Comparison Between Sonography-Based and Surgical Evaluation of Endometriotic Lesions Using the #Enzian Classification - A Retrospective Data Analysis.

PURPOSE: To compare the location and sizes of deep endometriosis (DE) lesions evaluated by preoperative transvaginal sonography (TVS) in different #Enzian compartments with intraoperatively assessed DE location and size. MATERIALS AND METHODS: Retrospective data analysis of 93 women undergoing TVS and surgery for DE in 2019 at a tertiary referral center for endometriosis. RESULTS: #Enzian compartment C (rectum) showed the highest rate of exact concordance with 74% of cases, which increased to 87% when a tolerance margin of a maximum of 3mm for TVS measurements was taken into account. For compartment B (uterosacral ligaments, parametria) and compartment A (vagina, rectovaginal space), the rates of exact concordance were slightly lower. In compartment O (ovary), high exact concordance rates similar to those observed for compartment C were observed. In compartment T (tubo-ovarian unit), most reliable estimations were seen for slight (TVS T1) and severe adhesions (TVS T3). There were only a few cases of missed lesions as well as false positives on TVS: Sensitivity was 100% for all compartments except for A and B left (97%) and FB (urinary bladder, 86%); specificity was 100% for FB, FI (other intestinal locations), FU (ureters) and O right, 86%-98% for A, B right, C, O left and FO (other extragenital lesions) and 70% for B left. CONCLUSION: The preoperative evaluation of the location and size of DE lesions by TVS in different #Enzian compartments is accurate, providing a detailed presurgical description of the extent of ovarian and deep endometriosis and associated minor or severe adhesions.

Differences in intensity and quality of bowel symptoms in patients with colorectal endometriosis : An observational cross-sectional study.

BACKGROUND: Patients suffering from colorectal deep endometriosis (DE) experience gastrointestinal symptoms with almost the same frequency as gynecological pain symptoms. Preoperatively existing gastrointestinal symptoms may translate into pathological gastrointestinal quality of life index (GIQLI) and low anterior resection syndrome scores (LARS). This prospective questionnaire-based case control study aims to assess the prevalence of gastrointestinal complaints reflected by changes in LARS and GIQLI scores in patients with colorectal deep endometriosis prior to surgical treatment and compare those to a healthy control group. METHODS: The study was conducted at the Hospital St. John of God in Vienna and included a total of 97 patients with histologically confirmed colorectal DE with radical surgical treatment and 96 women in whom DE was excluded via transvaginal sonography (TVS) or visually. Gastrointestinal symptoms reflected by LARS and GIQLI scores were evaluated presurgically and in controls. RESULTS: A total of 193 premenopausal patients were included in this study. A mean GIQLI of 90.7 ± 22.0 and 129.4 ± 11.1 was observed among patients and controls, respectively, showing a significantly higher morbidity concerning gastrointestinal symptoms and decreased quality of life (QoL) compared to healthy controls (p < 0.001). The LARS score results demonstrated that 18.6% of the patients with bowel DE presented with a major LARS and 27.8% with a minor LARS presurgically compared to 2.1% and 9.4% of control patients, respectively (p < 0.001). CONCLUSION: Patients with colorectal DE experience a quality of gastrointestinal symptoms translating into a decreased QoL and pathological GIQLI and LARS scores already presurgically. As a consequence, these instruments should be interpreted with caution.

Comparison of #Enzian classification and revised American Society for Reproductive Medicine stages for the description of disease extent in women with deep endometriosis.

