Positron emission tomography in the evaluation of endometriosis: A systematic review.

Despite the profound impact of endometriosis worldwide, delays in diagnosis and suboptimal surveillance techniques are well-recognised issues. Case studies have reported incidental uptake of 18F-FDG PET tracer in endometriotic lesions. However, the utility of PET imaging as a non-invasive diagnostic tool for endometriosis is currently unclear. The purpose of this systematic review was to summarise the existing evidence and determine the value of available PET scanning techniques in the detection and monitoring of endometriosis. MEDLINE, EMBASE, CENTRAL, SCOPUS and Web of Science were searched from conception to 05/03/23. Eligible studies included participants with a history of known or suspected endometriosis who underwent a PET scan for any indication. All PET tracers and protocols were eligible. Outcomes included correlation of PET tracer uptake with the presence of endometriosis seen at laparoscopy or confirmed on histology, sensitivity of tracer uptake, specificity of tracer uptake, site of lesions with tracer uptake, stage of lesions with tracer uptake, SUVmax of endometriosis lesions and adverse reactions to PET imaging. The protocol for this review was registered with PROSPERO (ID: CRD42023405260). Eight studies describing 110 participants were eligible for inclusion. Six studies assessed 18F-FDG with combined PET-CT, one study assessed 18F-FDG PET alone, and the remaining study assessed PET-CT with an alternative tracer, 68Ga-DOTATATE. For 18F-FDG imaging, the correlation of PET avidity with lesions or sites of endometriosis ranged from 0-55 %. Pre-operative 68Ga-DOTATATE PET-CT detected endometriosis in 33 % of cases. All included studies were cohort studies, six were assessed to have low risk of bias, one with moderate risk and one with high risk of bias. Overall, 18F-FDG PET scanning does not appear to consistently identify endometriotic lesions, and therefore its reliability and usefulness in endometriosis diagnosis is limited. The utility of 68Ga-DOTATATE PET-CT remains uncertain. Findings are constrained by limited available evidence reporting outcomes of PET imaging for endometriosis. Other existing PET tracers with biological plausibility in the detection or monitoring of endometriosis warrant further investigation.

Longitudinal Changes of Depressive Symptoms in Sedentary Women Who Exercised During Pregnancy.

Introduction: Prenatal depression is a common disorder; however, little is known about how depressive symptoms manifest during pregnancy, including when symptoms present and what symptoms are common. This study aimed to better understand prenatal depressive symptoms during pregnancy in the postpartum period, as well as how exercise, such as walking and stretching, can improve depressive symptoms during pregnancy and the postpartum period. Methods: A total of 55 women were assessed using the Beck Depression Inventory-II for depressive symptoms at 16 weeks, 28 weeks, and 2 months postpartum. Sedentary pregnant women at-risk for preeclampsia were randomly assigned to either a stretching or walking group for 40 minutes five times a week from 18 weeks of gestation until birth. The primary analyses were analysis of variance and mixed-effects models. Results: All depressive symptoms decreased throughout pregnancy during the postpartum period, although this trend was not statistically significant. Cognitive-affective and somatic depressive symptoms had different trajectories during pregnancy into the postpartum period, but no significant difference was found. Statistically significant improvements were observed in loss of energy and change in sleeping pattern for the walking and stretching groups. Conclusion: The finding that physical activity improves the depressive symptoms' loss of energy and changes in sleeping patterns during pregnancy aligns with the existing literature, but little research has examined how individual depressive symptoms change throughout pregnancy into the postpartum period. Gaining a better understanding of the trajectories and manifestations of depressive symptoms during pregnancy and the postpartum period is essential for improving detection and treatment practices. Understanding when and how depressive symptoms are present is critical for the clinical diagnosis of this disorder.

In-vitro modeling of intravenous drug precipitation by the optical spatial precipitation analyzer (OSPREY).

