Female cancer survivors: sexual function, psychological distress, and remaining fertility.

PURPOSE: Improved survivorship in cancer patients leads to new challenging issues including potential impairment of quality of life, sexual function, and fertility. The aim of this study was to assess sexual dysfunction (SD) and psychological distress in female cancer survivors who underwent fertility preservation in the past in comparison to reviewed healthy control data from other published studies. Additionally, our focus was on the difference in SD between women with current desire to get pregnant and already completed family planning. METHODS: In this prospective study, 53 female cancer survivors who underwent fertility preservation at time of cancer diagnosis between 2010 and 2020 were invited to a gynecological exam, laboratory assessment, and two questionnaires (Female Sexual Function Index (FSFI) and Hospital anxiety and depression scale (HADS)) in 2022. These scores were compared to results in the literature of healthy controls and depending on anti-Mullerian-hormone (AMH) levels, current desire to have a child, and age. RESULTS: After a mean follow-up time of 70 ± 50 months, SD was detected in 60.4% (n = 32) of the 53 included patients. Normal results regarding HADS-D/anxiety and HADS-D/depression were found in 88.7% and 94.3% of patients, respectively. At time of follow-up, 69.9% (n = 40) regained regular menstrual cycles, 52.6% (n = 20) < 40 years showed a diminished ovarian reserve with AMH levels < 1.1 ng/ml and 28.3% (n = 15) suffered from infertility. CONCLUSION: Female cancer survivors may be at risk for SD. Cancer patients should be informed about possible sexual dysfunction already at the start of cancer treatment and during follow-up. In addition, contraception needs to be addressed if regular cycles occur as more than two-thirds of the women regained regular menstrual cycles.

Endometriosis and mental health disorders: identification and treatment as part of a multimodal approach.

Endometriosis is a disease marked by more than just pain and infertility, as it transcends the well-characterized physical symptoms to be frequently associated with mental health issues. This review focuses on the associations between endometriosis and anxiety, depression, sexual dysfunction, and eating disorders, all of which show a higher prevalence in women with the disease. Studies show that pain, especially the chronic pelvic pain of endometriosis, likely serves as a mediating factor. Recent studies evaluating genetic predispositions for endometriosis and mental health disorders suggest a shared genetic predisposition. Healthcare providers who treat women with endometriosis should be aware of these associations to best treat their patients. A holistic approach to care by gynecologists as well as mental health professionals should emphasize prompt diagnosis, targeted medical interventions, and psychological support, while also recognizing the role of supportive relationships in improving the patient's quality of life.

Let's Talk About Sex: Tyrolean Online Study on Reproductive Health Issues.

Introduction: The way pupils and university students talk about sex does not reflect their real understanding of reproductive health issues. Therefore, we developed a survey for pupils and students in Tyrol, Austria, to evaluate the current state of knowledge. Methods: Two questionnaires with 39 items for pupils (n = 369) and 53 items for university students (n = 537) were developed, and an online survey was carried out in Tyrol, Austria, between April and July 2022. A sum score for each correct answer to ten identical items in both questionnaires was used to compare groups (range: 0-11 points), with analysis performed using independent sample t-test, analyses of variance (ANOVAs) and chi-square test. Results: With regards to reproductive health issues and fertility awareness, female vs. male participants (p < 0.001), university students vs. pupils (p < 0.001) and medical students vs. other students (p < 0.001) had greater knowledge. Participants who had already had sexual intercourse showed a broader knowledge of contraception and fertility (p < 0.001).The age at which the decline of female fertility becomes relevant was misstated by the adolescents, who gave a mean age of 42.6 years compared to university students who asserted a mean age of 35.9 years (p < 0.001). Overall, the lowest rate of correct answers was found with respect to emergency contraception (30.7%), while knowledge of contraceptive methods was comparatively high (99.2%). Conclusion: Substantial lack of knowledge of reproductive health issues exists, with differences found between pupils and university students, between genders, and according to field of study. Future health and fertility awareness programs at school and university should focus on gender-specific aspects to prevent unplanned pregnancies, sexually transmitted diseases, and childlessness.

