A diagnosis of endometriosis is based upon the histological identification of endometrial tissue at ectopic sites which are commonly located on the pelvic organs, the peritoneum and ovary. In rare ...cases, ectopic lesions can be found in other organs, such as kidney, bladder, lung or brain. Diagnosis is achieved by laparoscopic intervention followed by histological confirmation of endometriotic tissue. Prevalence is estimated at approximately 10% in the general female population with many patients experiencing pain and/or infertility. Currently, the implantation hypothesis by Sampson is the most accepted hypothesis about the pathogenesis of endometriosis. However, the occurrence of endometriosis in patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome who sometimes lack a uterus or endometrium seems to suggest metaplasia as a cause of endometriosis. A critical reevaluation of the literature about MRKH does not reveal conclusive evidence of an association of uterus/endometrium agenesis and endometriosis. Most often only MRI diagnoses of uterus/endometrium agenesis and only very rarely conclusive histological evidence of the endometriotic lesions are presented. In contrast, whenever biopsies were performed endometriosis always appeared together with uterus/endometrium remnants. Taken together, we suggest that MRKH patients only develop endometriosis if a uterus/endometrium is present which underscores and not contradicts the implantation hypothesis of Sampson.
Epithelial–mesenchymal transition (EMT) is an important process of cell remodeling characterized by the gradual loss of the epithelial phenotype and progressive gain of a mesenchymal phenotype. EMT ...is not an all-or-nothing process, but instead a transition of epithelial to mesenchymal cells with intermediate cell states. Recently, EMT was described in endometriosis, and many EMT-specific pathways like Twist, Snail, Slug, Zinc finger E-box-binding homeobox 1/2 (ZEB1/2), E/N-cadherin, keratins, and claudins are involved. However, as pointed out in this review, a comparison of the eutopic endometrium of women with and without endometriosis yielded only subtle changes of these EMT markers. Furthermore, only very few alterations in cell–cell contacts could be found but without changes in the epithelial phenotype. This suggests only a partial EMT which is not a prerequisite for the detachment of endometrial cells and, thus, not critical for the first step(s) in the pathogenesis of endometriosis. In contrast, the majority of changes in the EMT-related marker expression were found in the ectopic endometrium, especially in the three endometriotic entities, ovarian, peritoneal, and deep infiltrating endometriosis (DIE), compared with the eutopic endometrium. In this review, we examine the most important EMT pathways described in endometriosis and propose that partial EMT might result from the interaction of endometrial implants with their surrounding microenvironment.
(1) Background: Post-reperfusion syndrome (PRS) and electrolyte shifts (ES) represent considerable challenges during liver transplantation (LT) being associated with significant morbidity. We aimed ...to investigate the impact of hypothermic oxygenated machine perfusion (HOPE) on PRS and ES in LT. (2) Methods: In this retrospective study, we compared intraoperative parameters of 100 LTs, with 50 HOPE preconditioned liver grafts and 50 grafts stored in static cold storage (SCS). During reperfusion phase, prospectively registered serum parameters and vasopressor administration were analyzed. (3) Results: Twelve percent of patients developed PRS in the HOPE cohort vs. 42% in the SCS group (p = 0.0013). Total vasopressor demand in the first hour after reperfusion was lower after HOPE pretreatment, with reduced usage of norepinephrine (−26%; p = 0.122) and significant reduction of epinephrine consumption (−52%; p = 0.018). Serum potassium concentration dropped by a mean of 14.1% in transplantations after HOPE, compared to a slight decrease of 1% (p < 0.001) after SCS. The overall incidence of early allograft dysfunction (EAD) was reduced by 44% in the HOPE group (p = 0.04). (4) Conclusions: Pre-transplant graft preconditioning with HOPE results in higher hemodynamic stability during reperfusion and lower incidence of PRS and EAD. HOPE has the potential to mitigate ES by preventing hyperpotassemic complications that need to be addressed in LT with HOPE-pre-treated grafts.