STUDY QUESTION: How is endometriosis extent described by the #Enzian classification compared to the revised American Society for Reproductive Medicine (rASRM) stages in women undergoing radical surgery for deep endometriosis (DE)? SUMMARY ANSWER: The prevalence and severity grade of endometriotic lesions and adhesions as well as the total number of #Enzian compartments affected by DE increase on average with increasing rASRM stage; however, DE lesions are also present in rASRM stages 1 and 2, leading to an underestimation of disease severity when using the rASRM classification. WHAT IS KNOWN ALREADY: Endometriotic lesions can be accurately described regarding their localization and severity by sonography as well as during surgery using the recently updated #Enzian classification for endometriosis. STUDY DESIGN, SIZE, DURATION: This was a prospective multicenter study including a total of 735 women between January 2020 and May 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Disease extent in women undergoing radical surgery for DE at tertiary referral centers for endometriosis was intraoperatively described using the #Enzian and the rASRM classification. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 735 women were included in the study. Out of 31 women with rASRM stage 1, which is defined as only minimal disease, 65% (i.e. 20 women) exhibited DE in #Enzian compartment B (uterosacral ligaments/parametria), 45% (14 women) exhibited DE in #Enzian compartment A (vagina/rectovaginal septum) and 26% (8 women) exhibited DE in #Enzian compartment C (rectum). On average, there was a progressive increase from rASRM stages 1-4 in the prevalence and severity grade of DE lesions (i.e. lesions in #Enzian compartments A, B, C, FB (urinary bladder), FU (ureters), FI (other intestinal locations), FO (other extragenital locations)), as well as of endometriotic lesions and adhesions in #Enzian compartments P (peritoneum), O (ovaries) and T (tubo-ovarian unit). In addition, the total number of #Enzian compartments affected by DE lesions on average progressively increased from rASRM stages 1-4, with a maximum of six affected compartments in rASRM stage 4 patients. LIMITATIONS, REASONS FOR CAUTION: Interobserver variability may represent a possible limitation of this study. WIDER IMPLICATIONS OF THE FINDINGS: The #Enzian classification includes the evaluation of DE in addition to the assessment of endometriotic lesions and adhesions of the ovaries and tubes and may therefore provide a comprehensive description of disease localization and extent in women with DE. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for this study. All authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Rates of severe complications in patients undergoing colorectal surgery for deep endometriosis-a retrospective multicenter observational study.

INTRODUCTION: Surgical experience and hospital procedure volumes have been associated with the risk of severe complications in expert centers for endometriosis in France. However, little is known about other certified units in Central European countries. MATERIAL AND METHODS: This retrospective observational study included 937 women who underwent surgery for colorectal endometriosis between January 2018 and January 2020 in 19 participating expert centers for endometriosis. All women underwent complete excision of colorectal endometriosis by rectal shaving, discoid or segmental resection. Postoperative severe complications were defined as grades III-IV of the Clavien-Dindo classification system including anastomotic leakage, fistula, pelvic abscess and hematoma. Surgical outcomes of centers performing less than 40 (group 1), 40-59 (group 2) and ≥60 procedures (group 3) over a period of 2 years were compared. RESULTS: The overall complication rate of grade III and IV complications was 5.1% (48/937), with rates of anastomotic leakage, fistula formation, abscess and hemorrhage in segmental resection, discoid resection and rectal shaving, respectively, as follows: anastomotic leakage 3.6% (14/387), 1.4% (3/222), 0.6% (2/328); fistula formation 1.6% (6/387), 0.5% (1/222), 0.9%; (3/328); abscess 0.5% (2/387), 0% (0/222) and 0.6% (2/328); hemorrhage 2.1% (8/387), 0.9% (2/222) and 1.5% (5/328). Higher overall complication rates were observed for segmental resection (30/387, 7.8%) than for discoid (6/222, 2.7%, P = 0.015) or shaving procedures (12/328, 3.7%, P = 0.089). No significant correlation was observed between the number of procedures performed and overall complication rates (rSpearman  = -0.115; P = 0.639) with a high variability of complications in low-volume centers (group 1). However, an intergroup comparison revealed a significantly lower overall severe complication rate in group 3 than in group 2 (2.9% vs 6.9%; P = 0.017) without significant differences between other groups. CONCLUSIONS: A high variability in complication rates does exist in centers with a low volume of activity. Major complications may decrease with an increase in the volume of activity but this effect cannot be generally applied to all institutions and settings.