NK and T Cell Subtypes in the Endometrium of Patients with Recurrent Pregnancy Loss and Recurrent Implantation Failure: Implications for Pregnancy Success.

BACKGROUND: RPL and RIF are challenges in reproductive medicine. The immune system plays a pivotal role in endometrial receptivity, successful implantation, and pregnancy complications. Immunological changes have been associated with RPL and RIF. Understanding immune dysregulation especially in NK and T cell subtypes may lead to better diagnostic concepts and treatments. From July 2019 to August 2020 patients with RPL and RIF underwent a standardized diagnostic procedure including endometrial biopsies. Immune cell analysis was performed using flow cytometry. Patients were contacted in March 2023 and interviewed concerning their pregnancy outcomes following diagnostics. RESULTS: Out of 68 patients undergoing endometrial biopsies, 49 patients were finally included. Live birth rates were high with 72% in RPL and 86% in RIF. Immune cell analysis revealed that patients with RPL had more cytotoxic CD56dimCD16high cells, while RIF patients had more CD56+ uNK cells. RPL patients with pregnancy complications showed increased NKT cell percentages. CONCLUSION: Our findings suggest specific immune changes in RPL and RIF patients, offering potential therapeutic targets. Tailored immunotherapy based on endometrial immunophenotyping might be an option, but further research is needed.

Fertility, Contraception, and Fertility Preservation in Trans Individuals.

BACKGROUND: An increasing number of persons around the world are receiving the diagnosis of gender incongruence, and most of them are in their reproductive years. Safe contraception and fertility preservation are important issues for counseling. METHODS: This review is based on pertinent publications retrieved by a systematic search in the PubMed and Web of Science databases, employing the search terms "fertility," "contraception," "transgender," "gender-affirming hormone therapy" (GAHT), "ovarian reserve," and "testicular tissue." 908 studies were included, 26 of which entered the final analysis. RESULTS: Most of the available studies on fertility in trans persons undergoing GAHT reveal a marked effect on spermatogenesis, but no impairment of ovarian reserve. No studies are available on trans women; the data show that 59-87% of trans men use contraceptives, often mainly in order to suppress menstrual bleeding. Fertility preservation measures are mainly used by trans women. CONCLUSION: GAHT mainly impairs spermatogenesis; thus, counseling on fertility preservation should always be given before GAHT. More than 80% of trans men use contraceptives, mainly for their other effects such as suppression of menstrual bleeding. GAHT is not in itself a reliable method of contraception, and persons about to undergo GAHT should always receive contraceptive counseling.

Defining Models to Classify between Benign and Malignant Adnexal Masses Using Routine Laboratory Parameters.

Discrimination between benign and malignant adnexal masses is essential for optimal treatment planning, but still remains challenging in a routine clinical setting. In this retrospective study, we aimed to compare albumin as a single parameter to calculate models by analyzing laboratory parameters of 1552 patients with an adnexal mass (epithelial ovarian cancer (EOC): n= 294; borderline tumor of the ovary (BTO): n = 66; benign adnexal mass: n = 1192) undergoing surgery. Models comprising classical laboratory parameters show better accuracies (AUCs 0.92-0.93; 95% CI 0.90-0.95) compared to the use of single markers, and could easily be implemented in clinical practice by containing only readily available markers. This has been incorporated into a nomogram.

Corona and Reproduction, or Why the Corona Vaccination Does Not Result in Infertility.

