pelvic organ prolapse. STUDY DESIGN: This was a double-blind, randomized, placebo-controlled trial comparing postoperative pain scores after vaginal hysterectomy with native tissue prolapse repairs. Patients were randomized to receive either an intrarectal 10-mg diazepam suppository or an identical placebo. Moreover, the participants completed the questionnaires at baseline, the morning of postoperative day 1, and 2 weeks after the operation. Surveys included visual analog scales for pain, a validated Surgical Satisfaction Questionnaire, and queries regarding medication side effects and postoperative recovery. The primary outcome was pain scores based on a visual analog scale approximately 3 hours after surgery. The secondary outcomes included total morphine equivalents after surgery, patient satisfaction with pain control, same-day discharge outcome, and overall satisfaction. The chi-square, Fisher exact, and Mann-Whitney tests were used. Based on a 10-mm difference in postoperative vaginal pain using the visual analog scale, sample size was calculated to be 55 patients in each arm to achieve 80% power with an alpha of.05. RESULTS: From February 2020 to August 2021, 130 participants were randomized. Of those participants, 7 withdrew, and 123 were analyzed: 60 in the diazepam group and 63 in the placebo group. The median age was 65 years (interquartile range, 27-80), the median body mass index was 27.9 kg/m2 (interquartile range, 18.70-45.90), and 119 of 123 participants (96.7%) were White. There was no difference in the baseline characteristics, prolapse stage, or types of procedures performed between groups. Most participants had concurrent uterosacral ligament suspension with anterior and posterior repairs. Of note, 50 of 123 participants (41%) had midurethral slings. Moreover, 61 of 123 participants (50%) were discharged on the day of surgery. There was no difference in the primary outcome of vaginal pain 3.5 to 6.0 hours postoperatively (25 vs 21 mm; P=.285). In addition, the amount of rescue narcotics used in the immediate postoperative period (19.0 vs 17.0 MME; P=.202) did not differ between groups. At 2-weeks postoperatively, patients in the placebo group reported higher satisfaction with pain control in the hospital (31 vs 43 mm; P=.006) and pain control at home (31 vs 42 mm; P=.022). No difference was noted between same-day discharges and those who were admitted overnight. CONCLUSION: The placement of a 10-mg diazepam rectal suppository immediately after pelvic reconstructive surgery did not improve pain or narcotic usage in the early postoperative period. Although the placebo group reported slightly higher satisfaction with pain control 2 weeks after surgery, overall pain levels were low. Therefore, we do not believe that the addition of diazepam to the postoperative regimen is warranted.

Methenamine Hippurate With Cranberry Capsules Versus Cranberry Alone for Urinary Tract Infection Prevention in a Short-Term Indwelling Foley Catheter Population After Urogynecologic Surgery: A Double-Blinded Randomized Controlled Trial.

IMPORTANCE: There is little consensus on an effective nonantibiotic agent for the prevention of urinary tract infection (UTI) after pelvic reconstructive surgery. OBJECTIVE: The aim of the study was to investigate the impact of methenamine hippurate with cranberry capsules on rates of UTI after pelvic reconstructive surgery, among patients requiring short-term catheterization. STUDY DESIGN: In this randomized, double-blinded placebo-controlled trial, patients discharged with a catheter after pelvic reconstructive surgery were approached to participate. Participants were randomized to receive cranberry with methenamine or cranberry with placebo. Primary outcome was number of UTIs treated within 1 week after surgery. Secondary outcomes included incidence of UTIs treated within 6 weeks postoperatively, bacterial species on culture, urinary pH, catheter duration, patient adherence, and satisfaction. A sample size of 88 participants per arm was planned. RESULTS: From June 2019 to July 2021, 185 patients were randomized and 182 analyzed; 89 received placebo and 93 received methenamine. Both groups were similar. Incidence of UTI at 1 week was significantly higher in the placebo group (79.8%) compared with the methenamine group (66.7%; odds ratio, 1.97; 95% confidence interval, 1.01-3.87; P = 0.048). This difference increased by 6 weeks postoperatively (89.9% vs 72.0%; odds ratio, 3.45; 95% confidence interval, 1.51-7.87; P = 0.003). There were fewer pseudomonal UTIs in the methenamine group (P = 0.041). Duration of catheterization and urinary pH were similar. Overall adherence and level of satisfaction was high. CONCLUSIONS: In this high-risk population, methenamine was well tolerated and significantly reduced UTI rates. Methenamine with cranberry should be considered as an effective prophylactic therapy to reduce this common complication after pelvic surgery.

Clinical Benefit of Routine Postoperative Hemoglobin Testing After Vaginal Hysterectomy and Reconstruction for Symptomatic Pelvic Organ Prolapse.

