Different Forms of TFF3 in the Human Endocervix, including a Complex with IgG Fc Binding Protein (FCGBP), and Further Aspects of the Cervico-Vaginal Innate Immune Barrier.

TFF3 is a typical secretory poplypeptide of mucous epithelia belonging to the trefoil factor family (TFF) of lectins. In the intestine, respiratory tract, and saliva, TFF3 mainly exists as a high-molecular-mass complex with IgG Fc binding protein (FCGBP), which is indicative of a role in mucosal innate immunity. For the first time, we identified different forms of TFF3 in the endocervix, i.e., monomeric and homodimeric TFF3, as well as a high-molecular-mass TFF3-FCGBP complex; the latter also exists in a hardly soluble form. Immunohistochemistry co-localized TFF3 and FCGBP. Expression analyses of endocervical and post-menopausal vaginal specimens revealed a lack of mucin and TFF3 transcripts in the vaginal specimens. In contrast, genes encoding other typical components of the innate immune defense were expressed in both the endocervix and vagina. Of note, FCGBP is possibly fucosylated. Endocervical specimens from transgender individuals after hormonal therapy showed diminished expression, particularly of FCGBP. Furthermore, mucus swabs from the endocervix and vagina were analyzed concerning TFF3, FCGBP, and lysozyme. It was the aim of this study to illuminate several aspects of the cervico-vaginal innate immune barrier, which is clinically relevant as bacterial and viral infections are also linked to infertility, pre-term birth and cervical cancer.

Protective effect of pre-operative conization in patients undergoing surgical treatment for early-stage cervical cancer.

OBJECTIVE: The aim of this study was to investigate the impact of pre-operative conization on disease-free survival (DFS) in early-stage cervical cancer. METHODS: In this population-based cohort study we analysed from clinical cancer registries to determine DFS of women with International Federation of Gynecology and Obstetrics (FIGO) stage IA1-IB1 cervical cancer with respect to conization preceding radical hysterectomy performed between January 2010 and December 2015. RESULTS: Out of 993 datasets available for the analysis, 235 patients met the inclusion criteria of the current study. The median follow-up was 5.4 years. During the study period, 28 (11.9%) recurrences were observed. All of these occurred in patients with FIGO stage IB1. For further evaluation, patients with FIGO IB1 tumors <2 cm were further analysed and divided into two groups, based on pre-operative conization. Pre-operative conization was associated with a reduced rate of recurrence (p = 0.007), with only three (5.2%) recurrences in this group (CO) compared to 25 recurrences (21.0%) in the group without conization (NCO) preceding radical hysterectomy. DFS was estimated at 79.0% and 94.8% in NCO and CO, respectively (p = 0.008). After adjustment for other prognostic covariates, conization remained a favourable prognostic factor for DFS (HR 0.27; 95% CI 0.08-0.93, p = 0.037). Lymph node involvement was the only unfavourable factor (HR 4.38; 95% CI 1.36-14.14, p = 0.014) in the multivariable analysis. CONCLUSIONS: Pre-operative conization is associated with improved DFS in early-stage cervical cancer independently of the surgical approach.

The effect of warm and humidified gas insufflation in gynecological laparoscopy on maintenance of body temperature: a prospective randomized controlled multi-arm trial.

BACKGROUND: Hypothermia is defined as a decrease in body core temperature to below 36 °C. If intraoperative heat-preserving measures are omitted, a patient's temperature will fall by 1 - 2 °C. Even mild forms of intraoperative hypothermia can lead to a marked increase in morbidity and mortality. Using warm and humidified gas insufflation in laparoscopy may help in the maintenance of intraoperative body temperature. METHODS: In this prospective randomized controlled study, we investigated effects of temperature and humidity of the insufflation gas on intra- and postoperative temperature management. 150 patients undergoing gynecologic laparoscopic surgery were randomly assigned to either insufflation with non-warmed, non-humidified CO2 with forced air warming blanket (AIR), humidified warm gas without forced air warming blanket (HUMI) or humidified warm gas combined with forced air warming blanket (HUMI+). We hypothesized that the use of warmed laparoscopic gas would have benefits in the maintenance of body temperature and reduce the occurrence of hypothermia. RESULTS: The use of warm and humidified gas insufflation alone led to more hypothermia episodes with longer duration and longer recovery times as well as significantly lower core body temperature compared to the other two groups. In the comparison of the AIR group and HUMI + group, HUMI + patients had a significantly higher body temperature at arrival at the PACU (Post Anaesthesia Care Unit), had the least occurrence of hypothermia and suffered from less shivering. CONCLUSION: The use of warm and humidified gas insufflation alone does not sufficiently warm the patients. The optimal temperature management is achieved in the combination of external forced air warming and insufflation of warm and humidified laparoscopy gas.

Warm and humidified insufflation gas during gynecologic laparoscopic surgery reduces postoperative pain in predisposed patients-a randomized, controlled multi-arm trial.

BACKGROUND: Postoperative pain remains a common problem in gynecologic laparoscopy, especially in head zone-related regions, triggered by intra-abdominal pressure during capnoperitoneum. Humidified and prewarmed insufflation gas may ameliorate pain and be beneficial. METHODS: This prospective randomized controlled parallel group multi-arm single-center study investigated the effects of temperature and humidity of insufflation gas on postoperative pain during gynecologic laparoscopy with a duration ≥ 60 min. Female participants (18-70 years) were blinded and randomly assigned-computer generated-to either insufflation with dry cold CO2 with forced air warming blanket ("AIR"), humidified warm gas without forced air warming blanket ("HUMI"), or humidified warm gas with forced air warming blanket ("HUMI +"). We hypothesized that using humidified warm gas resulted in lower pain scores and less analgesic consumption. The primary endpoint postoperative pain was assessed for different pain localizations every 12 h during 7 days after surgery. Secondary endpoints were demand for painkillers and epidural anesthetics, length of stay in recovery room, and hospital stay. (Registration: ClinicalTrials.gov NCT02781194-completed). RESULTS: 150 participants were randomized. Compared to group "AIR" (n = 48), there was significantly less pain in group "HUMI +" (n = 48) in the recovery room (- 1.068; 95% CI - 2.08 to - 0.061), as well as significantly less ibuprofen use at day two (- 0.5871 g ± 0.258; p-value = 0.0471). Other variables did not change significantly. Stratification for presence of endometriosis or non-previous abdominal surgery in patient history revealed significantly less pain in both groups "HUMI" (n = 50) and "HUMI +" versus group "AIR." Related side effects were not noted. CONCLUSION: In the overall population, the use of warm, humidified insufflation gas did not yield clinically relevant effects; however, in predisposed patients with endometriosis and who could otherwise expect high pain levels, warm and humidified gas may be beneficial.

Mechanisms of estrogen-induced venous thromboembolism.

The use of oral contraceptives (OC) is a well established risk factor for venous thrombosis. It has been known for many years that almost all haemostatic parameters i.e. plasma levels of coagulation factors, anticoagulant proteins and proteins involved in the fibrinolytic pathway change during OC use. The discovery of several risk factors of venous thrombosis in the 1990s shed new light on the association between the effects of OC on the haemostatic system and the increased risk of venous thrombosis. In this review, we summarize the current knowledge on the effects of different kinds of hormonal contraceptives (OC, transdermal contraceptives, vaginal ring and levonorgestrel-releasing intrauterine device) on haemostatic variables and the relationship between the changes of these variables and the risk of venous thrombosis.