Background As the COVID-19 pandemic persists and new vaccines are developed, concerns among the general public are growing that both infection with the SARS-CoV-2 virus and vaccinations against the coronavirus (mRNA vaccines) could lead to infertility or higher miscarriage rates. These fears are voiced particularly often by young adults of reproductive age. This review summarizes the current data on the impact of SARS-CoV-2 infection and corona vaccinations on female and male fertility, based on both animal models and human data. Method A systematic literature search (PubMed, Embase, Web of Science) was carried out using the search terms "COVID 19, SARS-CoV-2, fertility, semen, sperm, oocyte, male fertility, female fertility, infertility". After the search, original articles published between October 2019 and October 2021 were selected and reviewed. Results Despite the use of very high vaccine doses in animal models, no negative impacts on fertility, the course of pregnancy, or fetal development were detected. In humans, no SARS-CoV-2 RNA was found in the oocytes/follicular fluid of infected women; similarly, no differences with regard to pregnancy rates or percentages of healthy children were found between persons who had recovered from the disease, vaccinated persons, and controls. Vaccination also had no impact on live-birth rates after assisted reproductive treatment. No viral RNA was detected in the semen of the majority of infected or still infectious men; however, a significant deterioration of semen parameters was found during semen analysis, especially after severe viral disease. None of the studies found that corona vaccines had any impact on male fertility. Discussion Neither the animal models nor the human data presented in recent studies provide any indications that fertility decreases after being vaccinated against coronavirus. However, there is a growing body of evidence that severe SARS-CoV-2 infection has a negative impact on male fertility and there is clear evidence of an increased risk of complications among pregnant women with SARS-CoV-2 infection. The counseling offered to young adults should therefore take their fears and concerns seriously as well as providing a structured discussion of the current data.

Unlaid Eggs: Ovarian Damage after Low-Dose Radiation.

The total body irradiation of lymphomas and co-irradiation in the treatment of adjacent solid tumors can lead to a reduced ovarian function, premature ovarian insufficiency, and menopause. A small number of studies has assessed the radiation-induced damage of primordial follicles in animal models and humans. Studies are emerging that evaluate radiation-induced damage to the surrounding ovarian tissue including stromal and immune cells. We reviewed basic laboratory work to assess the current state of knowledge and to establish an experimental setting for further studies in animals and humans. The experimental approaches were mostly performed using mouse models. Most studies relied on single doses as high as 1 Gy, which is considered to cause severe damage to the ovary. Changes in the ovarian reserve were related to the primordial follicle count, providing reproducible evidence that radiation with 1 Gy leads to a significant depletion. Radiation with 0.1 Gy mostly did not show an effect on the primordial follicles. Fewer data exist on the effects of radiation on the ovarian microenvironment including theca-interstitial, immune, endothelial, and smooth muscle cells. We concluded that a mouse model would provide the most reliable model to study the effects of low-dose radiation. Furthermore, both immunohistochemistry and fluorescence-activated cell sorting (FACS) analyses were valuable to analyze not only the germ cells but also the ovarian microenvironment.

Sexual function in male cancer survivors is not correlated to sperm quality.

PURPOSE: Both infertility and erectile dysfunction (ED) are known long-term consequences of cancer treatment in young male cancer survivors. In the present study, we aimed to assess whether sperm quality and sexual function in male cancer survivors are associated. METHODS: In this prospective study, n = 244 patients male cancer survivors who underwent sperm analysis and cryopreservation between 2008 and 2018 prior to the initiation of gonadotoxic treatment were invited. In total n = 50 had a follow-up sperm analysis and completed two questionnaires, the Aging Males' Symptom Scale (AMS) and the International Index of Erectile Function (IIEF-EF). Differences between the individual parameters were analyzed using the Wilcoxon or Mann Whitney test. RESULTS: Azoospermia was present in n = 16/50 (32.0%) patients at time of follow-up. ED occurred in n = 9/43 (20.9%) patients and was observed more frequently in patients with oligo- or azoospermia than in those with normospermia, even though this association was not statistically significant. Sperm parameters (total sperm count, sperm concentration, progressive motility) did not differ between time of cryopreservation and time of follow-up. Mean total, somatic, psychological, and sexual AMS score was 23.6, 9.9, 6.6, and 6.8, respectively. Mean total IIEF-EF score was 27.3, indicating mainly mild ED. CONCLUSIONS: More than one-third of cancer patients suffered from azoospermia, and ED was primarily present in this subgroup. We recommend implementing the screening of sexual dysfunction in the annual sperm testing that should be offered to all men after gonadotoxic treatment. Our study highlights the importance of counseling young cancer patients on both aspects-future infertility and sexual function-prior to treatment and at follow-up visits.

Dubious effects of methadone as an "anticancer" drug on ovarian cancer cell-lines and patient-derived tumor-spheroids.

