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Author(s): Julia F. van der Meulen 1,2,*, Marlies Y. Bongers 1,2, Lisa G. van der Zee 3, Jaklien C. Leemans 1, Ruben G. Duijnhoven 4,5, Robert A. de Leeuw 4, [...], Background Hysteroscopic resection is the first-choice treatment for symptomatic type 0 and 1 fibroids. Traditionally, this was performed under general anesthesia. Over the last decade, surgical procedures are increasingly being performed in an outpatient setting under procedural sedation and analgesia. However, studies evaluating safety and effectiveness of hysteroscopic myomectomy under procedural sedation are lacking. This study aims to investigate whether hysteroscopic myomectomy under procedural sedation and analgesia with propofol is noninferior to hysteroscopic myomectomy under general anesthesia. Methods and findings This was a multicenter, randomized controlled noninferiority trial conducted in 14 university and teaching hospitals in the Netherlands between 2016 and 2021. Inclusion criteria were age [greater than or equal to]18 years, maximum number of 3 type 0 or 1 fibroids, maximum fibroid diameter 3.5 cm, American Society of Anesthesiologists class 1 or 2, and having sufficient knowledge of the Dutch or English language. Women with clotting disorders or with severe anemia (Hb < 5.0 mmol/L) were excluded. Women were randomized using block randomization with variable block sizes of 2, 4, and 6, between hysteroscopic myomectomy under procedural sedation and analgesia (PSA) with propofol or under general anesthesia (GA). Primary outcome was the percentage of complete resections, assessed on transvaginal ultrasonography 6 weeks postoperatively by a sonographer blinded for the treatment arm and surgical outcome. Secondary outcomes were the surgeon&apos;s judgment of completeness of procedure, menstrual blood loss, uterine fibroid related and general quality of life, pain, recovery, hospitalization, complications, and surgical reinterventions. Follow-up period was 1 year. The risk difference between both treatment arms was estimated, and a Farrington-Manning test was used to determine the p-value for noninferiority (noninferiority margin 7.5% of incomplete resections). Data were analyzed according to the intention-to-treat principle, including a per-protocol analysis for the primary outcome. A total of 209 women participated in the study and underwent hysteroscopic myomectomy with PSA (n = 106) or GA (n = 103). Mean age was 45.1 [SD 6.4] years in the PSA group versus 45.0 [7.7] years in the GA group. For 98/106 women in the PSA group and 89/103 women in the GA group, data were available for analysis of the primary outcome. Hysteroscopic resection was complete in 86/98 women (87.8%) in the PSA group and 79/89 women (88.8%) in the GA group (risk difference -1.01%; 95% confidence interval (CI) -10.36 to 8.34; noninferiority, P = 0.09). No serious anesthesiologic complications occurred, and conversion from PSA to GA was not required. During the follow-up period, 15 serious adverse events occurred (overnight admissions). All were unrelated to the intervention studied. Main limitations were the choice of primary outcome and the fact that our study proved to be underpowered. Conclusions Noninferiority of PSA for completeness of resection was not shown, though there were no significant differences in clinical outcomes and quality of life. In this study, hysteroscopic myomectomy for type 0 and 1 fibroids with PSA compared to GA was safe and led to shorter hospitalization. These results can be used for counseling patients by gynecologists and anesthesiologists. Based on these findings, we suggest that hysteroscopic myomectomies can be performed under PSA in an outpatient setting. Trial registration The study was registered prospectively in the Dutch Trial Register (NTR 5357; registration date: 11 August 2015; Date of initial participant enrollment: 18 February 2016).