Intravenous (IV) administration of poorly water-soluble small molecule therapeutics can lead to precipitation during mixing with blood. This can limit characterization of pharmacological and safety endpoints in preclinical models. Most often, tests of kinetic and thermodynamic solubility are used to optimize the formulation for solubility prior to infusion in animals, but these do not capture the dynamic precipitation processes that take place during in-vivo administration. To better capture the fluid dynamic processes that occur during IV administration, we developed the Optical Spatial PREcipitation analYzer (OSPREY) as a method to quantify the amount and size of compound precipitates in whole blood using a flow-through system that mimics IV administration. Here, we describe the OSPREY device and its underlying imaging processing methods. We then validate the ability to accurately segment particles according to their size using monodisperse suspensions of microspheres (diameter 50 to 425 µm). Next, we use a tool compound, ABT-737, to study the effects of compound concentration, vessel flow rate, compound infusion rate and vessel diameter on precipitation. Finally, we use the physiological diameter and flow rate of rat femoral vein and dog saphenous vein to demonstrate the potential of OSPREY to model in-vivo precipitation in a controlled, dynamic in-vitro assay.

Multiple Case Study Exploring the Impact of Visitor Restrictions in Hospitals on Childbirth Support during the COVID-19 Pandemic.

Objective: Childbirth is a life-changing experience for new mothers, birth partners, and families. The COVID-19 pandemic restricted laboring mothers' access to support in hospitals through visitor restrictions. The goal of this research was to describe childbirth support in hospitals during the COVID-19 pandemic. Methods: A qualitative study using a multiple case study design describes childbirth support in hospitals during the COVID-19 pandemic from the perspectives of the new mother, birth partner, and obstetric hospital staff, including doulas, nurses, and obstetric providers. The setting was a large metropolitan area in South Texas. Sixteen participants were interviewed including four new mothers, three birth partners, three doulas, three obstetric nurses, and three obstetric providers. Results: Themes that emerged from the data include: under a spotlight, unmet expectations, discovering serenity, and quality childbirth support. Conclusion: During the pandemic, new mothers and birth partners experienced fewer distractions, better communication with the hospital staff, and had better opportunities to bond with the newborn during labor and after birth, but did report missing the presence of their family and friends. Doulas, obstetric nurses, and obstetric providers found they were able to provide better quality and safer care to laboring mothers and birth partners.

We live in a virtual world: Training the trainee using an integrated visual reality simulator curriculum.

BACKGROUND: Gynaecology trainees struggle to obtain adequate procedural experience. Training programs integrating virtual reality simulators (VRS) have been suggested as a solution. AIMS: The study aimed to assess if a VRS training program (LapSim® , Surgical Sciences, Göteborg, 2017) improved live operating performance at six months for novice and experienced trainees. Additional outcomes included the association between LapSim® logged time and live operating performance at six months, LapSim® scores and live operating performance at zero and sixmonths and the difference in benefit for novice and experienced gynaecology trainees. METHODS: A prospective intervention study was conducted. Novice and experienced trainees were enrolled, and comparisons made at zero- and six-month time points. The intervention groups were provided with a laparoscopic gynaecology curriculum incorporating VRS. Controls underwent routine training only. Assessment of live operating performance was conducted after six months training. RESULTS: Thirty-five trainees participated, and 25 had access to the VRS curriculum (17 novice and eight experienced trainees). Access to the VRS curriculum and time spent training on the LapSim® made no difference to live operating ability for either intervention group (P > 0.05). The median (interquartile range) hours of VRS usage were 7.9 (4.5-10.8) and 6.0 (4.0-6.8) for novice and experienced trainees respectively. The intervention group provided positive feedback on the utility of VRS in their laparoscopic skill development. CONCLUSION: Optimal utilisation of VRS in Australian training paradigms remains incompletely understood. Further research is required to establish the most effective integration of VRS into training models to ensure uptake and transferability to the operating theatre.

Peripheral, Central, and Cross Sensitization in Endometriosis-Associated Pain and Comorbid Pain Syndromes.