BACKGROUND: The opioid agonist D,L-methadone exerts analgesic effects via the mu opioid receptor, encoded by OPRM1 and therefore plays a role in chronic pain management. In preclinical tumor-models D,L-methadone shows apoptotic and chemo-sensitizing effects and was therefore hyped as an off-label "anticancer" drug without substantiation from clinical trials. Its effects in ovarian cancer (OC) are completely unexplored. METHODS: We analyzed OPRM1-mRNA expression in six cisplatin-sensitive, two cisplatin-resistant OC cell-lines, 170 OC tissue samples and 12 non-neoplastic control tissues. Pro-angiogenetic, cytotoxic and apoptotic effects of D,L-methadone were evaluated in OC cell-lines and four patient-derived tumor-spheroid models. RESULTS: OPRM1 was transcriptionally expressed in 69% of OC-tissues and in three of eight OC cell-lines. D,L-methadone exposure significantly reduced cell-viability in five OC cell-lines irrespective of OPRM1 expression. D,L-methadone, applied alone or combined with cisplatin, showed no significant effects on apoptosis or VEGF secretion in cell-lines. Notably, in two of the four spheroid models, treatment with D,L-methadone significantly enhanced cell growth (by up to 121%), especially after long-term exposure. This is consistent with the observed attenuation of the inhibitory effects of cisplatin in three spheroid models when adding D,L-methadone. The effect of methadone treatment on VEGF secretion in tumor-spheroids was inconclusive. CONCLUSIONS: Our study demonstrates that certain OC samples express OPRM1, which, however, is not a prerequisite for D,L-methadone function. As such, D,L-methadone may exert also detrimental effects by stimulating the growth of certain OC-cells and abrogating cisplatin's therapeutic effect.

Non-Hormonal Treatment Options for Regulation of Menstrual Cycle in Adolescents with PCOS.

Menstrual irregularities are one of the main clinical symptoms caused by polycystic ovary syndrome (PCOS). Pharmacological treatment options for non-fertility indications to restore menstrual frequency play an important role in the management of PCOS. Oral contraceptive pills are commonly prescribed for adolescents with menstrual irregularities, however, when contraindicated or poorly tolerated, further pharmacological therapy is required. This systematic literature research aims to provide an overview concerning the effects of non-hormonal pharmacological treatment options on menstrual irregularities in adolescents suffering from PCOS. A systematic literature search in PubMed, Cochrane, Embase, Bio-SISS and Web of Science was performed, including literature from January 1998 to September 2022, using specific keywords in order to find related studies. n = 265 studies were identified of which n = 164 were eligible for further evaluation. Only four placebo-controlled studies were identified, with diverging inclusion and exclusion criteria. Available data on specific non-hormonal off-label use medication primarily consisted of metformin, Glucagon-like peptide 1 receptor agonists, thiazolidinediones, anti-androgen agents (spironolactone, finasteride, flutamide) and supplements (chromium picolinate, myo-inositol). However, only a few have partly pointed out beneficial effects on improving menstrual frequency in patients diagnosed with PCOS. In summary, metformin in dosages of 1500-2550 g/day, GLP-1-analogues and supplements were effective in regulation of menstrual cycles in adolescents diagnosed with PCOS. Menstrual frequency in adolescents with PCOS is essential to prevent hypoestrogenism with long-term consequences. In this context, MET is the most effective and cost- efficient in overweight adolescent girls, also showing beneficial effects in the regulation of insulin sensitivity, especially if COCs are contraindicated or not well-tolerated. Further studies are needed to evaluate therapies in lean and normal-weight girls with PCOS.

Correlation Between Preoperative Radiological and Postoperative Pathological Tumor Size in Patients With HER2+ Breast Cancer After Neoadjuvant Chemotherapy Plus Trastuzumab and Pertuzumab.