Claudins are the major components of tight junctions and are often deregulated in human cancer, permitting escape of cancer cells along with the acquisition of invasive properties. Similarly, ...endometrial cells also show invasive capabilities; however, the role of tight junctions in endometriosis has only rarely been examined. In this study, we analyzed the protein expression and localization of claudin-7 and claudin-11 in human eutopic and ectopic endometrium and endometrial cell lines. We identified claudin-7 primarily at the basolateral junctions of the glandular epithelial cells in eutopic endometrium as well as in the ectopic lesions in nearly all glands and cysts. Quantification of claudin-7 localization by HSCORE showed a slight increase in peritoneal and deep infiltrating endometriosis (DIE) compared to eutopic endometrium. In contrast, claudin-11 was localized mainly in the apicolateral junctions in nearly all glandular epithelial cells of the eutopic endometrium. Interestingly, we observed a deregulation of claudin-11 localization to a basal or basolateral localization in ovarian (
< .001), peritoneal (
< .01), and DIE (
< .05) and a moderately decreased abundance in ovarian endometriosis. In endometrial cell lines, claudin-7 was only present in epithelial Ishikawa cells, and silencing by small-interfering RNA increased cell invasiveness. In contrast, claudin-11 could be demonstrated in Ishikawa and endometriotic 12Z and 49Z cells. Silencing of claudin-11 decreased invasiveness of 12Z slightly but significantly in 49Z. We suggest that although claudin-7 and claudin-11 can be found in nearly all eutopic and ectopic epithelial cells, the impaired localization of claudin-11 in ectopic endometrium might contribute to the pathogenesis of endometriosis.
The new competency-based continuing education regulations for surgical training (WBO) came into effect in Bavaria in August 2022.
From May to July 2022, we conducted an anonymized online survey among ...Bavarian general and visceral surgeons and surgical residents (ÄiW). The aim was to survey expectations of the effects of the new WBO.
The response rate was 35%. In total data could be collected from 80 persons, 36 ÄiW (45%), 30 specialists and senior physicians (37.5%) and 14 chief physicians (17.5%). The majority of respondents worked at a university hospital (38.8%) or a regular provider (35%). A strengthening of the competence to act through implementation of the new WBO is seen by 41.3% and 55.7% see independent operating under partial supervision by the instructor as a goal. Of the respondents 50% see the required case numbers as not achievable and 55.1% deny reaching them in the expected period of 6 years. About 60% do not expect to be able to train the same number of ÄiWs in the same amount of time. Almost 75% of the respondents state that from their point of view, a good continuing education with the achievement of a solid competence to act would not work without overtime hours. About 44% of the respondents expect that a full surgical training would continue to be possible at their institution.
Both among the instructors and among the trainees there is a tendency to fear that realistic training, in particular the achievement of the guideline figures, will no longer be possible in the usual further training time. This necessitates the consistent implementation of structured continuing education with a high degree of transparency in training.
Purpose
Claudins as the major components of tight junctions are important in maintaining cell–cell integrity and thus function as a barrier. Dysregulation of the claudins is often associated with ...loss of the epithelial phenotype, a process called epithelial–mesenchymal transition (EMT), which most often results in gain of migrative and invasive properties. However, the role of claudins in the endometrium or endometriosis has only rarely been examined.
Methods
In this study, we investigated localization of claudin-2 and claudin-3 in the eutopic and ectopic endometrium with immunohistochemistry. A detailed quantification with HSCORE was performed for claudin-2 and claudin-3 in endometrium without endometriosis and in cases with endometriosis compared to the three endometriotic entities: peritoneal, ovarian, and deep-infiltrating endometriosis.
Results
We found a preferential localization of both claudins in the glandular and the luminal epithelial cells in the endometrium with and without endometriosis. Quantification of localization of both claudins showed no differences in eutopic endometrium of control cases compared to cases with endometriosis. Furthermore, both claudins are localized highly similar in the ectopic compared to the eutopic endometrium, which is in clear contrast to previously published data for claudin-3.
Conclusion
From our results, we conclude that localization of claudin-2 and claudin-3 is highly stable in eutopic and ectopic endometrium without any loss of the epithelial phenotype and thus do not contribute to the pathogenesis of endometriosis.
Are other pain symptoms in addition to dysmenorrhea, dyspareunia, dyschezia, dysuria, and chronic pelvic pain correlated to endometriosis and suitable for a clinical prediction model?
We conducted a ...prospective study from 2016 to 2022, including a total of 269 women with numerous pain symptoms and other parameters. All women filled out two questionnaires and were examined by palpation and transvaginal ultrasound (TVUS). In cases of suspected deep endometriosis, magnetic resonance imaging (MRI) was performed. After the operation, endometriosis was diagnosed by histological examination.
