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Study Objective: To assess long-term urinary function for women having laparoscopic surgery for endometriosis., Design: Institutional Review Board-approved nested cohort study within a larger randomized controlled trial assessing urinary function following any benign laparoscopy for gynecological presentations., Setting: Two tertiary-level university-affiliated hospitals., Patients: Women with histologically confirmed endometriosis within the randomized controlled trial between April 2012 and November 2019, where baseline urinary function was determined., Interventions: Women with histologically confirmed endometriosis were contacted between February and October 2020, and urinary function was re-assessed., Measurements and Main Results: Urinary function was assessed using validated questionnaires across the domains of filling, voiding, incontinence, and quality of life determined distant from surgery. Higher scores correlated with a greater severity of symptoms. From 518/711 (72.9%) women with histologically confirmed endometriosis, 289/518 (55.8%) consented to the nested study. At a mean of 50 months (range 12-103 months) post-operatively, 35 participants (12.1%) had sought treatment for bladder symptoms, and 81 participants (28.0%) reported at least one urinary tract infection since their index surgery. There was a significant worsening of symptoms for filling, voiding, incontinence, and quality of life pre-operative to post-operatively (2.27 vs 3.32, 0.93 vs 2.02, 1.06 vs 2.32, 0.83 vs 2.13 respectively, p <.001). There was no statistically significant difference in urinary questionnaire scores in participants with and without uterovesical endometriosis. There was no statistically significant difference in any parameter when comparing any revised American Society of Reproductive Medicine (rASM) stage of endometriosis. Participants who had post-operative urinary retention reported a higher mean voiding score than those who did not (3.24 vs 1.94, p = .017), while participants with post-operative urinary tract infection reported a higher mean frequency score than those who did not (5.17 vs 3.24, p = .016)., Conclusion: This study suggests a decline in urinary function over time following laparoscopic surgery for endometriosis that is not dependent on the severity or location of the disease., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

Objective: No consensus currently exists regarding patient-reported outcome measure (PROM) instruments. This structured review was conducted to identify the PROMs used by randomized controlled trials (RCTs) that evaluated surgical treatment in patients with endometriosis., Data Sources: Two parallel searches were conducted by a medical librarian using Ovid MEDLINE, Ovid Embase, and Cochrane Library for RCTs published from 2000 to July 2022. One search focused on studies reporting quality of life (QoL), and the second search focused on studies reporting pain and sexual, bowel, and bladder function., Method of Study Selection: During the title and abstract screening and reference check, 600 results were identified on PROMs relating to QoL and 465 studies on PROMs relating to pain and sexual, bowel, and/or bladder function and an evaluation of 17 and 12 studies conducted, respectively. The inclusion criteria involved selecting RCTs that focused on surgical intervention and assessing QoL, pain, and sexual, bowel, and/or bladder function using PROMs., Tabulation, Integration, and Results: Covidence software was used to organize and identify duplicate articles through screening. We developed a data extraction form to collect key information about each included study, as well as the pertinent PROMs used in the study. Assessment of the risk of bias of each study was also performed. A total of 19 studies were identified involving 2089 participants and a total of 16 PROMs used across the studies; 9 of 19 studies (47%) were rated as having a low risk of bias. There were no high-risk studies identified in this review., Conclusion: This study identified a large number of RCTs in surgical treatment of endometriosis that used various PROMs to assess QoL, pain, and bladder, bowel, and sexual function. The PROMs used by high-quality RCTs for QoL include Endometriosis Health Profile-30, Endometriosis Health Profile-5, Short-Form 36, Short-Form 12, and EQ-5D; for bowel-related symptoms Knowles-Eccersley-Scott-Symptom Questionnaire, Gastrointestinal Quality of Life Index, and Cleveland Clinic Fecal Incontinence Severity Scoring System/Wexner; for bladder-related function Bristol Female Lower Urinary Tract Symptoms, International Prostate Symptom Score, Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire, and Urinary Symptom Profile; and finally for sexual function Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire and Sexual Activity Questionnaire. Unlike other domains, only one tool (visual analog scale) was the dominant PROM used for the assessment of pain. In addition, the use of more than one PROM in each study to assess different aspects of patient's health and pain symptoms did not become prevalent until after 2015., (Copyright © 2023. Published by Elsevier Inc.)

