Rolle neurotroper und muskulotroper Spasmolytika in der In- vitro Fertilisation (IVF): Untersuchungen am perfundierten Schweineuterus

Background and aim: The aim of this thesis is to avoid iatrogenic induced uterine contractions and the inhibition of the basal activity of the uterus, which differs individually, during the procedure of embryo transfer in IVF. The embryo transfer is one of the key- factors for successful embryo implantation and for the improvement of the resulting rate of pregnancy. The aim of this study was to investigate the effect of different neurotropic and musculotropic spasmolytic agents (Buscopan®, Belladonnysat®, Spasmalgan®, Paverysat®, Dolantin®, Paveriwern®, Novaminsulfon®) on the spontaneous as well as Oxytocin- induced contractions in perfused isolated swine uteri. Methods: Altogether approximately 80 swine uteri were prepared for these experiments in an established perfusion system. The perfusion model used provides physiological conditions for at least 8 hours and makes it possible to simulate various influences on the uterine function. After initiation of spontaneous uterine contractions increasing dosages of the spasmolytic agents were applied with a bolus injection and the changes in uterine pressure were recorded with an intrauterine placed tip- catheter. Afterwards this was followed by a computer- based graphical and statistical evaluation. Results and observations: Particularly with the musculotropic acting relaxants Spasmalgan® (Denaverin) it was possible to achieve significant results for all dosages and parameters investigated. Considering the physiology of muscles one can recognize an advantage of the musculotropic agents compared to neurotropic spasmolytics with reference to the inhibition of contractions. Also the experiments with Dolantin® showed promising results. For Paverysat® there was an initial increase of contractions observed that allows interesting connections to a possible support of the rapid directed sperm transport. Conclusion: Considering the latest studies, the physiology of the female menstrual cycle and the standard technique of embryo transfer, it seems that at present a combination of different drugs with a positive ability to reduce uterine contractions provides the best conditions to prepare the uterus sufficiently for embryo implantation. Especially Spasmalgan® and Dolantin® could play an important role in improving the pregnancy- rate after IVF in the future.Hintergrund und Ziele: Die Vermeidung iatrogen induzierter uteriner Kontraktionen und Hemmung der individuell unterschiedlich stark ausgeprägten Grundaktivität der Gebärmutter während der Prozedur des Embryotransfers in der IVF sind heute unter anderem bekannte Schlüsselfaktoren für den Erfolg der Keimimplantation bzw. die Verbesserung der Schwangerschaftsrate. Ziel dieser Studie war es nun den Effekt verschiedener neuro- und muskulotroper spasmolytischer Medikamente (Buscopan®, Belladonnysat®, Spasmalgan®, Paverysat®, Dolantin®, Paveriwern®, Novaminsulfon®) auf spontane bzw. Oxytocin- induzierte Kontraktionen am isolierten perfundierten Schweineuterus zu untersuchen. Methoden: Insgesamt wurden etwa 80 Schweineuteri in etablierter Art und Weise für die Versuchsreihe präpariert. Mit dem verwendeten Perfusionsmodell ist es über einen Zeitraum von bis zu 8 Stunden möglich verschiedenste Einflüsse auf die Uterusfunktionen unter physiologischen Bedingungen zu simulieren. Nach Initiierung spontaner Uteruskontraktionen wurden die Medikamente in aufsteigender Dosierung im Bolus appliziert und die Druckänderung mit Hilfe eines intrauterin platzierten Messsensors digital aufgezeichnet. Anschließend erfolgte eine Computer- gestützte grafische sowie statistische Auswertung der erhobenen Daten. Ergebnisse und Beobachtungen: Vor allem für das muskulotrop relaxierend wirkende Spasmalgan® (Denaverin) konnten für jede Dosierung und alle ermittelten Parameter signifikante Ergebnisse erzielt werden. Unter Berücksichtigung der Muskelphysiologie lässt sich an Hand dieses Experimentes ein Vorteil der muskulotropen, gegenüber den neurotropen Spasmolytika bezüglich der Kontraktionshemmung erkennen. Auch die Versuche mit Dolantin® lieferten Erfolg versprechende Resultate. Für Paverysat® konnte initial eine Kontraktionszunahme beobachtet werden, was wiederum interessante Querverbindungen einer möglichen Unterstützung des schnellen gerichteten Samentransports zulässt. Klinische Schlussfolgerung: Unter Berücksichtigung der aktuellen Studienlage, der Physiologie des weiblichen Menstruationszyklus und der standardisierten Technik des Embryotransfers scheint im Moment eine Kombination verschiedener Medikamente mit positivem Einfluss auf die Reduktion der Uterusaktivität die besten Voraussetzungen zu bieten, um die Gebärmutter optimal auf die Keimimplantation vorzubereiten. Hierbei könnten auch auf Grund dieser Studie insbesondere Spasmalgan® und Dolantin® eine entscheidende Rolle zur Verbesserung der Schwangerschaftsrate nach IVF spielen