Serial assessment of inflammatory parameters for prediction of septic complications following surgery for colorectal endometriosis : A descriptive, retrospective study.

PURPOSE: To assess whether C­reactive protein (CRP), white blood cell count (WBC) and body temperature changes are suitable parameters for the early detection of septic complications following resection of colorectal deep endometriosis (DE). METHODS: Retrospective data analysis of CRP, WBC and body temperature courses following colorectal surgery for DE at a tertiary referral center for endometriosis. RESULTS: Out of 183 surgeries performed, 10 major surgical complications were observed, including 4 anastomotic leakages (AL 2%) and 2 rectovaginal fistulae (RVF 1%). In the presence of a lower gastrointestinal tract (GIT)-related septic complication or abdominal wall abscess, serum CRP levels were increased starting at postoperative day 2-3. A cut-off value of 10 mg/dl on day 4 for prediction of early septic complications could be verified (area under the curve 0.94, obtained by receiver operating characteristics analysis, sensitivity 88%, specificity 90%, positive predictive value 32%, negative predictive value 99%). Additionally, most patients with early septic complications exhibited increased WBC levels starting mainly from day 3-4; however, increased inflammatory parameters could not be observed in one patient with an RVF. Body temperature did not prove useful for early discrimination between uncomplicated cases and those with early septic complications. CONCLUSION: Relevant elevations of serum CRP and WBC levels were demonstrated in patients with early septic complications following surgery for colorectal DE starting at postoperative day 2-4. The cut-off value of 10 mg/dl for CRP levels may serve as an early predictor for lower GIT-related septic complications but should be used with caution in women with suspected RVF development.

Comparison between Sonography-based and Surgical Extent of Deep Endometriosis Using the Enzian Classification - A Prospective Diagnostic Accuracy Study.

STUDY OBJECTIVE: To compare a preoperative evaluation of deep endometriosis (DE) by transvaginal sonography (TVS) according to the Enzian classification with the intraoperatively assessed extent of DE using the Enzian system. DESIGN: Prospective diagnostic accuracy study. SETTING: Tertiary referral center for endometriosis. PATIENTS: Women undergoing TVS and surgery for DE between 2017 and 2019 (N = 195). INTERVENTIONS: Evaluation of DE lesion sizes according to the Enzian classification as evaluated by preoperative TVS compared with surgical findings. MEASUREMENTS AND MAIN RESULTS: The rate of exact concordances between preoperative TVS-based predictions of DE lesion sizes and intraoperatively assessed lesion sizes according to the Enzian classification varied depending on anatomic localizations, that is, Enzian compartments, and evaluated lesion size. The highest rate of exact concordances was found in Enzian compartment C (rectosigmoid) in which 86% of all TVS C3 lesions were confirmed as such at surgery. Enzian compartment A (vagina, rectovaginal septum) showed similar results. The rates of exact concordances were slightly lower in Enzian compartment B (uterosacral ligaments, parametria), with confirmation at surgery of 71% of TVS B2 lesions. In most cases of discordant findings, an underestimation of the lesion size by 1 severity grade was observed compared with the intraoperative findings. In Enzian compartment FB (urinary bladder), 91% of the lesions seen at TVS and 98% of cases without any lesion at TVS were confirmed surgically. TVS could detect DE preoperatively in compartments A, B, C, and FB with an overall sensitivity of 84%, 91%, 92%, and 88%, respectively, and a specificity of 85%, 73%, 95%, and 99%, respectively. CONCLUSION: TVS provides a valuable preoperative estimation of DE localization and lesion size using the Enzian classification, especially for Enzian compartments A, C, and FB. For Enzian compartment B, the exact assessment of the lesion size using the Enzian system seems to be less precise than for the other compartments.

Transvaginal Sonographic Imaging and Associated Techniques for Diagnosis of Ovarian, Deep Endometriosis, and Adenomyosis: A Comprehensive Review.