Background: In sepsis and acute respiratory distress syndrome (ARDS), heterogeneity has contributed to difficulty identifying effective pharmacotherapies. In ARDS, two molecular phenotypes (hypoinflammatory and hyperinflammatory) have consistently been identified, with divergent outcomes and treatment responses. In this study, we sought to derive molecular phenotypes in critically ill adults with sepsis, determine their overlap with previous ARDS phenotypes, and evaluate whether they respond differently to treatment in completed sepsis trials., Methods: We used clinical data and plasma biomarkers from two prospective sepsis cohorts, the Validating Acute Lung Injury biomarkers for Diagnosis (VALID) study (N=1140) and the Early Assessment of Renal and Lung Injury (EARLI) study (N=818), in latent class analysis (LCA) to identify the optimal number of classes in each cohort independently. We used validated models trained to classify ARDS phenotypes to evaluate concordance of sepsis and ARDS phenotypes. We applied these models retrospectively to the previously published Prospective Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis and Septic Shock (PROWESS-SHOCK) trial and Vasopressin and Septic Shock Trial (VASST) to assign phenotypes and evaluate heterogeneity of treatment effect., Findings: A two-class model best fit both VALID and EARLI (p<0·0001). In VALID, 804 (70·5%) of the 1140 patients were classified as hypoinflammatory and 336 (29·5%) as hyperinflammatory; in EARLI, 530 (64·8%) of 818 were hypoinflammatory and 288 (35·2%) hyperinflammatory. We observed higher plasma pro-inflammatory cytokines, more vasopressor use, more bacteraemia, lower protein C, and higher mortality in the hyperinflammatory than in the hypoinflammatory phenotype (p<0·0001 for all). Classifier models indicated strong concordance between sepsis phenotypes and previously identified ARDS phenotypes (area under the curve 0·87-0·96, depending on the model). Findings were similar excluding participants with both sepsis and ARDS. In PROWESS-SHOCK, 1142 (68·0%) of 1680 patients had the hypoinflammatory phenotype and 538 (32·0%) had the hyperinflammatory phenotype, and response to activated protein C differed by phenotype (p=0·0043). In VASST, phenotype proportions were similar to other cohorts; however, no treatment interaction with the type of vasopressor was observed (p=0·72)., Interpretation: Molecular phenotypes previously identified in ARDS are also identifiable in multiple sepsis cohorts and respond differently to activated protein C. Molecular phenotypes could represent a treatable trait in critical illness beyond the patient's syndromic diagnosis., Funding: US National Institutes of Health., Competing Interests: Declaration of interests PS reports funding from the US National Institutes of Health (NIH) and National Institute of General Medical Sciences; and consulting fees from AstraZeneca. LBW reports funding from NIH, Department of Defense (DoD), Genentech, Boehringer Ingelheim, and CSL Behring; consulting fees from Akebia Therapeutics, Santhera, Global Blood Therapeutics, and Boehringer Ingelheim; and stock options in Virtuoso Surgical. CSC reports funding from NIH; research grants from Roche Genentech and Quantum Leap Healthcare Collaborative; consulting fees from Vasomune Therapeutics, GEn1E Lifesciences, NGM Bio, Cellenkos, and Janssen; and a patent on metagenomic sequencing for sepsis diagnosis (co-recipient). MAM reports funding from Roche Genentech, Quantum Therapeutics, NIH/National Heart, Lung, and Blood Institute/National Institute of Allergy and Infectious Diseases, DoD, and California Institute for Regenerative Medicine; and consulting fees from Johnson & Johnson, Gilead Sciences, and Novartis. MMC reports funding from NIH and DoD; and intellectual property royalties from an issued patent (#11 410 777). JAR reports an investigator-initiated grant from Grifols provided to and administered by the University of British Columbia, Canadian Institutes of Health Research; three grants from the St Paul's Foundation; patents owned by the University of British Columbia related to the use of PCSK9 inhibitor(s) in sepsis and the use of vasopressin in septic shock, and by Ferring Pharmaceuticals for use of selepressin in septic shock; formerly being a founder, Director, and shareholder in Cyon Therapeutics (now closed); being a shareholder in Molecular You; receiving consulting fees in the last 3 years from SIB, Ferring Pharmaceuticals, and Par Pharmaceutical; and having been a funded member of the Data and Safety Monitoring Board of an NIH-sponsored trial of plasma in COVID-19 (PASS-IT-ON). KDL reports grants from NIH: National Institute of Diabetes and Digestive and Kidney Diseases; consulting fees from bioMérieux, UpToDate, SeaStar Medical, AM-Pharma, and Baxter; and stock or stock options in Amgen. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Study Objective: To assess changes in biological measures of acute stress in surgeons during surgery in real-world settings DESIGN: A prospective cohort study., Setting: A tertiary teaching hospital., Patients: 8 consultant and 9 training gynecologists., Intervention: A total of, 161 elective gynecologic surgeries of 3 procedures: laparoscopic hysterectomy, laparoscopic excision of endometriosis, or hysteroscopic myomectomy., Measurements and Main Results: Changes in surgeons' biological measures of acute stress while undertaking elective surgery. Salivary cortisol, mean and maximum heart rate (HR), and indices of the HR variability were recorded before and during surgery. From baseline to during surgery over the cohort, salivary cortisol decreased from 4.1 nmol/L to 3.6 nmol/L (p = .03), maximum HR increased from 101.8 beats per min (bpm) to 106.5 bpm (p <.01), root mean square of standard deviation decreased from 51.1 ms to 39.0 ms (p <.01), and standard deviation of beat-to-beat variability decreased from 73.7 to 59.8 ms (p <.01). Analysis of individual changes in stress by participant-surgery event by paired data graphs reveal inconsistent direction of change in all measures of biological stress despite stratification by surgical experience, role in surgery, level of training, or type of surgery performed., Conclusion: This study measured biometric stress changes at both a group and individual level in real-world, live surgical settings. Individual changes have not previously been reported and the variable direction of stress change by participant-surgery episode identified in this study demonstrates a problematic interpretation of mean cohort findings previously reported. Results from this study suggest that either live surgery with tight environment control or surgical simulation studies may identify what, if any, biological measures of stress can predict acute stress reactions during surgery., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the efficacy and safety of mechanical bowel preparation (MBP) before benign laparoscopic or vaginal gynecologic surgeries., Data Sources: Database searches of MEDLINE (PubMed), Embase (OVID), Cochrane Central Register of Controlled Trials, and Web of Sciences and citations and reference lists published up to December 2021., Methods of Study Selection: Randomized clinical trials in any language comparing MBP with no preparation were included. Two reviewers independently screened 925 records and extracted data from 12 selected articles and assessed the risk of bias with the Cochrane risk-of-bias tool for randomized trials tool. A random-effects model was used for the analysis. Surgeon findings (surgical field view, quality of bowel handling and bowel preparation), operative outcomes (blood loss, operative time, length of stay, surgical site infection), and patient's preoperative symptoms and satisfaction were collected., Tabulation, Integration, and Results: Thirteen studies (1715 patients) assessing oral and rectal preparations before laparoscopic and vaginal gynecologic surgeries were included. No significant differences were observed with or without MBP on surgical field view (primary outcome, risk ratio [RR] 1.01, 95% confidence interval [CI] 0.97-1.05, p = .66, I 2  = 0%), bowel handling (RR 1.01, 95% CI 0.95-1.08, p = .78, I 2  = 67%), or bowel preparation. In addition, there were no statistically significant differences in perioperative findings. MBP was associated with increased pain (mean difference [MD] 11.62[2.80-20.44], I 2  = 76, p = .01), weakness (MD 10.73[0.60-20.87], I 2  = 94, p = .04), hunger (MD 17.52 [8.04-27.00], I 2  = 83, p = .0003), insomnia (MD 10.13[0.57-19.68], I 2  = 82, p = .04), and lower satisfaction (RR 0.68, 95% CI 0.53-0.87, I 2  = 76%, p = .002) compared with controls., Conclusions: MBP has not been associated with improved surgical field view, bowel handling, or operative outcome. However, in view of the adverse effects induced, its routine use before benign gynecologic surgeries should be abandoned., (Copyright © 2023 AAGL. Published by Elsevier Inc. All rights reserved.)