Objective: To evaluate whether physical function and quality of life was influenced by discharge on the same‐day after a total laparoscopic hysterectomy. Design: Multicentre non‐inferiority randomised controlled trial. Setting: Five teaching hospitals and two university hospitals in the Netherlands. Population: Patients undergoing laparoscopic hysterectomy for benign or premalignant disease. Methods: Following informed consent, participants were allocated 1:1 either to same‐day discharge (SDD) or next‐day discharge (NDD). Main Outcome Measures: The primary outcome was physical function at 7 days after surgery measured by the Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function short Form 10A. Secondary outcomes were physical function and quality of life at 1 and 3 days and 6 weeks after surgery measured with PROMIS short Form 10A and the EuroQol questionnaire (EQ‐5D‐5L). Results: Two hundred and five patients were included of whom 105 were allocated to SDD and 100 to NDD. Physical function 7 days after surgery was 35.95 in the SDD group and 35.63 in the control group (mean difference 0.32; 95% CI [0.07–0.57]). As the upper limit of the 95% CI does not exceed the non‐inferiority margin of 4 points, non‐inferiority of SDD could be demonstrated. No difference in physical function nor quality of life on Days 1 and 3 and 6 weeks could be found. Conclusion: This research demonstrates same‐day discharge after laparoscopic hysterectomy is non‐inferior to next day discharge in physical function 7 days after surgery. [ABSTRACT FROM AUTHOR]

Introduction: Increasing evidence shows that conservative management of ovarian tumors classified as benign, based on ultrasound assessment, is safe. Therefore, conservative management has been adopted as the preferred strategy for certain ovarian tumors assessed as benign in the Dutch national guideline on enlarged ovaries in 2013. The aim of this study was to examine whether implementation of this guideline has led to changes in the number of women/100 000 women undergoing surgery for an ovarian tumor in the Netherlands. Material and Methods: Histopathology reports were requested for all examinations of ovarian and fallopian tube specimens (including cyst enucleations) registered in Palga, the Dutch nationwide pathology databank, from 2011 (before guideline adaptation) and 2019 (after guideline adaptation). Reports on prophylactically removed adnexa, removal for other primary tumors (eg endometrial carcinoma), and for patients under 18 years of age, were excluded from the analysis. Interobserver agreement for the inclusion and classification of reports was assessed using Cohen's Kappa analysis. Results: A total of 34 932 reports were retrieved, 13 917 of which were included in the analysis. In 2011 and 2019, respectively, 96.3/100 000 vs 68.8/100 000 women aged ≥18 underwent surgery for benign ovarian tumors, and 19.6/100 000 vs 18.3/100 000 for borderline and malignant tumors combined. The number of women/100 000 who had surgery for a benign ovarian tumor per 100 000 women declined by 28.5% (p < 0.001) between 2011 and 2019. The largest difference between 2011 and 2019 was observed in the number of women per 100 000 women who underwent surgery for a serous cystadenoma (−40.7%; 20.8/100 000 vs. 12.3/100 000), followed by endometrioma (−33.2%; 14.7/100 000 vs. 9.8/100 000), simple epithelial cyst (−57.3%; 8.4/100 000 vs. 3.6/100 000), and corpus luteum cyst (−57.0%; 4.0/100 000 vs. 1.7/100 000). Cohen's Kappa for the interobserver agreement was 0.96. Conclusions: The number of women/100 000 undergoing surgery for a benign ovarian tumor has substantially decreased in the Netherlands when comparing data before and after implementation of the national guideline in 2013, while the number of women/100 000 undergoing surgery for a malignant or borderline tumor remained the same. These findings suggest successful implementation of the updated guideline, and a measurable effect on increased adoption of conservative management for benign‐looking ovarian tumors. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease often leads to kidney dysfunction due to renal fibrosis, regardless of the initial cause of kidney damage. Macrophages are crucial players in the progression of renal fibrosis as they stimulate inflammation, activate fibroblasts, and contribute to extracellular matrix deposition, influenced by their metabolic state. Nucleotide-binding domain and LRR-containing protein X (NLRX1) is an innate immune receptor independent of inflammasomes and is found in mitochondria, and it plays a role in immune responses and cell metabolism. The specific impact of NLRX1 on macrophages and its involvement in renal fibrosis is not fully understood. Methods: To explore the specific role of NLRX1 in macrophages, bone-marrow-derived macrophages (BMDMs) extracted from wild-type (WT) and NLRX1 knockout (KO) mice were stimulated with pro-inflammatory and pro-fibrotic factors to induce M1 and M2 polarization in vitro. The expression levels of macrophage polarization markers (Nos2, Mgl1, Arg1, and Mrc1), as well as the secretion of transforming growth factor β (TGFβ), were measured using RT-PCR and ELISA. Seahorse-based bioenergetics analysis was used to assess mitochondrial respiration in naïve and polarized BMDMs obtained from WT and NLRX1 KO mice. In vivo, WT and NLRX1 KO mice were subjected to unilateral ureter obstruction (UUO) surgery to induce renal fibrosis. Kidney injury, macrophage phenotypic profile, and fibrosis markers were assessed using RT-PCR. Histological staining (PASD and Sirius red) was used to quantify kidney injury and fibrosis. Results: Compared to the WT group, an increased gene expression of M2 markers—including Mgl1 and Mrc1—and enhanced TGFβ secretion were found in naïve BMDMs extracted from NLRX1 KO mice, indicating functional polarization towards the pro-fibrotic M2 subtype. NLRX1 KO naïve macrophages also showed a significantly enhanced oxygen consumption rate compared to WT cells and increased basal respiration and maximal respiration capacities that equal the level of M2-polarized macrophages. In vivo, we found that NLRX1 KO mice presented enhanced M2 polarization markers together with enhanced tubular injury and fibrosis demonstrated by augmented TGFβ levels, fibronectin, and collagen accumulation. Conclusions: Our findings highlight the unique role of NLRX1 in regulating the metabolism and function of macrophages, ultimately protecting against excessive renal injury and fibrosis in UUO. [ABSTRACT FROM AUTHOR]