Imaging of endometriosis and in particular deep endometriosis (DE) is crucial in the clinical management of women facing this debilitating condition. Transvaginal sonography (TVS) is the first-line imaging method and magnetic resonance imaging (MRI) may provide supplemental information. However, the delay in diagnosis of up to 10 years and more is of concern. This problem might be overcome by simple steps using imaging with emphasis on TVS and referral to tertiary care. Finally, TVS is crucial in mapping extent and location of disease in planning surgical therapy and counseling women regarding various therapeutic options. This review presents the available data on imaging of endometriosis with a focus on TVS and MRI for DE, adenomyosis, and ovarian endometriomas including endometriomas in pregnancy as well as the use of "soft markers." The review presents an approach that is in accordance with the International Deep Endometriosis Analysis (IDEA) group consensus statement.

Basic Laparoscopic Skills Training Is Equally Effective Using 2D Compared to 3D Visualization: A Randomized Controlled Trial.

Reduced depth perception due to two-dimensional (2D) visualization of a three-dimensional (3D) space represents a main challenge in acquiring basic laparoscopic skills (BLS); 3D visualization might increase training efficiency. This study aimed to assess whether BLS training on a standard box trainer using 2D is at least equally effective compared to 3D. Medical students were randomized to training of Fundamentals of Laparoscopic Surgery (FLS) tasks using either 2D or 3D for four weeks. Baseline and post-training tests were performed using the assigned visualization modality. Data of 31 participants were analyzed (n = 16 2D, n = 15 3D). Baseline test scores did not differ significantly between groups; only at the peg transfer task and total scores, the 3D group performed better than the 2D group. All scores improved significantly in both groups, with post training scores not differing significantly between groups. Non-inferiority of 2D compared to 3D was demonstrated for total score improvement and improvement in all individual FLS tasks except for suturing with extracorporeal knot tying. Post training test performance did not change significantly when changing to the unfamiliar modality. In conclusion, BLS training using standard 2D is at least equally effective as with 3D, without significant disadvantages when changing to the other modality.

Dynamics of soluble syndecan-1 in maternal serum during and after pregnancies complicated by preeclampsia: a nested case control study.

Background We investigated the dynamics and the predictive value of soluble syndecan-1 (Sdc-1), a biomarker of endothelial dysfunction, in uneventful pregnancies and pregnancies complicated by preeclampsia (PE). Methods Serum levels of Sdc-1 were measured at sequential time points during and after uneventful pregnancies (control, n = 95) and pregnancies developing PE (PE_long, n = 12). Levels were further measured in women with symptomatic PE (PE_state, n = 46) at a single time point. Results Sdc-1 levels increased consistently throughout pregnancy. In the PE_long group Sdc-1 levels were lower at all visits throughout pregnancy, and reached significance in weeks 18-22 (p = 0.019), 23-27 (p = 0.009), 28-32 (p = 0.006) and 33-36 (p = 0.008). After delivery, Sdc-1 levels dropped sharply in all pregnancies but were significantly elevated in the PE_long group. The predictive power of Sdc-1 was evaluated analyzing receiver operating characteristic (ROC) curves. A significant power was reached at weeks 14-17 (area under the curve [AUC] 0.65, p = 0.025), 23-27 (AUC 0.73, p = 0.004) and 33-36 (AUC 0.75, p = 0.013). Conclusions In summary, Sdc-1 levels were lower in women developing PE compared to uneventful pregnancies and Sdc-1 might be useful to predict PE. After delivery, Sdc-1 levels remained higher in women with PE. Additional studies investigating the link between glycocalyx degradation, Sdc-1 levels and placental and endothelial dysfunction in pregnancies affected by PE are warranted.

Association between disease extent and pain symptoms in patients with deep infiltrating endometriosis.