Background: Postmenopausal vaginal symptoms affect over 60% of women and may substantially impact a woman's quality of life. Since 2012, fractional CO 2 laser has been suggested as a treatment for this indication. Structural assessment of vaginal epithelium using microscopic biopsy examination has been used as a primary outcome measure and surrogate determinant of success of vaginal laser in previous clinical studies., Objective: This study aimed to report the effects of laser compared with sham treatment on human vaginal epithelium from postmenopausal women using microscopic examination of tissue biopsies., Study Design: This single-center double-blind, sham-controlled randomized controlled trial was performed in a tertiary hospital in Sydney, Australia. A total of 49 postmenopausal women who were symptomatic of at least 1 vaginal symptom (vaginal dryness, burning, itching; dyspareunia; or dryness) were randomized to either laser or sham treatment. For this nested histologic study, participants had a pre- and post-treatment vaginal wall biopsy collected. Biopsy samples were analyzed by 3 independent specialist gynecologic pathologists and categorized as Type 1 (well-estrogenized), 2 (poorly estrogenized), or 3 (combination) mucosae. Other outcomes assessed included symptom severity (visual analog scale for symptoms including most bothersome symptom, and Vulvovaginal Symptom Questionnaire) and Vaginal Health Index. Prespecified secondary analyses of data were performed. Categorical data were analyzed using the Pearson chi-square test (or Fisher exact test if <5 in any category) or related-samples McNemar test for paired nonparametric data. Nonparametric, continuous variables were assessed using Wilcoxon signed-rank test or Mann-Whitney U test, and parametric variables with t test or 1-way analysis of variance as appropriate. All analyses were performed using SPSS software version 26.0 (IBM Corp, Armonk, NY)., Results: There was no significant difference in microscopic features of vaginal epithelium following laser or sham treatment (P=.20). Further subgroup analyses of age, menopause type, duration of reproductive life, time since menopause and BMI, still demonstrated no significant difference between laser and sham groups in histological category of vaginal epithelium. Microscopic features at pre-treatment vaginal biopsy were Type 1 in 27% (13/49). There was no significant difference in VAS score for overall vaginal symptom between those classified as Type 1 vs. Type 2/3 (VAS score overall: Type 1 vs. Type 2/3, (48.1 [95% CI 27.0, 69.2] vs. 61.5 [95% CI 49.8, 73.3]; P=.166)., Conclusion: Data from this double-blind, sham-controlled randomized controlled trial demonstrate that fractional CO 2 laser and sham treatment have a comparable histologic effect on vaginal tissue that is not significantly different. Fractional CO 2 laser is not significantly different from sham treatment and should not be recommended for clinical use for postmenopausal vaginal symptoms., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Caesarean scar pregnancy (CSP) is an increasingly common clinical conundrum. The non-curettage surgical management of CSP can be categorised into hysteroscopic, vaginal, laparoscopic, and open removal modalities and the choice of treatment is surgeon-dependent. A systematic review of original studies reporting surgical treatment outcomes of CSP until March 2023 was conducted to evaluate the non-curettage surgical management of this highly morbid condition. A total of 60 studies of mostly weak methodological quality were identified involving 6720 CSP cases. Success rates were generally high across all treatment modalities although highest in vaginal and laparoscopic excisional approaches. Morbidity was most associated with haemorrhage although unplanned hysterectomy rates remained low across all treatment groups. Subsequent pregnancies are associated with morbidity despite being underreported and the impact of CSP treatment on future pregnancy is poorly understood. Substantive study heterogeneity precludes meta-analyses of pooled data and treatment superiority has not been demonstrated., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Study Objective: To determine the feasibility of a double-blinded randomized, placebo-controlled study in determining the efficacy of antibiotic prophylaxis in preventing postoperative infections (POIs) in elective nonhysterectomy laparoscopic procedures for benign gynecologic conditions., Design: Double-blinded, randomized, placebo-controlled trial., Setting: University-affiliated tertiary referral hospital in Sydney, Australia., Patients: Women older than 18 years undergoing elective nonhysterectomy laparoscopic procedures for benign gynecologic conditions were eligible for the study and approached., Interventions: Before surgery, participants were randomized to receive either 2-g cephazolin or placebo (10-mL normal saline) administered by the anesthetist. Participants and other research staff were blinded to group allocation., Measurements and Main Results: The primary outcome was study feasibility measured by recruitment rates, compliance rates of drug administration, compliance rates of delivery, maintenance of double blinding, and follow-up rates. Secondary outcomes included rate of POIs, length of hospitalization, readmission to hospital, unscheduled presentations to healthcare facilities, and antibiotic-related reactions. Between February 2019 and March 2021, 170 patients were approached with 117 participants (68.8%) recruited and randomized. The study had a high compliance rate of trial drug delivery (95.7%) and a high follow-up rate (99.1%)., Conclusion: This pilot study has demonstrated feasibility of a large-scale study with a recruitment rate of 68% of patients approached and excellent trial drug delivery and follow-up rates. As anticipated, it is underpowered for identifying clinically significant findings for POI rates. A large-scale study is appropriate and essential to determine the health-related risks of antibiotic prophylaxis with an emphasis on antimicrobial stewardship. The sample size for a large-scale study is 1678 participants based on infection rates in this pilot study., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Purpose: Endometriosis is a chronic inflammatory disease affecting the reproductive, gastrointestinal, and urinary systems. We examined changes in labor force participation amongst women with endometriosis following diagnosis., Methods: We analyzed data from 4494 women born in 1973-78 from the Australian Longitudinal Study on Women's Health. We used multinomial logistic regression models with generalized estimating equations to examine changes in labor force participation amongst 468 women with surgically confirmed endometriosis, and 375 women with clinically suspected endometriosis, relative to a comparison group of 4151 women without endometriosis., Results: At diagnosis, women with surgically confirmed endometriosis were somewhat more likely to be working part-time (OR 1.26, 95% CI 0.94-1.68) or unemployed (OR 1.46, 95% CI 0.96-2.23) than before diagnosis. After diagnosis, women with surgically confirmed endometriosis remained somewhat more likely to be working part-time (OR 1.26, 95% CI 0.88-1.80) but were significantly more likely to be unemployed (OR 1.85, 95% CI 1.16-2.96) than before diagnosis. Labor force participation for women with clinically suspected endometriosis did not differ from women without endometriosis at diagnosis and did not change over time., Conclusions: Women with surgically confirmed endometriosis transitioned out the labor force following diagnosis. Supportive workplace practices may help women remain in the labor force., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Women with lower body mass index (BMI) have a higher risk of surgically confirmed endometriosis but this finding runs counterintuitive to the oestrogen-dependent theory for the disease. Increasingly, endometriosis is diagnosed via non-surgical methods. We examined BMI at age 18-23 years, and changes in BMI, and the risk of endometriosis according to the diagnostic method., Methods: We analysed data from 11 794 young women, born in 1989-95, who completed six surveys as part of an Australian, longitudinal cohort study between 2013 and 2018. Women's survey responses were linked to administrative health records to identify endometriosis. Cox proportional hazards models modelled associations between BMI at age 18-23 years, and changes in BMI, and endometriosis. Analyses were stratified by the diagnostic method of endometriosis: clinically confirmed endometriosis (based on hospital discharge diagnosis) versus clinically suspected endometriosis (women's reports of physician-diagnosed endometriosis)., Results: There were 223 cases of clinically confirmed endometriosis and 396 cases of clinically suspected endometriosis. Women who gained weight after age 18-23 had lower risk of clinically confirmed endometriosis than women without endometriosis whose weight remained stable (HR = 0.64, 95% CI = 0.47-0.88). Women who were overweight (HR = 1.29, 95% CI = 1.01-1.66) at age 18-23 had higher risk of clinically suspected endometriosis than women of normal weight without endometriosis., Conclusions: The risk of clinically confirmed endometriosis was lower among women who gained weight compared to women with stable weight. The risk of clinically suspected endometriosis was higher among women who were overweight compared to normal weight., (Copyright © 2022 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Research Question: Do women with laparoscopically confirmed endometriosis have higher plasma concentrations of circulating cell-free DNA (cirDNA) than those without endometriosis?, Design: Prospective study of women aged 18-45 years undergoing benign gynaecological laparoscopy at two tertiary hospitals. Venous blood was collected immediately before surgery, and women were allocated to the endometriosis or control groups based on surgical findings. Total plasma cirDNA and cirDNA integrity were measured by quantitative polymerase chain reaction (qPCR) targeting short (115 bases) and long (247 bases) ALU segments. Endometrial-derived cirDNA was measured by qPCR of bisulfite-treated cirDNA using primers selective for a FAM101A sequence uniquely unmethylated in endometrial tissue. Five cirDNA parameters were compared between the control and endometriosis cohorts: total cirDNA concentration, long-stranded cirDNA concentration, integrity ratio, endometrial cirDNA concentration and endometrial cirDNA proportion., Results: Twenty-eight endometriosis and 15 control samples were included. Women with and without endometriosis had cirDNA concentrations of 2.24 ± 0.89 ng/ml and 2.56 ± 0.92 ng/ml, respectively. Analysis by phenotype of endometriosis revealed a significantly higher endometrial cirDNA concentration in women with superficial disease (n = 10) compared with deep endometriosis (n = 18) (mean difference 0.14 ng/ml; 95% CI 0.15 to 0.26; P = 0.025), but not with controls., Conclusions: No significant differences were found in any of the cirDNA parameters between women with and without endometriosis. The low statistical power and heterogenous pelvic pathology in the control group render it difficult to determine whether the negative results reflect a true lack of increase in cirDNA in endometriosis., (Copyright © 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Study Objective: To demonstratefull-thickness excision of the affected muscularis along the submucosal plane., Design: Stepwise demonstration of LRSD technique with narrated video footage., Setting: LRSD takes advantage of the submucosal layer of the bowel wall and uses it as an easier line of excision for rectal endometriosis compared with the very difficult traditional line of excision of irregular disease-muscularis interface. The expansion of the submucosal layer by the injection separates the affected muscularis away from the mucosa, making it safer to excise the lesion with less chance of entering the bowel lumen. Excision of disease is more complete with LRSD because the full-thickness excision of the muscularis layer includes the healthy deep muscularis, which will form the disease-free deep excision margin., Intervention: This video will highlight anatomic and technical aspects of LRSD including the following key steps: 1. Mobilization of diseased bowel segment 2. Submucosal injection 3. Circumferential incision of the muscularis 4. Submucosal dissection along the submucosal plane 5. Bowel wall integrity test 6. Muscularis defect repair CONCLUSION: Rectal shaving by LRSD appears to be easier, safer, and more complete in excision of bowel endometriosis than the classical rectal shaving technique. This modification requires further evaluation to confirm its potential in the surgical management of rectosigmoid deep infiltrative endometriosis., (Copyright © 2021 AAGL. All rights reserved.)