All in all, 30 significant parameters and 6 significant numeric rating scale (NRS) scores associated with endometriosis could be identified: 7 pain adjectives, 8 endometriosis-associated pain symptoms, 5 pain localizations, 6 parameters from the PainDETECT, consumption of analgesics, and allergies. Furthermore, longer pain duration (before, during, and after menstruation) was observed in women with endometriosis compared to women without endometriosis (34.0% vs. 12.3%, respectively). Although no specific pain for endometriosis could be identified for all women, a subgroup with endometriosis reported radiating pain to the thighs/legs in contrast to a lower number of women without endometriosis (33.9% vs. 15.2%, respectively). Furthermore, a subgroup of women with endometriosis suffered from dysuria compared to patients without endometriosis (32.2% vs. 4.3%, respectively). Remarkably, the numbers of significant parameters were significantly higher in women with endometriosis compared to women without endometriosis (14.10 ± 4.2 vs. 7.75 ± 5.8, respectively). A decision tree was developed, resulting in 0.904 sensitivity, 0.750 specificity, 0.874 positive predictive values (PPV), 0.802 negative predictive values (NPV), 28.235 odds ratio (OR), and 4.423 relative risks (RR). The PPV of 0.874 is comparable to the positive prediction of endometriosis by the clinicians of 0.86 (177/205).
The presented predictive model will enable a non-invasive diagnosis of endometriosis and can also be used by both patients and clinicians for surveillance of the disease before and after surgery. In cases of positivety, as evaluated by the questionnaire, patients can then seek advice again. Similarly, patients without an operation but with medical therapy can be monitored with the questionnaire.
Zusammenfassung
Einleitung
Die neue, vermehrt kompetenzbasierte Weiterbildungsordnung für die chirurgische Weiterbildung (WBO) trat in Bayern im August 2022 in Kraft.
Methoden
Von Mai bis Juli 2022 ...führten wir eine anonymisierte Onlineumfrage unter den bayerischen Allgemein- und Viszeralchirurginnen und -cChirurgen sowie den Ärzt*innen in Weiterbildung (ÄiW) durch. Ziel war die Erfragung der Erwartungen an die Effekte der neuen WBO.
Ergebnisse
Die Rücklaufquote betrug 35 %; insgesamt konnten Daten von 80 Personen erhoben werden: 36 ÄiW (45 %), 30 Fach- und Oberärzt*innen (37,5 %) und 14 Chefärzt*innen (17,5 %). Die Mehrheit der Befragten arbeitete an einem Universitätsklinikum (38,8 %) oder Regelversorger (35 %). Eine Stärkung der Handlungskompetenz durch Umsetzung der neuen WBO erwarten 41,3 % und 55,7 % sehen als Ziel ein „selbstständiges Operieren unter teilweiser Aufsicht durch den Ausbilder“. 50 % sehen die geforderten Richtzahlen als nicht erreichbar an, bzw. 55,1 % verneinen ein Erreichen derselben im Zeitraum von 6 Jahren. Etwa 60 % erwarten, nicht die gleiche Anzahl an ÄiW in der gleichen Zeit ausbilden zu können. Fast 75 % der Befragten geben an, dass aus ihrer Sicht eine gute Weiterbildung mit Erreichen einer soliden Handlungskompetenz ohne Überstunden nicht funktioniere. Etwa 44 % der Befragten erwarten, dass die volle Weiterbildung an ihrem Haus auch weiterhin möglich sei.
Schlussfolgerung
Sowohl unter den Weiterbilder*innen als auch unter den ÄiW besteht tendenziell die Sorge, dass eine realistische Weiterbildung – insbesondere das Erreichen der Richtzahlen in der bisher üblichen Weiterbildungszeit – nicht möglich sein wird. Notwendig ist daher die konsequente Umsetzung einer strukturierten Weiterbildung mit hoher Transparenz der Ausbildung.
Abstract
We present the first results from a 100-day Swift, NICER, and ground-based X-ray–UV–optical reverberation mapping campaign of the Narrow-line Seyfert 1 Mrk 335, when it was in an ...unprecedented low X-ray flux state. Despite dramatic suppression of the X-ray variability, we still observe UV–optical lags as expected from disk reverberation. Moreover, the UV–optical lags are consistent with archival observations when the X-ray luminosity was >10 times higher. Interestingly, both low- and high-flux states reveal UV–optical lags that are 6–11 times longer than expected from a thin disk. These long lags are often interpreted as due to contamination from the broad line region; however the
u-
band excess lag (containing the Balmer jump from the diffuse continuum) is less prevalent than in other active galactic nuclei. The Swift campaign showed a low X-ray-to-optical correlation (similar to previous campaigns), but NICER and ground-based monitoring continued for another 2 weeks, during which the optical rose to the highest level of the campaign, followed ∼10 days later by a sharp rise in X-rays. While the low X-ray countrate and relatively large systematic uncertainties in the NICER background make this measurement challenging, if the optical does lead X-rays in this flare, this indicates a departure from the zeroth-order reprocessing picture. If the optical flare is due to an increase in mass accretion rate, this occurs on much shorter than the viscous timescale. Alternatively, the optical could be responding to an intrinsic rise in X-rays that is initially hidden from our line of sight.
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