RESEARCH QUESTION: The study aimed to assess the associations between pre-operative symptoms in patients with deep infiltrating endometriosis (DIE) and intraoperatively determined extent of disease as described by the revised ENZIAN score. DESIGN: This was a retrospective data analysis of women who underwent surgery for DIE between 2014 and 2018 at the Department of Gynecology, Hospital St. John of God, Vienna (a tertiary referral centre for endometriosis). RESULTS: Data from 245 women were analysed. Statistically significant associations were found between involvement of ENZIAN compartment B (uterosacral ligaments, parametrium) and presence of dyspareunia (P = 0.002), ENZIAN compartment C (rectum, sigmoid colon) and dyschezia (P < 0.001), and ENZIAN compartment FB (urinary bladder) and dysuria (P < 0.001, Fisher's exact test). Statistically significant correlations were also detected between symptom severity of dyschezia and lesion size in ENZIAN compartment C (rs = 0.334, P < 0.001), and severity of dyspareunia and lesion size in ENZIAN compartment B (rs = 0.127, P = 0.046). Severity of dysmenorrhoea was correlated with lesion size in ENZIAN compartment A (rs = 0.244, P < 0.001) and was associated with the presence of adenomyosis (compartment FA; P = 0.005, Mann-Whitney U-test). Additionally, the number of affected compartments (A, B, C and FA) correlated with the severity of dysmenorrhoea (rs = 0.256, P < 0.001) and dyschezia (rs = 0.161, P = 0.012). CONCLUSION: In contrast to previous studies evaluating disease extent based on the revised American Society for Reproductive Medicine (rASRM) score, disease localization and extent as described by the revised ENZIAN score was associated and correlated with the presence and severity of different pre-operative symptoms. These explorative findings suggest that it may be important to evaluate the extent of DIE using the revised ENZIAN score in addition to the rASRM score.

Influence of training level on cervical cone size and resection margin status at conization: a retrospective study.

OBJECTIVE: To explore whether a surgeon's training level influences the rate of incomplete resections or the amount of resected cervical tissue in women treated with large loop excision of the transformation zone (LLETZ). METHODS: The present study is a retrospective analysis of the data of women who had undergone LLETZ for cervical intraepithelial neoplasia (CIN) within the years 2004-2008 at the Medical University of Vienna. Women were grouped according to the level of training of the operating surgeon (i.e, resident or staff gynecologist) and univariate and multivariable analyses were performed to identify independent risk factors for excessive cone volume, depth and incomplete resection (i.e., positive resection margin). RESULTS: Data of 912 women were analysed. Residents had a significantly larger cone volume [median 2681 (interquartile range 1472-4109) mm3] than staff gynecologists [2094 (1309-3402) mm3] (p = 0.001) in univariate analysis. The depth of resection and the rate of incomplete resection were comparable between both groups. In a binary logistic multivariable analysis, the level of training as well as patient's age was significantly associated with a cone volume larger than 2500 mm3. CONCLUSION: Conization performed by residents as opposed to staff gynecologists does not compromise the procedure's effectiveness but may expose women to a potential additional risk for adverse obstetrical outcomes due to excessive resection of cervical tissue.

Management of uterine ectopic pregnancy - local vs. systemic methotrexate.

INTRODUCTION: The aim of this study was to compare ultrasound-guided local methotrexate (MTX) vs. systemic methotrexate in uterine ectopic pregnancy regarding the beta human chorionic gonadotropin (hCG) clearance duration. MATERIAL AND METHODS: Patients with interstitial pregnancy, cervical pregnancy or cesarean scar pregnancy were included. Methotrexate was administered locally ultrasound-guided (25 mg methotrexate fixed dose) or systemically (intramuscular; 50 mg/m2 body weight). Beta hCG clearance duration in days formed the main outcome measure. RESULTS: Forty-six patients with uterine ectopic pregnancy were included. The mean estimated beta hCG clearance duration was 29.2 days longer in patients with local methotrexate compared with systemic methotrexate (64.7 vs. 31.5 days, respectively; p = 0.026). There was no significant difference between local vs. systemic methotrexate regarding adverse events such as bleeding (p = 0.376), pain (p = 0.146) or secondary surgery (p = 0.631). There was no association of initial beta hCG levels (p = 0.746), initial progesterone levels (p = 0.870) or patients' age (p = 0.604) and the beta hCG clearance duration. No significant difference in beta hCG clearance duration comparing local methotrexate injection with aspiration vs. local methotrexate injection without aspiration could be found (mean 49.4 and 71.6 days, respectively, p = 0.225). CONCLUSIONS: In patients with uterine ectopic pregnancies, the mean estimated beta hCG clearance duration was 29.2 days longer when applying local methotrexate compared with systemic methotrexate.