BACKGROUND: Neoadjuvant chemotherapy (NAC) in combination with anti-HER2 treatment is standard of care in patients with early HER2 positive breast cancer. Preoperative radiological evaluation is mandatory for defining the extent of surgery. In this study, we evaluated the correlation between preoperative radiological and postoperative pathological tumor size in early HER2 positive patients after neoadjuvant chemotherapy in combination with trastuzumab and pertuzumab. In a patient population with HER2 positive breast cancer, who received neoadjuvant chemotherapy and anti-HER2 treatment, the correlation between preoperative radiological and postoperative pathological tumor size was performed. Concordance of radiological and pathological tumor size was found in 55.7%, leading to more extensive breast surgery as required in 7 cases and to the underestimation of 6 neoplastic lesions before surgery, respectively. PATIENTS AND METHODS: Seventy early HER2 positive breast cancer patients were included and retrospectively analysed. All preoperative radiological assessments as well as the tumor board decision on surgical extent and pathological evaluation were completed at the Medical University of Vienna. Preoperative radiological assessment of tumor size and lymph node status were compared with final histopathological findings. The correlation between different radiological modalities regarding tumor size was investigated. RESULTS: Concordance of radiological and pathological tumor size was found in 55.7 % (50% by sonography and 66.7% by MRI, respectively) of patients with a nonsignificant correlation of r = 0.31 (P = .08). Of the 39 patients with pathologic complete remission (pCR), 16 were also classified as radiological complete response (rCR) while 23 of those showed a radiological stable disease or partial response. In 6 patients, radiological assessment showed a CR but invasive cancer with a tumor size range from 7 to 36 mm was found in histopathological examination. Neither menopausal status (P= .69) nor BMI (P = .60) and age (P = .50) had an impact on the correlation between radiological and histopathological tumor size. Regarding lymph node status, a statistically significant association and clinically relevant correlation between radiological and histopathological evaluation was found (r = 0.66, P < .001). CONCLUSION: Concordance between radiology and histopathology was low regarding tumor size after NAC in combination with trastuzumab and pertuzumab, but significant regarding lymph node status.

The impact of COVID-19 pandemic on the rate of newly diagnosed gynecological and breast cancers: a tertiary center perspective.

PURPOSE: The aim of the present study was to assess the impact of postponed screening examinations and lockdown measures on gynecological and breast cancer diagnoses throughout the year 2020 in a gynecological oncological center in Austria. METHODS: Data of 889 patients with either newly diagnosed gynecological or breast cancer between January 2019 and December 2020 were collected. Clinical parameters including symptoms, performance status, comorbidities and referral status were compared in patients, who were newly diagnosed with cancer in the period of the first lockdown from March 2020 to April 2020 and the second lockdown from November 2020 to December 2020 and compared to the same period in 2019. RESULTS: Our results showed a strong decline in newly diagnosed cancers during the lockdown periods: -45% in gynecological cancer and -52% in breast cancer compared to the same period in 2019. Compared to the analogue period of 2019, breast cancer patients reported significantly more tumor-associated symptoms (55% vs. 31%, p = 0.013) during and in between (48% vs. 32%, p = 0.022) the lockdowns. During the lockdown, periods in the group of breast cancer patients' tumor stage varied significantly compared to 2019 (T2-T4; p = 0.047). CONCLUSION: Both lockdowns led to a strong decrease in newly diagnosed gynecological and breast cancers. Treatment delays in potentially curable disease could lead to inferior clinical outcomes, with the risk of missing the optimal treatment window. As the COVID-19 pandemic will be a challenge for some time to come, new strategies in patient care are needed to optimize cancer screening and management during the pandemic.

Sperm banking before gonadotoxic treatment: is it worth the effort?