Objective: This systematic review examined energy-based treatments of the vagina for postmenopausal vaginal symptoms., Data Sources: We performed a systematic review from April 2017 (the end date of our previous review) to April 2020, searching Medline, Embase, and Scopus., Methods of Study Selection: The inclusion criteria were all randomized studies, prospective studies with >10 cases, and retrospective studies with >20 cases published in English or French that assessed change in postmenopausal vaginal symptoms and/or sexual function in women after energy-based vaginal treatments. Meta-analyses were performed on randomized data., Tabulation, Integration, and Results: Of the 989 results retrieved, 3 randomized studies, 16 prospective studies, and 7 retrospective studies were included in the review, representing data from 2678 participants. Pooled data from 3 randomized controlled trials show no difference between vaginal laser and topical hormonal treatments for change in vaginal symptoms (-0.14, 95% confidence interval -1.07 to 0.80) or sexual function scores (2.22, 95% confidence interval -0.56 to 5.00). Furthermore, no difference among vaginal laser, topical hormone, and lubricant was demonstrated in sexual function (p = .577). As in our previous review, non-randomized data support energy-based treatments in improving vaginal symptoms, sexual function, and clinician-reported outcomes. No severe adverse events were reported in the included studies. Significant heterogeneity of data arising from differing measures and reported outcomes continues to be an issue, with data remaining low quality, with high risk of bias, and no double-blind or placebo-controlled randomized trials yet reported, although 1 has now completed recruitment., Conclusion: There are 3 randomized trials comparing energy-based systems with hormonal treatment, with no clinical difference in these 2 approaches. Although prospective data continue to show promising outcomes, without strong evidence from well-powered, double-blind placebo-controlled trials to determine the efficacy of treatment compared with placebo, the use of energy-based treatments should continue to be undertaken in research studies only, with high-quality studies essentially free from bias (International Prospective Register of Systematic Review registration number: 178346)., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Objective: This study sought to determine the prevalence, tolerability, and self-reported effectiveness of cannabis in women with endometriosis., Methods: A cross-sectional online survey was conducted between October and December 2017. Recruitment targeted women with endometriosis through social media postings from endometriosis advocacy groups. Women aged 18 to 45, living in Australia, and with surgically confirmed endometriosis were eligible to participate. Survey questions investigated the types of self-management used, change in symptoms or medication use, costs, and adverse events., Results: A total of 484 responses were included for analysis, with 76% of the women reporting the use of general self-management strategies within the last 6 months. Of those using self-management, 13% reported using cannabis for symptom management. Self-reported effectiveness in pain reduction was high (7.6 of 10), with 56% also able to reduce pharmaceutical medications by at least half. Women reported the greatest improvements in sleep and in nausea and vomiting. Adverse effects were infrequent (10%) and minor., Conclusion: Australian law currently requires legal medicinal cannabis use to follow specific, regulated pathways that limit prescription by this method; however, self-reported illicit use of cannabis remains relatively common in Australian women with endometriosis. Women report good efficacy of cannabis in reducing pain and other symptoms, with few adverse effects reported. Further clinical research is warranted to determine the effectiveness of cannabis in managing endometriosis symptoms. In locations where medicinal cannabis is more accessible, there remains a paucity of evidence for its clinical efficacy with endometriosis-associated symptoms., (Copyright © 2019 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Objective: To report on randomized controlled trials (RCTs) that examine the surgical treatment of endometriosis-associated pelvic pain and to highlight their strengths and weaknesses., Data Sources: We performed a systematic review of English-language, full-text articles addressing the surgical management of pain symptoms associated with endometriosis. The terms endometriosis, pain, surgery, laparoscopy, plasma, and laser were used for searches in Cochrane, MEDLINE, EMBASE, and clinical trial databases. Additional studies were identified from references in electronically located articles., Methods of Study Selection: A literature search was conducted by 2 authors, and abstracts were independently screened for inclusion, with the resolution of any discrepancy by a third author. Randomized studies that reported pain before and after surgery were eligible for inclusion. Supporting data from nonrandomized trials were used for discussion. The Cochrane risk-of-bias assessment was performed on included studies., Tabulation, Integration, and Results: Search results for available articles from 1996 to October 2019 revealed 594 potential studies, with 20 studies meeting the final inclusion criteria. Comparative studies of surgery vs no surgery for an effect on pain, surgical approach, the effect of different locations of disease on pain, nerve-dividing techniques for pain, and nerve-sparing effects for pain were studied. RCTs reported a substantial reduction in pain compared with no surgery in up to 80% of women; however, up to a third of women in these studies reported a placebo response. There was no evidence of a difference in pain reduction with the mode of surgery (laparoscopy, laparotomy, or robot-assisted laparoscopy). There is limited evidence stating that excision is superior to ablative surgery; however, there are confounders in the reporting of disease location and depth and the pain symptoms most affected. We need to reconsider the hypothesis that disc excision results in fewer complications and has superior outcomes to those of segmental resection in light of the first RCT on this subject. Nerve-dividing surgery for pain has been demonstrated to be of no value for uterosacral nerve ablation and/or division and of limited (if any) value for presacral neurectomy., Conclusion: Although surgical RCTs have always been difficult to undertake, there are 16 RCTs on endometriosis-associated pain. Ethical considerations, the equipoise of surgeons and participants, and follow-up duration are important parameters in establishing RCTs. In addition, we must be willing to accept and adopt the evidence when it does demonstrate a particular outcome, such as the fact that surgical uterosacral nerve disruption does not improve pain or that disc excision does not substantially reduce complications compared with segmental resection for bowel disease, as suggested by previous nonrandomized studies. If we accept that a well-conducted RCT provides best-quality evidence, then we should at least be open to the possibility that our long-held views may be challenged and changed with new science in our practice., (Copyright © 2019 AAGL. All rights reserved.)