Dynamics of serum C-type natriuretic peptide as predictor for preeclampsia.

OBJECTIVE: To evaluate serum levels of the amino-terminal propeptide of C-type natriuretic peptide (NTproCNP) in uneventful pregnancies and pregnancies complicated by preeclampsia (PE) and NTproCNP's accuracy for prediction of PE. STUDY DESIGN: Nested case control pilot study including women with uneventful pregnancy (Control, n = 100) and asymptomatic women who later developed PE (PE_long, n = 12). NTproCNP levels were measured in a maximum of ten sequential blood samples per patient (seven visits during pregnancy, three afterwards), which had been collected prospectively. RESULTS: In controls, NTproCNP decreased from weeks 11-13 on, reaching a nadir at the end of the second trimester (weeks 23-27), and subsequently reached the highest levels at the end of pregnancy. In comparison, the PE_long group showed a significantly different NTproCNP course (p = .042), including significantly elevated levels in weeks 18-22 (p = .034) and 23-27 (p = .016). Significant predictive power of single time point measurements of NTproCNP for predicting short-term occurrence of preeclampsia in asymptomatic women was found in weeks 28-32 (p = .023) and 33-36 (p = .014). Furthermore, an increase > -0.038 pmol/l per week between weeks 11-13 and 14-17 was also predictive for PE (area under the curve, AUC: 0.75; p < .001; sensitivity: 90%; specificity: 60%), as was an increase of > 0.084 pmol/l per week between weeks 11-13 and 18-22 (AUC: 0.69, p = .048; sensitivity: 55%; specificity: 88%). CONCLUSIONS: Measurement of NTproCNP in pregnancy might be useful to increase diagnostic awareness in women who will develop PE.

Comparing two Uterine Manipulators During Total Laparoscopic Hysterectomy: A Randomized Controlled Trial.

STUDY OBJECTIVE: To compare 2 different types of uterine manipulators (i.e., tight fitting vs loose fitting) used for total laparoscopic hysterectomy (TLH). DESIGN: A randomized controlled trial. The primary end points were time for colpotomy, time from skin incision to detachment of the uterus, and histologic assessment of thermal damage to the vagina (Canadian Task Force classification I). SETTING: A university teaching hospital. PATIENTS: All consecutive women scheduled for TLH from May 2014 to December 2015. Patients were excluded if pregnancy or malignancy was suspected or uterine size exceeded 20 weeks' gestation. INTERVENTIONS: Patients were randomized to undergo TLH with 1 of the following uterine manipulators: (1) Colpo-Probe Vaginal Fornix Delineator (Cooper Surgical, Inc, Trumbull, CT) or (2) Hohl manipulator (KARL STORZ AG, Tuttlingen, Germany). MEASUREMENTS AND MAIN RESULTS: A total of 91 patients, 49 in the Hohl manipulator group and 42 in the Colpo-Probe group, were included in the final analysis. There was no difference in patient characteristics, uterine weight, or estimated blood loss. The median time for insertion of the manipulator (2 minutes [interquartile range (IQR), 2-5 minutes] vs 6 minutes [IQR, 5-7], p < .001), the median time from skin incision to detachment of the uterus (55 minutes [IQR, 41-70] vs 65 minutes [IQR, 58-79], p = .004), and the median time for colpotomy (7 minutes [IQR, 5-10] vs 12 [IQR, 8-17], p < .001) were shorter with the Hohl manipulator. Thermal damage to the vagina varied greatly and ranged from 32 µm to 5232 µm but was not significantly different between groups (median maximum thermal damage = 1043 µm [IQR, 682-1934] vs 1522 µm [IQR, 884-2144], p = .211). CONCLUSION: Use of the Hohl manipulator results in a shorter operative time from skin incision to detachment of the uterus during TLH. Although the colpotomy time is shorter using the Hohl manipulator, this did not translate to less thermal damage to the vaginal cuff. Further studies comparing uterine manipulators are warranted to find the optimal instrument for ease of surgery and decreased thermal spread.