We aimed to compare the sperm quality in different cancer types and benign diseases before gonadotoxic treatment, and assess the usage rate of cryopreserved sperm for assisted reproductive treatment (ART). This retrospective study was conducted at two university clinics between January 2008 and July 2018. A total of 545 patients suffering from cancer or benign diseases were included in the study. The pretreatment sperm analyses were based on the World Health Organization (WHO) guidelines. Patients with testicular malignancy (TM) showed a significantly lower sperm count (median [interquartile range]: 18.7 × 106 [5.3 × 106-43.0 × 106] ml-1; P = 0.03) as well as total sperm count (42.4 × 106 [13.3 × 106-108.5 × 106] per ejaculate; P = 0.007) compared to other malignant and benign diseases. In addition, patients with nonseminomatous TM showed the lowest sperm count (14.3 × 106 [6.0 × 106-29.9 × 106] ml-1, vs seminomas: 16.5 × 106 [4.6 × 106-20.3 × 106] ml-1; P = 0.001). With reference to the WHO 2010 guidelines, approximately 48.0% of the patients with TM and 23.0% with hematological malignancies (HM) had oligozoospermia. During the observation period, only 29 patients (5.3%) used their frozen sperms for 48 ART cycles, resulting in 15 clinical pregnancies and 10 live births. The sperm quality varies with the type of underlying disease, with TM and HM patients showing the lowest sperm counts. Due to the observed low usage rate of cryopreserved sperm, further patient interviews and sperm analyses should be included in the routine oncologic protocols to avoid unnecessary storage expenses. However, sperm banking is worth the effort as it provides hope for men who cannot reproduce naturally after gonadotoxic treatment.

Impact of frailty on the management of patients with gynecological cancer aged 80 years and older.

PURPOSE: To assess the impact of frailty on compliance of standard therapy, complication, rate and survival in patients with gynecological malignancy aged 80 years and older. METHODS: In total, 83 women with gynecological malignancy (vulva, endometrial, ovarian or cervical cancer) who underwent primary treatment between 2007 and 2017 were retrospectively analyzed. Frailty index was calculated and its association with compliance of standard treatment, peri- and postoperative mortality and morbidity, and survival was evaluated. RESULTS: Frailty was observed in 24.1% of cases. Both frail and non-frail patients were able to receive standard therapy in most cases - 75.0% and 85.7%, respectively (p = 0.27). Frail patients did not show an increased postoperative complication rate. Frail patients had shorter 3 years overall survival rates (28%) when compared to non-frail patients (55%) (p = 0.02). In multivariable analysis high frailty index (Hazard Ratio [HR] 12.15 [1.39-106.05], p = 0.02) and advanced tumor stage (HR 1.33 [1.00-1.76], p = 0.05) were associated with poor overall survival, but not age, histologic grading, performance status, and compliance of standard therapy. CONCLUSION: Majority of patients was able to receive standard therapy, as suggested by the tumor board, irrespective of age and frailty. Nonetheless, frailty is a common finding in patients with gynecological malignancy aged 80 years and older. Frail patients show shorter progression-free, and overall survival within this cohort.

Decrease in gynecological cancer diagnoses during the COVID-19 pandemic: an Austrian perspective.

BACKGROUND: On March 16, 2020, the federal government of Austria declared a nationwide lockdown due to the COVID-19 pandemic. Since the lockdown, screening examinations and routine checkups have been restricted to prevent the spread of the virus and to increase the hospitals' bed capacity across the country. This resulted in a severe decline of patient referrals to the hospitals. OBJECTIVE: To assess the impact of the COVID-19 pandemic on the rate of newly diagnosed gynecological and breast cancers in Austria. METHODS: Data of 2077 patients from 18 centers in Austria with newly diagnosed gynecological or breast cancer between January and May 2019 and January and May 2020 were collected. Clinical parameters, including symptoms, performance status, co-morbidities, and referral status, were compared between the time before and after the COVID-19 outbreak. RESULTS: Our results showed a slight increase of newly diagnosed cancers in January and February 2020 as compared with 2019 (+2 and +35%, respectively) and a strong decline in newly diagnosed tumors since the lockdown: -24% in March 2020 versus March 2019, -49% in April 2020 versus April 2019, -49% in May 2020 versus May 2019. Two-thirds of patients diagnosed during the pandemic presented with tumor-specific symptoms compared with less than 50% before the pandemic (p<0.001). Moreover, almost 50% of patients in 2020 had no co-morbidities compared with 35% in 2019 (p<0.001). Patients, who already had a malignant disease, were rarely diagnosed with a new cancer in 2020 as compared with 2019 (11% vs 6%; p<0.001). CONCLUSIONS: The lockdown led to a decreased number of newly diagnosed gynecological and breast cancers. The decreased accessibility of the medical services and postponed diagnosis of potentially curable cancers during the COVID-19 pandemic may be a step backwards in our healthcare system and might impair cancer treatment outcomes. Therefore, new strategies to manage early cancer detection are needed to optimize cancer care in a time of pandemic in the future.