The Use of Contrast-Enhanced Sonography for Therapy Monitoring of Metastatic Lymph Nodes: A Systematic Review

Metastatic cervical lymph nodes are a frequent finding in head and neck squamous cell carcinoma (HNSCC). If a non-surgical approach is primarily chosen, a therapy response evaluation of the primary tumor and the affected lymph nodes is necessary in the follow-up. Supplementary contrast-enhanced ultrasound (CEUS) can be used to precisely visualize the microcirculation of the target lesion in the neck, whereby malignant and benign findings differ in their uptake behavior. The same applies to many other solid tumors. For various tumor entities, it has already been shown that therapy monitoring is possible through regular contrast-enhanced sonography of the primary tumor or the affected lymph nodes. Thus, in some cases, maybe in the future, a change in therapy strategy can be achieved at an early stage in the case of non-response or, in the case of therapy success, a de-escalation of subsequent (surgical) measures can be achieved. In this paper, a systematic review of the available studies and a discussion of the potential of therapy monitoring by means of CEUS in HNSCC are presented

Exhaustion and cardiovascular risk factors: the role of vagally-mediated heart rate variability

Purpose Exhaustion symptoms are known to be associated with cardiovascular disease (CVD) risk; however, the underlying mechanisms remain unclear. Autonomic imbalance, as indicated by reductions in vagally-mediated heart rate variability (vmHRV), appears to be a valid candidate for such a biological link, as it has been associated with both exhaustion symptoms and CVD risk and mortality. Methods The present study examined a potential mediation of vmHRV on the association between exhaustion symptoms and self-reported CVD risk factors as well as the age dependency of this mediation in a large, heterogeneous sample of the Dresden Burnout Study (N = 388; 72.9% females; Mage = 42.61, SD = 11.67). Results Results indicate that exhaustion symptoms were indirectly associated with CVD risk factors through vmHRV even after adjusting for well-known confounders (i.e., sex, body mass index, depressive symptoms). Moreover, this pattern was significant only among middle-aged (i.e., 54.27 years) and older individuals. Conclusions Our findings add to growing evidence that autonomic imbalance may be a key biological link between exhaustion symptoms and CVD risk in middle-aged and older individuals. Implications for public health are discussed

Primary Surgical Therapy for Locally Limited Oral Tongue Cancer

Objectives. The aim of this study was to assess the efficacy of primary surgical treatment in the management of locally limited oral tongue carcinoma. Methods. A retrospective evaluation was carried out for all patients treated with primary surgery for pT1-pT2 oral tongue carcinomas at a tertiary referral center between 1980 and 2005. All cases were assessed for disease-specific survival and local control rates in relation to T classification, N classification, infiltration depth of the primary tumor, and decision making on neck management and adjuvant therapy. The cases were additionally evaluated for the incidence of major complications and tracheotomies. Results. 263 cases were assessed. The 5-year disease-specific survival rate was 75.2%. Positive neck disease was shown to be a significant negative prognostic factor. The occult metastasis rate was 20.2%. Conclusions. Primary surgical treatment is a very effective modality against T1-T2 oral tongue carcinoma, and a low rate of complications can be anticipated