Endometriosis-associated pain and the mechanisms responsible for its initiation and persistence are complex and difficult to treat. Endometriosis-associated pain is experienced as dysmenorrhea, cyclical pain related to organ function including dysuria, dyschezia and dyspareunia, and persistent pelvic pain. Pain symptomatology correlates poorly with the extent of macroscopic disease. In addition to the local effects of disease, endometriosis-associated pain develops as a product of peripheral sensitization, central sensitization and cross sensitization. Endometriosis-associated pain is further contributed to by comorbid pain conditions, such as bladder pain syndrome, irritable bowel syndrome, abdomino-pelvic myalgia and vulvodynia. This article will review endometriosis-associated pain, its mechanisms, and its comorbid pain syndromes with a view to aiding the clinician in navigating the literature and terminology of pain and pain syndromes. Limitations of our current understanding of endometriosis-associated pain will be acknowledged. Where possible, commonalities in pain mechanisms between endometriosis-associated pain and comorbid pain syndromes will be highlighted.

Multimedia in improving informed consent for caesarean section: A randomised controlled trial.

BACKGROUND: Multimedia modules have been used as an adjunct to improve patient knowledge and recall for various elective surgical procedures, but have been incompletely evaluated in patients undergoing caesarean section. AIMS: To compare the use of a supplementary multimedia module with written information in improving the informed consent process prior to elective caesarean section. MATERIALS AND METHODS: This was a prospective randomised controlled trial (ACTRN12616000430437). Primary outcomes were knowledge and anxiety scores immediately following the intervention and on the day of surgery. Secondary outcomes were patient satisfaction, length of stay, time to cessation of analgesia, and patient assessment of the consent types. RESULTS: Seventy-five patients completed the study. Both multimedia module and written information groups demonstrated a significant increase in knowledge scores with no difference between the groups. In the multimedia-assisted consent group, scores improved from baseline by +2.31 (P < 0.001) immediately after watching the multimedia module and by +2.41 (P < 0.001) on the day of surgery. In the written information group, scores improved by +1.76 (P < <0.001), and +2.31 (P < 0.001) respectively. There was no adverse impact on anxiety in either group. Patient-reported understanding (92.4% vs 78.5%, P = 0.001), and helpfulness (90.1% vs 73.3%, P = 0.001) was significantly higher in the multimedia module group than in the written information group. The multimedia module was assessed as 'slightly too long' and provided 'slightly too much information'. CONCLUSIONS: Multimedia modules are a valuable adjunct to traditional processes of obtaining informed consent for elective caesarean section and should be offered and made available to patients prior to surgery.

64Cu-SARTATE PET Imaging of Patients with Neuroendocrine Tumors Demonstrates High Tumor Uptake and Retention, Potentially Allowing Prospective Dosimetry for Peptide Receptor Radionuclide Therapy.

Imaging of somatostatin receptor expression is an established technique for staging of neuroendocrine neoplasia and determining the suitability of patients for peptide receptor radionuclide therapy. PET/CT using 68Ga-labeled somatostatin analogs is superior to earlier agents, but the rapid physical decay of the radionuclide poses logistic and regulatory challenges. 64Cu has attractive physical characteristics for imaging and provides a diagnostic partner for the therapeutic radionuclide 67Cu. Based on promising preclinical studies, we have performed a first-time-in-humans trial of 64Cu-MeCOSar-Tyr3-octreotate (64Cu-SARTATE) to assess its safety and ability to localize disease at early and late imaging time-points. Methods: In a prospective trial, 10 patients with known neuroendocrine neoplasia and positive for uptake on 68Ga-DOTA-octreotate (68Ga-DOTATATE) PET/CT underwent serial PET/CT imaging at 30 min, 1 h, 4 h, and 24 h after injection of 64Cu-SARTATE. Adverse reactions were recorded, and laboratory testing was performed during infusion and at 1 and 7 d after imaging. Images were analyzed for lesion and normal-organ uptake and clearance to assess lesion contrast and perform dosimetry estimates. Results:64Cu-SARTATE was well tolerated during infusion and throughout the study, with 3 patients experiencing mild infusion-related events. High lesion uptake and retention were observed at all imaging time-points. There was progressive hepatic clearance over time, providing the highest lesion-to-liver contrast at 24 h. Image quality remained high at this time. Comparison of 64Cu-SARTATE PET/CT obtained at 4 h to 68Ga-DOTATATE PET/CT obtained at 1 h indicated comparable or superior lesion detection in all patients, especially in the liver. As expected, the highest early physiologic organ uptake was in the kidneys, liver, and spleen. Conclusion:64Cu-SARTATE is safe and has excellent imaging characteristics. High late-retention in tumor and clearance from the liver suggest suitability for diagnostic studies and for prospective dosimetry for 67Cu-SARTATE peptide receptor radionuclide therapy, and the half-life of 64Cu would also facilitate good-manufacturing-practice production and distribution to sites without access to 68Ga.

