DNA alterations in ovarian adult granulosa cell tumours: A scoping review protocol.

BACKGROUND: Identifying and describing molecular alterations in tumors has become common with the development of high-throughput sequencing. However, DNA sequencing in rare tumors, such as ovarian adult granulosa cell tumor (aGCT), often lacks statistical power due to the limited number of cases in each study. Questions regarding personalized treatment or prognostic biomarkers for recurrence or other malignancies therefore still need to be elucidated. This scoping review protocol aims to systematically map the current evidence and identify knowledge gaps regarding DNA alterations, actionable variations and prognostic biomarkers in aGCT. METHODS: This scoping review will be conducted based on Arksey and O'Malley's methodological framework and later modifications by JBI Evidence Synthesis. The protocol complies with Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. All original publications describing molecular alterations of aGCT will be included. The search will be performed in May 2024 in the following databases: MEDLINE (Ovid), Embase (Ovid), Web of Science Core Collection and Google Scholar (100-top ranked). DISCUSSION: This scoping review will identify knowledge and gaps in the current understanding of the molecular landscape of aGCT, clinical trials on actionable variations and priorities for future research. As aGCT are rare, a possible limitation will be the small sample sizes and heterogenic study settings. SCOPING REVIEW REGISTRATION: The review protocol is registered at Open Science Framework under https://doi.org/10.17605/OSF.IO/PX4MF.

Effect of 24 mg dexamethasone preoperatively on surgical stress, pain and recovery in robotic-assisted laparoscopic hysterectomy.

Background: Robotic-assisted hysterectomy is an alternative to laparoscopic surgery as part of a minimal invasive regimen. Several treatment strategies are followed to improve the overall outcome and minimize surgical stress. Glucocorticoids provide significant analgesic and antiemetic effects but their role in reducing inflammatory stress in a fast-track, multi-modal setting in patients undergoing minimally invasive surgery remains to be investigated in details. Methods: This study will evaluate in a randomized trial the effect of a single dose of 24 mg dexamethasone on 100 women undergoing robotic-assisted hysterectomy with regard to surgical stress, measured by c-reactive protein as primary outcome and, further, other stress markers like white blood cell subtypes. The postoperative recovery will be registered in validated charts and questionnaires for pain and analgesic use, quality of recovery, incontinence, sexual and work life. Furthermore, in a sub-analysis, transcriptional profiling will be performed to explore the mechanism of systemic innate and adaptive immune system perturbation induced by surgical stress. Conclusion: The study will provide solid evidence on markers of immunomodulation biomarkers and in addition the subjective effects and underlying mechanisms of perioperative glucocorticoid in women undergoing robotic hysterectomy. These include important aspects of life quality like pain, fatigue, freedom of medications, resuming work and sexual activities.

Diabetes risk after a normal oral glucose tolerance test during pregnancy.

INTRODUCTION: Our aim was to conduct a follow-up of a cohort of women screened for GDM with a normal oral glucose tolerance test (OGTT) during pregnancy to investigate the incidence and time of diagnosis of manifest diabetes mellitus and identify risk factors for subsequent development of diabetes. METHODS: This was a follow-up study of a cohort with normal and borderline OGTT in 1991/1992. Among the original 352 women, only five were lost to follow-up. RESULTS: In total, 64 women (18%) had manifest diabetes. Their median age was 57 years after 28 years of follow-up. This amounts to three times the expected rate compared with the background population. The rate of manifest diabetes rises 10-20 years after pregnancy and after the age of 40 years. A normal fasting glucose and also a borderline fasting glucose at OGTT during pregnancy were associated with an increased risk of manifest diabetes (p less-than 0.001), also after adjustment for age, Body Mass Index, non-Danish origin and smoking during pregnancy (p less-than 0.002). CONCLUSION: The incidence of diabetes is higher in women with various risk factors for DM and a previously normal OGTT in pregnancy than in the background population. Our results are useful in identifying the time during which women may benefit from effective implementation of evidence-based treatment to postpone and avert manifest DM, even though they had a normal OGTT during pregnancy. FUNDING: none. TRIAL REGISTRATION: The trial was registered with the the Regional Ethics Committee and the Data Protection Agency, nos. 2014-41-3433, 1-16-02-824-17 (under running permission no. 621549), 1-16-02-825-17, and 1-16-02-180-17, all under the cover of data handling agreement no. 509 with the Danish Health Authority.

Metabolic syndrome in women with previous gestational diabetes.

To evaluate the incidence and timing of the diagnosis of metabolic syndrome in a cohort of Danish women after a pregnancy with gestational diabetes (GDM) to estimate the optimum time for preventative actions in relation to metabolic syndrome (MetS). In this follow-up study, 435 women were included from a consecutive cohort with prior history of GDM. Data on dyslipidemia, hypertension and other cardiovascular disorders (CVD) were extracted from the electronic patient journal. Any antidiabetic, cardiovascular and cholesterol-lowering medicine was ascertained in the national prescription database. Similarly, any blood test taken was evaluated. We defined a patient having MetS if the criteria of the WHO based definition of diabetes or impaired glucose regulation were met. Further, we added as alternative for glucose intolerance, a glycosylated hemoglobin (HbA1c) > 44 mmol/mol or the former level ≥ 6.5%. Further, dyslipidemia, lipid lowering medications, BMI > 30 kg/m2 or antihypertensive treatment were used. For MetS outcome, diagnosis or medication for CVD was registered. All women were followed for median 5.7 years (range 0; 9). The incidence of MetS was 28%. Thirteen percent of these qualified already within one year after pregnancy for the diagnosis of MetS. Postpartum MetS was detected after a median of 3 years (range 0; 7 years); further, 36 (8%) had been diagnosed with manifest diabetes after pregnancy. The diagnosis of postpartum MetS was strongly associated with the prevalence of manifest diabetes. Six years after pregnancy the rate of metabolic syndrome was more than tripled (25 vs. 89%, no DM vs manifest DM, RR: 6.7; 95% CI 2.7-17, p < 0.001). At 40 years the MetS rate nearly tripled if manifest DM was diagnosed (26 vs. 78%, no DM vs. manifest DM, RR: 3.3, 95% CI 1.8-6, p < 0.001). We found that GDM and later on manifest DM in women increase the risk of metabolic syndrome. There seems to be a window of opportunity before the early thirties where it would be especially beneficial to begin preventive efforts in women with GDM.