Background: Treatment with bone-marrow-derived mesenchymal stromal cells (MSCs) has shown benefits in preclinical models of acute respiratory distress syndrome (ARDS). Safety has not been established for administration of MSCs in critically ill patients with ARDS. We did a phase 2a trial to assess safety after administration of MSCs to patients with moderate to severe ARDS., Methods: We did a prospective, double-blind, multicentre, randomised trial to assess treatment with one intravenous dose of MSCs compared with placebo. We recruited ventilated patients with moderate to severe ARDS (ratio of partial pressure of oxygen to fractional inspired oxygen <27 kPa and positive end-expiratory pressure [PEEP] ≥8 cm H 2 O) in five university medical centres in the USA. Patients were randomly assigned 2:1 to receive either 10 × 10 6 /kg predicted bodyweight MSCs or placebo, according to a computer-generated schedule with a variable block design and stratified by site. We excluded patients younger than 18 years, those with trauma or moderate to severe liver disease, and those who had received cancer treatment in the previous 2 years. The primary endpoint was safety and all analyses were done by intention to treat. We also measured biomarkers in plasma. MSC viability was tested in a post-hoc analysis. This trial is registered with ClinicalTrials.gov, number NCT02097641., Findings: From March 24, 2014, to Feb 9, 2017 we screened 1038 patients, of whom 60 were eligible for and received treatment. No patient experienced any of the predefined MSC-related haemodynamic or respiratory adverse events. One patient in the MSC group died within 24 h of MSC infusion, but death was judged to be probably unrelated. 28-day mortality did not differ between the groups (30% in the MSC group vs 15% in the placebo group, odds ratio 2·4, 95% CI 0·5-15·1). At baseline, the MSC group had numerically higher mean scores than the placebo group for Acute Physiology and Chronic Health Evaluation III (APACHE III; 104 [SD 31] vs 89 [33]), minute ventilation (11·1 [3·2] vs 9·6 [2·4] L/min), and PEEP (12·4 [3·7] vs 10·8 [2·6] cm H 2 O). After adjustment for APACHE III score, the hazard ratio for mortality at 28 days was 1·43 (95% CI 0·40-5·12, p=0·58). Viability of MSCs ranged from 36% to 85%., Interpretation: One dose of intravenous MSCs was safe in patients with moderate to severe ARDS. Larger trials are needed to assess efficacy, and the viability of MSCs must be improved., Funding: National Heart, Lung, and Blood Institute., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