A high-fat diet alters genome-wide DNA methylation and gene expression in SM/J mice.

BACKGROUND: While the genetics of obesity has been well defined, the epigenetics of obesity is poorly understood. Here, we used a genome-wide approach to identify genes with differences in both DNA methylation and expression associated with a high-fat diet in mice. RESULTS: We weaned genetically identical Small (SM/J) mice onto a high-fat or low-fat diet and measured their weights weekly, tested their glucose and insulin tolerance, assessed serum biomarkers, and weighed their organs at necropsy. We measured liver gene expression with RNA-seq (using 21 total libraries, each pooled with 2 mice of the same sex and diet) and DNA methylation with MRE-seq and MeDIP-seq (using 8 total libraries, each pooled with 4 mice of the same sex and diet). There were 4356 genes with expression differences associated with diet, with 184 genes exhibiting a sex-by-diet interaction. Dietary fat dysregulated several pathways, including those involved in cytokine-cytokine receptor interaction, chemokine signaling, and oxidative phosphorylation. Over 7000 genes had differentially methylated regions associated with diet, which occurred in regulatory regions more often than expected by chance. Only 5-10% of differentially methylated regions occurred in differentially expressed genes, however this was more often than expected by chance (p = 2.2 × 10- 8). CONCLUSIONS: Discovering the gene expression and methylation changes associated with a high-fat diet can help to identify new targets for epigenetic therapies and inform about the physiological changes in obesity. Here, we identified numerous genes with altered expression and methylation that are promising candidates for further study.

Is outpatient hysteroscopy the new gold standard? Results from an 11 year prospective observational study.

BACKGROUND: In Australia, gynaecologists continue to investigate women with abnormal bleeding and suspected intrauterine pathology with inpatient hysteroscopy despite some evidence in the literature that that there is no difference in safety and outcome when compared to an outpatient procedure. AIMS: This prospective study assessed the safety, effectiveness and acceptability of outpatient hysteroscopy over 11 years at a tertiary hospital in Australia. Resource savings were then calculated. MATERIALS AND METHODS: A prospective database was analysed from March 2003 to January 2014 (130 months, 990 women). RESULTS: Successful hysteroscopic access was obtained in 94% of cases. Twenty-six percent of patients required a second procedure, including 132 for endometrial polyps and 33 for submucosal fibroids that were not able to be treated in the outpatient setting. On questioning, 88% of women would be happy to have the procedure again. Factors affecting success were pre-procedure pain, menopausal status and previous vaginal delivery. The difference between pain experienced versus pain expected was a major factor in patient acceptability. A vasovagal episode occurred in 5% of cases. CONCLUSION: Outpatient hysteroscopy was demonstrated to be safe, effective and acceptable to women. Provision of an outpatient hysteroscopy service saves theatre time and approximately $1000 per case. Improved techniques and technology will allow progression to a 'see and treat' service, providing further savings. With budget constraints, increasing wait times for major procedures and concerns about trainee surgical experience, an outpatient hysteroscopy service should be considered the 'gold standard' investigation over hysteroscopy in theatre.