OBJECTIVES: The objective of this study was to determine the clinical benefit of a routine complete blood count (CBC) on the first postoperative day after vaginal hysterectomy with reconstruction. METHODS: This retrospective cohort study evaluated patients undergoing vaginal hysterectomy with native tissue prolapse repair between 2014 and 2019. Baseline and operative data, preoperative and postoperative blood counts, signs of anemia, and complications were recorded. Objective signs of anemia included tachycardia, hypotension, and low urine output. Subjective signs of anemia included dizziness, weakness, pallor, and diaphoresis. Complications, such as blood transfusions, additional testing, and readmission, were recorded. RESULTS: Five hundred and seventy patients had a postoperative CBC. The median preoperative hemoglobin level was 13.5 g/dL (min, 9.4; max, 16.9). Ninety-seven (17%) patients had a postoperative hemoglobin of 10 g/dL or less, with a median hemoglobin of 11.2 g/dL (min, 5.6; max, 14.9). Signs of anemia occurred in 72 (12.6%) patients: 64 (11.2%) showing objective signs, 13 (2.3%) reporting subjective symptoms, and 5 (0.8%) noting both. The most common objective sign was hypotension (n = 40; 63.5%). Five women received transfusions (0.9%). All patients receiving a blood transfusion showed objective signs of anemia; 3 (50%) patients had objective and subjective signs. Twenty-one (3.7%) patients had more than 1 CBC test during admission; 9 (42.9%) of these women were asymptomatic and had no further intervention. There were no readmissions related to postoperative anemia. CONCLUSIONS: Patients that require intervention for anemia after vaginal hysterectomy and reconstruction will manifest clinical signs or symptoms. Routine CBC testing in this cohort did not provide benefit and led to superfluous procedures in the vast majority of participants.

Chlorhexidine Versus Iodine for Vaginal Preparation Before Hysterectomy: A Randomized Clinical Trial.

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 ɑP = 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.

Routine Office Assessment After OnabotulinumtoxinA Injection for Overactive Bladder Is Unnecessary to Detect Clinically Significant Voiding Dysfunction.

OBJECTIVE: This study aimed to determine if routine assessment of patients after onabotulinumtoxinA injections for overactive bladder is necessary to detect clinically significant voiding dysfunction. METHODS: This retrospective cross-sectional cohort study analyzed patients who underwent intravesical injection of onabotulinumtoxinA for overactive bladder during a 4-year period. Patients were included for analysis if they returned for an office follow-up visit within 1 month of administration. Baseline demographic data; procedural details; postvoid residual volumes; abnormal postprocedure voiding symptoms, including urinary frequency, pain, or inability to void; urinary tract infections; and initiation of intermittent self-catheterization were recorded. Descriptive statistics, point-biserial and Pearson correlation analyses were performed. RESULTS: Two hundred thirty-seven injections were included in our analysis. Fifteen encounters, from 13 patients, required the initiation of intermittent self-catheterization (6.3%). The median postvoid residual in those treated with intermittent self-catheterization was 300 mL (min, max: 200, 750 mL); all had received 100 units of onabotulinumtoxinA. The most common symptom among those requiring intermittent self-catheterization was urgency (n = 13; 87%), whereas 93% (n = 14) had at least 1 bothersome symptom. Correlation analyses showed a weak positive correlation with elevated postvoid residual volume and a history of prolapse repair (r = 0.269, P = 0.004), and prior pelvic surgery (r = 0.205, P = 0.029). CONCLUSIONS: Clinically relevant urinary retention that required intermittent self-catheterization after onabotulinumtoxinA injection for overactive bladder occurred in 6.3% of participants in this sample. The vast majority of patients who required intermittent self-catheterization described symptoms that they were able to self-identify.

Utilization of a Mirror During Pelvic Examinations: Does it Improve the Patient's Experience?

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.

Benign Cysts of the Vulva and Vagina: A Comprehensive Review for the Gynecologic Surgeon.

IMPORTANCE: Gynecologists are experts in providing care to women with vulvovaginal complaints. Cysts located in the vagina and vulva can cause pain and irritation and incite concern. Given the relatively low prevalence of these cysts in the population, helpful diagnostic and management information for providers is scarce. OBJECTIVE: This article will detail the epidemiology, embryology, presentation, and management of vulvovaginal cysts. EVIDENCE ACQUISITION: We completed a comprehensive literature review for all available data and included case reports, case series, histological studies, and descriptive articles obtained from PubMed and relevant textbook chapters. RESULTS: In general, cystic lesions of the vagina and vulva are typically benign and asymptomatic and do not require intervention. Special attention should be paid to cysts arising in women older than 40 years and those that are fixed or associated with pain or bleeding. Cysts that require management may require imaging, often either with transvaginal ultrasound or magnetic resonance imaging. Surgical excision, when necessary, has a high success rate. CONCLUSIONS AND RELEVANCE: Vaginal and vulvar cysts have a myriad of presentations and etiologies. A thorough understanding of these is helpful to guide decisions about further testing and management options.

Crystal structure of the thermochromic bis-(di-ethyl-ammonium) tetra-chlorido-cuprate(II) complex.

In the structure of the title complex salt, (Et2NH2)2[CuCl4], the asymmetric unit consists of four unique di-ethyl-ammonium cations and three unique tetra-chlorido-cuprate anions. Two of the three anions are located with their copper atoms on independent crystallographic twofold axes, while the remaining tetra-chlorido-cuprate is located at a general position of the ortho-rhom-bic space group P21212. Two of the three Cu atoms adopt a distorted square-planar/disphenoidal geometry and the third Cu atom has a regular square-planar coordination environment. The di-ethyl-ammonium cations form an extensive hydrogen-bonded network through N-H⋯Cl inter-actions with the tetra-chlorido-cuprate anions, resulting in a two-dimensional sheet-like hydrogen-bonded network parallel to the ab direction. The complex was observed to undergo a color shift from deep green at room temperature to pale yellow at temperatures above 328 K.