K-RAS is mutated in approximately 30% of human cancers, resulting in increased RAS signaling and tumor growth. Thus, RAS is a highly validated therapeutic target, especially in tumors of the pancreas, lung and colon. Although directly targeting RAS has proven to be challenging, it may be possible to target other proteins involved in RAS signaling, such as the guanine nucleotide exchange factor Son of Sevenless (SOS). We have previously reported on the discovery of small molecules that bind to SOS1, activate SOS-mediated nucleotide exchange on RAS, and paradoxically inhibit ERK phosphorylation (Burns et al., PNAS, 2014). Here, we describe the discovery of additional, structurally diverse small molecules that also bind to SOS1 in the same pocket and elicit similar biological effects. We tested >160,000 compounds in a fluorescence-based assay to assess their effects on SOS-mediated nucleotide exchange. X-Ray structures revealed that these small molecules bind to the CDC25 domain of SOS1. Compounds that elicited high levels of nucleotide exchange activity in vitro increased RAS-GTP levels in cells, and inhibited phospho ERK levels at higher treatment concentrations. The identification of structurally diverse SOS1 binding ligands may assist in the discovery of new molecules designed to target RAS-driven tumors., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Uterine septa are a class of müllerian duct anomaly that, similar to other classes, are associated with poor reproductive outcomes; however, they are unique because these poor outcomes, particularly recurrent pregnancy loss, may be responsive to surgical correction. The current evidence regarding septoplasty is difficult to interpret because the definitions of a uterine septum, methods to diagnose it, and hysteroscopic techniques used for treatment are variable and generally of poor to moderate quality. Robust data on outcomes, particularly live births, after septoplasty are not available at this time. This review aims to examine the evidence on this contentious issue. A search of the literature was conducted using the MEDLINE, Embase, and Cochrane databases from 2002 to present with included articles reporting on clinical and/or imaging diagnosis of a uterine septum, operative techniques for uterine septoplasty, or clinical outcomes for women with uterine septa. The initial search revealed 4997 potentially relevant articles with 36 full-text articles included after the removal of nonrelevant titles, including 16 diagnostic studies, 17 surgical studies, and 3 studies on clinical outcomes. Where access to 3-dimensional transvaginal ultrasound or magnetic resonance imaging exists, these imaging modalities offer a highly sensitive and specific method of diagnosing a uterine septum without invasive diagnosis although this is operator dependent. Despite hysteroscopic septoplasty being described for over 40 years, there remains a lack of high-quality data to support hysteroscopic septoplasty and which women would most benefit from the procedure. There is no evidence for pre- or postoperative treatments nor has a single surgical approach been identified as superior than another although an important end point of live birth rates is largely unreported in these trials. Although several classification systems have been described, the diagnostic categorization of septal variants has limited a meaningful approach to this issue in both the clinical and research setting., (Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)

The objective of this systematic review was to assess the efficacy and safety of treatment options of cesarean scar pregnancies (CSPs). We searched MEDLINE, Embase, and the Cochrane Library from inception to June 2016 as well as reference lists. We included English publications reporting treatment outcomes of at least 10 cases of CSPs. Two authors screened for eligibility, extracted data, and assessed the quality of the included studies. Treatment was considered successful if no subsequent intervention was required after the index treatment. Of the 1257 citations identified, 63 studies were eligible. The overall success rate of systemic methotrexate (MTX) and/or local injection of MTX or potassium chloride was 62%. Dilation and curettage (D&C) was associated with a 28% risk of hemorrhage that dropped to 4% when combined with uterine artery embolization (UAE). Hysteroscopic resection of CSP was unsuccessful in 12% of cases, and inadequate human chorionic gonadotropin decay was the primary indication for additional intervention. Laparoscopic, vaginal, and open excision and repair of the defect were associated with a high success rate (≥96%) and a low risk of hemorrhage (≤4%). Expectant management resulted in a 57% live birth rate, but 63% of women required hysterectomy because of placental implantation abnormalities or second trimester uterine rupture. Most studies were of low methodologic quality, and given the heterogeneity between the studies and groups, statistical comparison of treatment options was deemed inappropriate. In conclusion, the decision to allow the progression of CSPs exposes women to a high risk of life-threatening hemorrhage and hysterectomy. Medical treatment options alone are often insufficient. D&C is a reasonable option in well-selected women or when combined with UAE. The potential benefits of excision and repair of scar defect on further pregnancy outcomes need to be further assessed., (Copyright © 2017 AAGL. Published by Elsevier Inc. All rights reserved.)