Prehabilitation of dysphagia in the therapy of head and neck cancer- a systematic review of the literature and evidence evaluation

BackgroundPrehabilitation is becoming increasingly important in oncology because of the significant survival benefits that the reduction of malnutrition provide. Specifically, tumor- and therapy-related dysphagia leads to malnutrition in more than half of head and neck tumor patients. Studies describe the positive effects of an early onset of swallow-specific prehabilitation on the protection of the swallowing function. This paper intents to evaluate the existing evidence on the efficacy of preventive forms of swallowing therapy.MethodsA systematic literature search was performed in February 2022 in the Cochrane Library, MEDLINE via PubMed, and ClinicalTrials.gov databases for randomized controlled trials investigating preventive swallowing therapy in head and neck tumor patients. This Procedure complies with the PRISMA statement. The RCTs were evaluated by using the PEDro Scale and the Cochrane Risk of Bias tool RoB2.ResultsFive randomized-controlled trials with 423 participants were identified. Four Studies showed moderate to high quality in the PEDro analysis, one showed less. The risk of bias was high in all studies because there was no possibility for blinding and there were high dropout rates. Heterogeneity in interventions, measurement instruments, measurement time points, and outcomes limits a general statement about which swallowing exercises are suitable for the prevention of dysphagia in head and neck tumor patients. Evidence is provided for short-term effects (≤24 months) on functional aspects of swallowing and quality of life. Overall, a decreasing adherence over time was observed in the intervention groups.DiscussionInitial studies describe swallowing-specific prehabilitation programs in head and neck tumor patients as effective, at least in the short term, whereas long-term effects need to be further investigated. At the current time the evidence base for clear recommendations does not appear to be sufficiently high and studies share a high risk of bias. Further well-designed research, especially considering the conditions in the national health care system, is needed.OtherThere was no funding and no registration

The perfused swine uterus model: long-term perfusion

Background It has previously been shown that the viability of swine uteri can be maintained within the physiological range in an open perfusion model for up to 8 hours. The aim of this study was to assess medium- to long-term perfusion of swine uteri using a modified Krebs–Ringer bicarbonate buffer solution (KRBB) in the established open perfusion model. Methods In an experimental study at an infertility institute, 30 swine uteri were perfused: group 1: n = 11, KRBB; group 2: n = 8, modified KRBB with drainage of perfusate supernatant; group 3: n = 11, modified KRBB with drainage of perfusate every 2 h and substitution with fresh medium. Modified and conventional KRBB were compared with regard to survival and contraction parameters: intrauterine pressure (IUP), area under the curve (AUC), and frequency of contractions (F). Results Modified KRBB showed significantly higher IUP, AUC, and F values than perfusion with conventional KRBB. In group 3, the organ survival time of up to 17 h, with a 98% rate of effective contraction time, differed significantly from group 1 (P < 0.001). Conclusions Using modified KRBB in combination with perfusate substitution improves the open model for perfusion of swine uteri with regard to survival time and quality of contraction parameters. This model can be used for medium- to long-term perfusion of swine uteri, allowing further metabolic ex vivo studies in a cost-effective way and with little logistic effort

Multiparametric Sonographic Imaging of Thyroid Lesions: Chances of B-Mode, Elastography and CEUS in Relation to Preoperative Histopathology