Training on an inexpensive tablet-based device is equally effective as on a standard laparoscopic box trainer: A randomized controlled trial.

BACKGROUND: The aim of the study was to assess whether an inexpensive tablet-based box trainer (TBT) is at least equally effective compared with a standard box trainer (SBT) to learn basic laparoscopic skills (BLS). BLS training outside the operating room has been shown to be beneficial for surgical residency. However, simulation trainers are expensive and are not consistently available in all training centers. Therefore, TBT and other homemade box trainers were developed. METHODS: Medical students were randomized to either a TBT or an SBT and trained 4 fundamentals of laparoscopic surgery (FLS) tasks for 1 hour twice a week for 4 weeks. A baseline test before the training period and a posttraining test were performed. All students then completed a questionnaire to assess their assigned box trainer. The primary outcome measure was the improvement in total test scores. Improvement in the scores for the 4 individual FLS tasks was chosen as a secondary outcome measure. RESULTS: Thirty-two medical students were recruited. Baseline test scores did not differ significantly between the groups. BLS improved significantly in both groups for the total score and for all 4 tasks separately. Participants in the TBT group showed a greater improvement of total scores than those in the SBT group, although this did not reach statistical significance; noninferiority of the TBT compared with the SBT concerning the improvement of total scores could be demonstrated. Regarding the individual FLS tasks, noninferiority of the TBT could be shown for the pattern cutting and the suturing with intracorporeal knot-tying task. The acceptance of the TBT by the trainees was very good. CONCLUSION: Learning BLS on a homemade TBT is at least equally effective as on an SBT, with the advantage of being very cost saving. Therefore, this readily available box trainer may be used as an effective, flexible training device outside the operating room to improve accessibility to simulation training.

Interleukin-33 stimulates GM-CSF and M-CSF production by human endothelial cells.

Interleukin (IL)-33, a member of the IL-1 family of cytokines, is involved in various inflammatory conditions targeting amongst other cells the endothelium. Besides regulating the maturation and functions of myeloid cells, granulocyte macrophage-colony stimulating factor (GM-CSF) and macrophage-CSF (M-CSF) have been shown to play a role in such pathologies too. It was the aim of our study to investigate a possible influence of IL-33 on GM-CSF and M-CSF production by human endothelial cells. IL-33, but not IL-18 or IL-37, stimulated GM-CSF and M-CSF mRNA expression and protein production by human umbilical vein endothelial cells (HUVECs) and human coronary artery ECs (HCAECs) through the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway in an IL-1-independent way. This effect was inhibited by the soluble form of ST2 (sST2), which is known to act as a decoy receptor for IL-33. The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor fluvastatin could also be shown to moderately reduce the IL-33-mediated effect on M-CSF, but not on GM-CSF expression. In addition, IL-33, IL-1ß, GM-CSF and M-CSF were detected in endothelial cells of human carotid atherosclerotic plaques using immunofluorescence. Upregulation of GM-CSF and M-CSF production by human endothelial cells, an effect that appears to be mediated by NF-κB and to be independent of IL-1, may be an additional mechanism through which IL-33 contributes to inflammatory activation of the vessel wall.