Early onset of menopause is associated with increased peripheral atherosclerotic plaque volume and progression.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) is the leading cause of death in western countries. One risk factor unique to women is the menopausal status. The aim of this study was to analyse the influence of the onset of menopause (MP) on the extent and progression of atherosclerotic plaque volume (PV). METHODS: Postmenopausal women with at least one cardiovascular risk factor (CVRF) but without established CVD were included. Quantification of PV was performed in peripheral arteries using a three - dimensional (3D) ultrasound (US) technique. Follow-up examination to assess PV progression was performed after 19 (±8) months. RESULTS: 110 consecutive postmenopausal women (mean age 65.5) were included. Females with an earlier onset of MP (<45 years) had a significantly higher PV than those with an intermediate (45-52 years) or later onset of menopause (>52 years), irrespective of other CVRF (244 mm³ vs. 193 mm³ vs. 73 mm³, respectively, p = 0.023). In addition, women with an earlier onset of MP had a higher PV progression compared to women with an intermediate or late onset (40 mm³ vs. 35 mm³ vs. 8.5 mm³; p = 0.002, respectively). Moreover, these results were confirmed in multivariate regression, where only onset of MP (OR 0.88; 95%CI 0.81-0.96; p = 0.004) and age (OR 1.06; 95%CI 1.08-1.13; p = 0.025) were significant predictors for a higher atherosclerotic progression. CONCLUSIONS: An earlier onset of MP was associated with an increase in atherosclerotic PV and accelerated progression, independent of other CVRF.

Gamma-glutamyltransferase as a preoperative differential diagnostic marker in patients with adnexal mass.

OBJECTIVE: Gamma-glutamyltransferase (GGT) is involved in tumor development, progression and chemotherapy resistance. The present study evaluated GGT serum levels as a preoperative predictive marker for ovarian cancer in patients with adnexal mass. STUDY DESIGN: Preoperative GGT serum levels of 2235 patients with adnexal mass and subsequent surgery were ascertained (patients with benign ovarian tumors: n = 1811; borderline tumor of the ovary [BTO]: n = 85; epithelial ovarian cancer [EOC]: n = 339). Standardized expert transvaginal ultrasound was documented. RESULTS: Median (interquartile range) GGT serum levels in patients with benign ovarian tumors, BTO, and EOC were 15.0 U/l (11.0-23.0), 17.0 U/l (10.0-23.5), and 20.0 U/l (13.0-34.0), respectively (p = 0.002). Elevated GGT serum levels were associated with the presence of BTO/EOC in univariate analysis (p < 0.0001, hazard ratio 1.8, confidence interval 1.5-2.3). GGT did not outperform established tools for preoperative prediction of BTO/EOC in patients with adnexal mass, such as CA-125 measurement or transvaginal ultrasound. CONCLUSION: Elevated GGT serum levels were not associated with the presence of BTO/EOC in women with suspicious adnexal mass in multivariate analysis. GGT serum levels did not outperform established risk factors and therefore might add only limited additional value to CA-125 serum levels in the differential diagnosis between benign and malignant adnexal masses.

Long-term functional and structural preservation of precision-cut human myocardium under continuous electromechanical stimulation in vitro.

In vitro models incorporating the complexity and function of adult human tissues are highly desired for translational research. Whilst vital slices of human myocardium approach these demands, their rapid degeneration in tissue culture precludes long-term experimentation. Here, we report preservation of structure and performance of human myocardium under conditions of physiological preload, compliance, and continuous excitation. In biomimetic culture, tissue slices prepared from explanted failing human hearts attain a stable state of contractility that can be monitored for up to 4 months or 2000000 beats in vitro. Cultured myocardium undergoes particular alterations in biomechanics, structure, and mRNA expression. The suitability of the model for drug safety evaluation is exemplified by repeated assessment of refractory period that permits sensitive analysis of repolarization impairment induced by the multimodal hERG-inhibitor pentamidine. Biomimetic tissue culture will provide new opportunities to study drug targets, gene functions, and cellular plasticity in adult human myocardium.