Background: The aim was to improve preoperative diagnostics of solid non-cystic thyroid lesions by using new high-performance multiparametric ultrasound examination techniques. Methods: Multiparametric ultrasound consists of B-mode, shear-wave elastography and contrast enhanced ultrasound (CEUS) including Time-Intensity-Curve (TIC) analysis. A bolus of 1–2.4 mL Sulfur Hexafluorid microbubbles was injected for CEUS. Postoperative histopathology was the diagnostic gold standard. Results: 116 patients were included in this study. 102 benign thyroid nodules were diagnosed as well as 20 carcinomas. Suspicious B-mode findings like microcalcifications, a blurry edge and no homogeneous sonomorphological structure were detected in 60, 75 and 80% of all carcinomas but only in 13.7, 36.3 and 46.1% of all benign lesions. The average shear-wave elastography measurements of malignant lesions (4.6 m/s or 69.8 kPa centrally and 4.2 m/s or 60.1 kPa marginally) exceed the values of benign nodules. Suspicious CEUS findings like a not-homogeneous wash-in and a wash-out were detected almost twice as often in carcinomas. Conclusion: Multiparametric ultrasound offers new possibilities for the preoperative distinction between benign and malignant thyroid nodules. A score based system of B-mode, shear-wave and CEUS malignancy criteria shows promising results in the detection of thyroid carcinomas. It reaches a sensitivity of 95% and specificity of 75.49%

Expressional analysis of disease-relevant signalling-pathways in primary tumours and metastasis of head and neck cancers

Head and neck squamous cell carcinoma (HNSCC) often metastasize to lymph nodes resulting in poor prognosis for patients. Unfortunately, the underlying molecular mechanisms contributing to tumour aggressiveness, recurrences, and metastasis are still not fully understood. However, such knowledge is key to identify biomarkers and drug targets to improve prognosis and treatments. Consequently, we performed genome-wide expression profiling of 15 primary HNSSCs compared to corresponding lymph node metastases and non-malignant tissue of the same patient. Differentially expressed genes were bioinformatically exploited applying stringent filter criteria, allowing the discrimination between normal mucosa, primary tumours, and metastases. Signalling networks involved in invasion contain remodelling of the extracellular matrix, hypoxia-induced transcriptional modulation, and the recruitment of cancer associated fibroblasts, ultimately converging into a broad activation of PI3K/AKT-signalling pathway in lymph node metastasis. Notably, when we compared the diagnostic and prognostic value of sequencing data with our expression analysis significant differences were uncovered concerning the expression of the receptor tyrosine kinases EGFR and ERBB2, as well as other oncogenic regulators. Particularly, upregulated receptor tyrosine kinase combinations for individual patients varied, implying potential compensatory and resistance mechanisms against specific targeted therapies. Collectively, we here provide unique transcriptional profiles for disease predictions and comprehensively analyse involved signalling pathways in advanced HNSCC

Early Stage Oropharyngeal Carcinomas: Comparing Quality of Life for Different Treatment Modalities

Objective. To compare long-term quality of life outcomes after treating early stage oropharyngeal carcinoma either with surgery, surgery combined with radiotherapy, or surgery combined with chemoradiotherapy. Methods. Questionnaire based method: 111 eligible patients agreed to fill out a quality of life questionnaire. Results. Of the 32 scales contained in the EORTC's combined QLQ-C30 and HN35, 11 scales show significantly better results for the surgery-only treatment group when compared to either surgery combined with radiotherapy or surgery combined with any type of adjuvant therapy. These eleven scales are role function (P = 0.019/0.008), social function (P = 0.01/0.034), nausea (P = 0.017/0.025), pain (P = 0.014/0.023), financial problems (P = 0.030/0.012), speech (P = 0.02/0.015), social eating (P = 0.003/<0.001), mouth opening (P = 0.033/0.016), sticky saliva (P = 0.001/<0.001), swallowing (P < 0.001/<0.001), and dry mouth (P < 0.001/0.001). Conclusion. Treatment of early stage oropharyngeal carcinoma with surgery alone has definite advantages over treatments including any form of adjuvant therapy when considering quality of life. Advantages manifest themselves especially in functional aspects of the head and neck realm; however general health aspects as well as psychosocial aspects show improvements as well. This study does not show any indication of QOL-related drawbacks of surgery-only treatment approaches