The cytokines IL-1b and IL-18 are upregulated in the placenta of recurrent miscarriage patients [Poster abstract]

Problem Recurrent miscarriage (RM) remains a relevant clinical problem as in about 50% of the affected women a cause cannot be identified. An exaggerated maternal immune response at the feto-maternal interphase is considered as one important mechanism for unexplained RM. Cytokines seem to play a crucial role to prevent rejection of the semi-allogenous fetus by the maternal immune system. Therefore, this study investigates cytokine secretion profiles in early pregnancy loss. Method of Study Women with an inconspicuous family and medical history were included in the present study. The TaqMan® Human Cytokine Network Array was applied in order to investigate differences in cytokine mRNA expression in placental tissue of patients with healthy pregnancies (n = 15) and RM (n = 15). The protein expression of IL- 1β and IL-18 was examined by immunohistochemical staining in the decidua of healthy pregnancies (n = 15), spontaneous miscarriage (SM) (n = 18) and RM (n = 15). Double- immunofluorescence was carried out for the characterization of IL- 1β and IL-18 expressing cells in the decidua. Results Gene expression analysis revealed an overexpression of IL- 1β and IL-18 in RMpatients. IL-18 protein expression was significantly upregulated in the decidua of the RMgroup (p = 0.031). In SM specimens there was no significant difference in IL-18 expression when compared to healthy controls (p=0.172). Immunohistochemical staining showed a significant elevated expression of IL-1β in the decidua of RM (p = 0.01) and SM patients (p = 0.001) in comparison to the control group. Double-immunofluorescence identified decidual stroma cells as IL- 1β and IL-18 expressing cells. Conclusion IL- 1β expression is significantly elevated in the decidua in both miscarriage groups and IL-18 upregulation is restricted to RM patients. The overexpression of IL- 1β and IL-18 might lead to or may be a result of a pro-inflammatory immune response at the fetomaternal interphase and could consequently induce miscarriage. The secretion of both cytokines is stimulated by the activated inflammasome NLRP3 (NOD-, LRR- and pyrin domain containing 3) and the inhibition of this upstream might be a new therapeutic approach for miscarriage patients

Nectin‐2 in ovarian cancer: how is it expressed and what might be its functional role?

Nectin‐2 is an adhesion molecule that has been reported to play a role in tumor growth, metastasis and tumor angiogenesis. Herein, we investigated Nectin‐2 in ovarian cancer patients and in cell culture. Tumor as well as peritoneal biopsies of 60 ovarian cancer patients and 22 controls were dual stained for Nectin‐2 and CD31 using immunohistochemistry. Gene expression of Nectin‐2 was quantified by real‐time PCR and differences analyzed in relation to various tumor characteristics. In the serum of patients, vascular endothelial growth factor (VEGF) was quantified by ELISA. Effect of VEGF on Nectin‐2 expression as well as permeability was investigated in HUVEC. In tumor biopsies, Nectin‐2 protein was mainly localized in tumor cells, whereas in peritoneal biopsies, clear colocalization was found in the vasculature. T3 patients had a significantly higher percentage of positive lymph nodes and this correlated with survival. Nectin‐2 was significantly upregulated in tumor biopsies in patients with lymph node metastasis and with residual tumor >1 cm after surgery. Nectin‐2 expression was significantly suppressed in the peritoneal endothelium of patients associated with significantly increased VEGF serum levels. In cell culture, VEGF stimulation led to a significant downregulation of Nectin‐2 which was reversed by VEGF‐inhibition. In addition, Nectin‐2 knockdown in endothelial cells was associated with significantly increased endothelial permeability. Nectin‐2 expression in ovarian cancer may support tumor cell adhesion, leading to growth and lymph node metastasis. In addition, VEGF‐induced Nectin‐2 suppression in peritoneal endothelium may support an increase in vascular permeability leading to ascites production

Evaluating a novel 3D printed model for simulating Large Loop Excision of the Transformation Zone (LLETZ)

Background Electrosurgical excisions are common procedures for treating cervical dysplasia and are often seen as minor surgeries. Yet, thorough training of this intervention is required, as there are considerable consequences of inadequate resections, e.g. preterm birth, the risk of recurrence, injuries and many more. Unfortunately, there is a lack of sufficiently validated possibilities of simulating electrosurgeries, which focus on high fidelity and patient safety. Methods A novel 3D printed simulator for examination and electrosurgical treatment of dysplastic areas of the cervix was compared with a conventional simulator. Sixty medical students experienced a seminar about cervical dysplasia. Group A underwent the seminar with the conventional and Group B with the novel simulator. After a theoretical introduction, the students were randomly assigned by picking a ticket from a box and went on to perform the hands-on training with their respective simulator. Each student first obtained colposcopic examination training. Then he or she performed five electrosurgical excisions (each). This was assessed with a validated score, to visualize their learning curve. Furthermore, adequate and inadequate resections and contacts between electrosurgical loop and vagina or speculum were counted. Both groups also assessed the seminar and their simulator with 18 questions (Likert-scales, 1–10, 1 = strongly agree / very good, 10 = strongly disagree / very bad). Group B additionally assessed the novel simulator with four questions (similar Likert-scales, 1–10). Results Nine of 18 questions showed statistically significant differences favoring Group B (p < 0.05). Group B also achieved more adequate R0-resections and less contacts between electrosurgical loop and vagina or speculum. The learning curves of the performed resections favored the novel simulator of Group B without statistically significant differences. The four questions focusing on certain aspects of the novel simulator indicate high appreciation of the students with a mean score of 1.6 points. Conclusion The presented novel simulator shows several advantages compared to the existing model. Thus, novice gynecologists can be supported with a higher quality of simulation to improve their training and thereby patient safety

Optimized process quality in certified breast centers through adherence to stringent diagnostic and therapeutic algorithms effects of structural as well as socio-demographic factors on start of therapy

Purpose An increasing incidence of breast cancer can be observed worldwide. Since a delay of therapy can have a negative impact on prognosis, timely cancer care is an important quality indicator. By receiving treatment at a certified breast cancer center, the patient has the best chance of treatment in accordance with guidelines and the best prognosis. The identification of risk factors for a delay of therapy is of central importance and should be the basis for a continuous optimization of treatment at breast cancer centers. Methods This retrospective study included women with breast cancer (primary diagnosis, relapse, or secondary malignancy) at the University Hospital Würzburg in 2019 and 2020. Data were retrieved from patients’ records. Correlations and regression analyses were performed to detect potential risk factors for treatment delay. Results Patients who received the histological confirmation of breast cancer at an external institution experienced a later therapy start than those patients who received the histological confirmation at the University Hospital Würzburg itself. (35.7 vs. 32.2 days). The interval between histological confirmation and the first consultation at the University Hospital Würzburg correlated statistically significant with age, distress and distance to the hospital. Conclusion Patients with an in-house diagnosis of breast cancer are treated more quickly than those whose diagnosis was confirmed in an external institution. We identified factors such as increased age, greater distance to the hospital as well as increased distress to prolong the time until start of oncological treatment. Intensified patient care should be offered to these subgroups