The complex pathogenesis and variable presentation of adenomyosis make it one of the most difficult of the FIGO PALM-COIEN abnormal uterine bleeding group to diagnose and treat. Basic clinical parameters such as prevalence are difficult to accurately assess because histological confirmation is usually employed; however, because of the access to and accuracy and utilization of transvaginal ultrasound and other advanced imaging techniques such as MRI, noninvasive diagnosis is recognized to be highly accurate. The clinical symptoms of pain, abnormal uterine bleeding, and subfertility are the primary presentations of adenomyosis with increasing data supporting a substantial role of this disease in reducing fecundity and interfering with assisted reproductive interventions. Treatments have been aimed at managing symptoms and improving fertility options. Management by hysterectomy is not always desired by women, and with many women having children in their fourth and even fifth decades, it is often not reasonable to consider this radical option., (Copyright © 2016. Published by Elsevier Ltd.)

Methicillin-resistant Staphylococcus aureus (MRSA) has been detected in retail meats, although large-scale studies are scarce. We conducted a one-year survey in 2010-2011 within the framework of the National Antimicrobial Resistance Monitoring System. Among 3520 retail meats collected from eight U.S. states, 982 (27.9%) contained S. aureus and 66 (1.9%) were positive for MRSA. Approximately 10.4% (107/1032) of S. aureus isolates, including 37.2% (29/78) of MRSA, were multidrug-resistant (MDRSA). Turkey had the highest MRSA prevalence (3.5%), followed by pork (1.9%), beef (1.7%), and chicken (0.3%). Whole-genome sequencing was performed for all 66 non-redundant MRSA. Among five multilocus sequence types identified, ST8 (72.7%) and ST5 (22.7%) were most common and livestock-associated MRSA ST398 was assigned to one pork isolate. Eleven spa types were represented, predominately t008 (43.9%) and t2031 (22.7%). All four types of meats harbored t008, whereas t2031 was recovered from turkey only. The majority of MRSA (84.8%) possessed SCCmec IV and 62.1% harbored Panton-Valentine leukocidin. Pulsed-field gel electrophoresis showed that all ST8 MRSA belonged to the predominant human epidemic clone USA300, and others included USA100 and USA200. We conclude that a diverse MRSA population was present in U.S. retail meats, albeit at low prevalence., (Published by Elsevier Ltd.)

Campylobacter spp. commonly cause gastrointestinal illness in humans. Poultry meats have long been considered the predominant source of these infections, but few in-depth Campylobacter source attribution studies have been completed. We analyzed more than 1,300 Campylobacter isolates recovered from a number of animal and food sources, including dairy and beef cattle, pigs, poultry, and retail poultry meat, and compared them with Campylobacter isolates recovered from human clinical samples. Each isolate was subtyped using pulsed-field gel electrophoresis (PFGE) with SmaI and queried against the Centers for Disease Control and Prevention PulseNet database to identify human isolates with indistinguishable patterns. Half (49.5%) of the PFGE patterns from poultry animal and retail meat isolates were indistinguishable from patterns of at least one human isolate. Among the isolates from beef and dairy cows, 56.6 and 65.0%, respectively, of their PFGE patterns were indistinguishable from those of human isolates. Only a small portion of the PFGE patterns of Campylobacter isolated from pigs (9.5%) were found to have PFGE patterns in common with human isolates. These data imply that cattle may be larger contributors to Campylobacter infections than previously recognized and help further our understanding of potential sources of human campylobacteriosis.

Objective: To determine the effectiveness of the MyoSure intrauterine mechanical morcellator device for removal of intrauterine pathology., Design: Prospective cohort study (Canadian Task Force classification II-2)., Intervention: This study was performed at the Royal Hospital for Women and Prince of Wales Private Hospital, Sydney, Australia. All women undergoing hysteroscopic removal of intrauterine pathology using the MyoSure device between January 2013 and June 2015 were included., Results: A total of 255 MyoSure procedures were performed, with 61% performed by trainees. Resection of leiomyomas occurred in 40% or cases, polyps in 39%, combination pathology in 9%, pregnancy products in 6%, and preinvasive or invasive disease in 5% of cases. Complete resection of pathology was achieved in 92% of polyps, 66% of leiomyomas, and 87% of pregnancy tissue. Leiomyomas were more likely to be completely resected when surgery was performed by an attending physician or senior resident, however there was no statistically significant difference in clinical outcomes. When leiomyomas were stratified according to size, 87% of leiomyomas ≤40 mm were completely resected with only 48% of leiomyomas >40 mm completely resected with the index surgery. No intraoperative complications occurred. Postoperative outcomes included symptom resolution in 76%, further surgery (repeat hysteroscopy or hysterectomy) in 10%, pregnancy in 2%, and medical/conservative management in 12% of patients., Conclusion: The MyoSure device is very effective when used to resect endometrial polyps. Leiomyomas >40 mm are unlikely to be completely resected at a single operation when using the MyoSure device. Similar clinical outcomes were obtained when procedures were performed by trainees compared to senior clinicians., (Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.)

Study Objective: Mechanical bowel preparation (MBP) continues to be widely used in gynecologic surgery, with the aim of reducing postoperative complications and improving the viewing and handling conditions in the surgical field. It is reported that MBP is an unpleasant patient experience and may be associated with adverse effects such as dehydration and electrolyte imbalance. This review evaluates the use of preoperative MBP compared with no MBP in adult patients undergoing open abdominal, laparoscopic, or vaginal surgery. Although the focus is on the use of MBP for gynecologic procedures, data from other surgical areas are covered when relevant., Design: A comprehensive search of the databases Medline (from 1946), EMBASE (from 1947), PubMed, Cochrane Library Central (Register of Controlled Trials), and Google Scholar was performed to identify any randomized controlled trials (RCTs) and prospective or retrospective cohort studies comparing preoperative MBP to no MBP., Results: Forty-three studies were identified in various surgical specialties, of which there were 5 RCTs in gynecology. The gynecologic studies reported no benefit for MBP in operative time or improved surgical field of view but did report a more unpleasant patient experience when MBP is used. RCTs from colorectal and urologic surgery were powered for infectious morbidity and anastomotic leak and did not demonstrate improved patient outcomes when MBP was used., Conclusion: Evidence from high-quality trials reports no or few benefits from MBP or rectal enema across surgical specialties. In the field of gynecologic surgery, high-quality evidence supports the view that MBP may be safely abandoned., (Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.)

PCR-based typing methods, such as repetitive sequence-based PCR (rep-PCR), may facilitate the identification of Shiga toxin-producing Escherichia coli (STEC) by serving as screening methods to reduce the number of isolates to be processed for further confirmation. In this study, we used a commercial rep-PCR typing system to generate DNA fingerprint profiles for STEC O157 (n = 60) and non-O157 (n = 91) isolates from human, food, and animal samples and then compared the results with those obtained from pulsed-field gel electrophoresis (PFGE). Fifteen serogroups were analyzed using the Kullback Leibler or extended Jaccard statistical method, and the unweighted pair group method of averages algorithm was used to create dendrograms. Among the 151 STEC isolates tested, all were typeable by rep-PCR. Among the non-O157 isolates, rep-PCR clustered 79 (88.8%) of 89 isolates according to serogroup status, with peak differences ranging from 1 (96.4% similarity) to 12 (58.7% similarity). The genetic relatedness of the non-O157 serogroups mirrored the branching of distinct clonal groups elucidated by other investigators. Although the discriminatory power of rep-PCR (Simpson's index of diversity [SID] = 0.954) for the O157 isolates was less than that of PFGE (SID = 0.993), rep-PCR was able to identify 29 pattern types, suggesting that this method can be used for strain typing, although not to the same level as PFGE. Similar results were obtained from analysis of the non-O157 isolates. With rep-PCR, we assigned non-O157 isolates to 46 pattern types with a SID of 0.977. By PFGE, non-O157 STEC strains were divided into 77 pattern types with a SID of 0.996. Together, these results indicate the ability of the rep-PCR typing system to distinguish between and within O157 and non-O157 STEC groups. Rapid PCR-based typing methods could be invaluable tools for use in outbreak investigations by excluding unrelated STEC isolates within 24 h.

Study Objective: To identify the biomechanical movements of laparoscopic surgeons during laparoscopic gynecologic procedures, and to determine whether such movements can be assessed and measured both temporally and biomechanically., Design: Prospective descriptive kinematic study (Canadian Task Force classification II-3)., Setting: A tertiary referral hospital in Sydney, Australia., Study Subjects: Five gynecologic laparoscopic surgeons., Interventions: Video recording from a variety of fixed positions to assess surgeon stance, time spent in specific postures, and relative change of limb angles during laparoscopic surgical procedures., Measurements and Main Results: Postoperative review of surgical movements during laparoscopic surgery was able to provide quantitative data. Motion and timing could be classified by angle banding ranges among surgeons. The most extreme shoulder abduction angles occurred during trocar insertion (61°) and insertion or removal of laparoscopic instruments (63.5°), with procedures involving morcellation requiring the greatest number of instrument insertions or removals (n = 57). The elbow is most frequently in a neutral position in TLH, and the shoulder spends the most time in abduction during myomectomy., Conclusion: This proof-of-concept study confirms that detailed ergonomic assessment is possible within live surgical settings, with identified limitations. This study may allow for a larger-scale study to determine at-risk movements during the various phases of a laparoscopic surgery and possibly control for some of these hazardous behaviors., (Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.)

Eleven Salmonella enterica serovar Bovismorbificans isolates obtained from the U.S. District of Columbia during a 2011 hummus-associated foodborne outbreak were compared to 12 non-outbreak isolates. All isolates from the outbreak demonstrated a single PFGE pattern that was distinctly different from other isolates of S. Bovismorbificans as recorded in the PulseNet Database. Results from molecular analyses of the hummus-associated S. Bovismorbificans isolates indicate that the isolates from the outbreak were unique and have acquired an 80-90 kb plasmid. The impact of this study is that the information gained will add and expand our knowledge of diversity of the S. Bovismorbificans serovar., (Published by Elsevier Ltd.)

Entry to the peritoneal cavity for laparoscopic surgery is associated with defined morbidity, with all entry techniques associated with substantial complications. Debate over the safest entry technique has raged over the last 2 decades, and yet, we are no closer to arriving at a scientifically valid conclusion regarding technique superiority. With hundreds of thousands of patients required to perform adequately powered studies, it is unlikely that appropriately powered comparative studies could be undertaken. This review examines the risk of complications related to laparoscopic entry, current statements from examining bodies around the world, and the medicolegal ramifications of laparoscopic entry complications. Because of the numbers required for any complications study, with regard to arriving at an evidence-based decision for laparoscopic entry, we ask: is the current literature perhaps as good as it gets?, (Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.)

Laparoscopic myomectomy is a common surgical treatment for symptomatic uterine leiomyomas. Proponents of the laparoscopic approach to myomectomy propose that the advantages include shorter length of hospital stay and recovery time. Others suggest longer operative time, greater blood loss, increased risk of recurrence, risk of uterine rupture in future pregnancies, and potential dissemination of cells with use of morcellation. This review outlines techniques for performance of laparoscopic myomectomy and critically appraises the available evidence for operative data, short-term and long-term complications, and reproductive outcomes., (Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.)