[Delayed-Interval Delivery of an Extremely Preterm Twin after Abort of the First Twin and Emergency Total Cervical Occlusion at 19+1 Weeks of Gestation - a Case Report]. / Verlauf eines frühgeborenen Geminus nach totalem Muttermundsverschluss bei Spontanabort des ersten Geminus in der 19+1 Schwangerschaftswoche ­ Fallbericht und Literaturübersicht.

We report on the obstetric and neonatal course of a 34-year-old woman pregnant with twins, who presented at our clinic at 16+1 weeks of gestation with preterm premature rupture of membranes. We started intravenous antibiotic therapy with inpatient monitoring owing to the vitality and regular development of both twins, with anhydramnios in the leading twin. After a missed abortion of the leading twin at 19+1 weeks of gestation we decided on surgical intervention with assisted delivery of the aborted twin, leaving the placenta in situ with subsequent emergency total cervical occlusion. Afterwards, the single pregnancy could be continued until the 24th week of gestation. An urgent Caesarean section for early labor, premature rupture of membranes, and increasing signs of maternal infection was later performed. Overall, the postnatal course of the extremely preterm neonate was a success considering the gestational age. We conclude that the option of surgical interventions should be taken into account in similar cases in the future.

Comparison of Vaginal Pessaries to Standard Care or Pelvic Floor Muscle Training for Treating Postpartum Urinary Incontinence: a Pragmatic Randomized Controlled Trial.

Introduction: To compare three conservative treatment options, standard care, pelvic floor muscle training (PFMT), and vaginal pessaries, for postpartum urinary incontinence (UI) that are accessible to most patients and practitioners in a generalizable cohort. Materials and Methods: A multicenter, open-label, parallel group, pragmatic randomized controlled clinical trial comparing standard care, PFMT, and vaginal cube pessary for postpartum urinary incontinence was conducted in six outpatient clinics. Sample size was based on large treatment effects (Cramers' V > 0.35) with a power of 80% and an alpha of 0.05 for a 3 × 3 contingency table, 44 patients needed to be included in the trial. Outcomes were analyzed according to the intention-to-treat principle. Group comparisons were made using analysis of variance (ANOVA), Kruskal-Wallis, and chi-square test as appropriate. P < 0.05 was considered statistically significant. Results: Of the 516 women screened, 111 presented with postpartum UI. Of these, 52 were randomized to one of three treatment groups: standard care (n = 17), pelvic floor muscle training (n = 17), or vaginal cube pessary (n = 18). After 12 weeks of treatment, treatment success, as measured by patient satisfaction, was significantly higher in the vaginal pessary group (77.8%, n = 14/18), compared to the standard care group (41.2%, n = 7/17), and the PFMT (23.5%, n = 4/17; χ 2 2,n = 52  = 14.55; p = 0.006, Cramer-V = 0.374). No adverse events were reported. SUI and MUI accounted for 88.4% of postpartum UI. Conclusion: Vaginal pessaries were superior to standard care or PFMT to satisfyingly reduce postpartum UI symptoms. No complications were found.

Subcutaneous injection of trastuzumab into the thigh versus abdominal wall in patients with HER2-positive early breast cancer: Pharmacokinetic, safety and patients' preference - Substudy of the randomised phase III GAIN-2 study.

BACKGROUND: Trastuzumab given intravenously in combination with chemotherapy is standard of care for patients with early HER2-positive breast cancer (BC). Different randomised studies have shown equivalent efficacy of a subcutaneous injection into the thigh compared to the intravenous formulation. Other body regions for injection have not been investigated but might be more convenient for patients. METHODS: After surgery, patients were randomised to receive either subcutaneous trastuzumab into the thigh or into the abdominal wall (AW). Patient preferences were evaluated using validated questionnaires (PINT). Primary objectives of this multicentre, non-blinded, randomised substudy of the GAIN-2 study were to investigate pharmacokinetics of the injection into the thigh versus AW and to determine patients' preferences of either administration site versus the previously received intravenous application. RESULTS: 226 patients were randomised and 219 patients (thigh: N = 110; AW: N = 109) formed the modified intent-to-treat (mITT). Overall, 83.5% (out of N = 182 with information about patients' preference) preferred subcutaneous over previous intravenous application or had no preference. Preference was similar between both administration sites (thigh: 80.6%; AW: 86.5; p = 0.322). Pharmacokinetic analysis included 30 patients. Geometric means of Cmax and AUC0-21d were higher in thigh than in AW group (geometric mean ratio with body weight adjustment: Cmax: 1.291, 90%-CI 1.052-1.584; AUC0-21d: 1.291, 90%-CI 1.026-1.626). Safety profile was in line with previous reports of subcutaneous trastuzumab. CONCLUSION: Subcutaneous trastuzumab into the thigh showed an approximately 30% higher bioavailability. Injections were well tolerated and preferred over intravenous administration. The subcutaneous injection into the thigh should remain the standard of care.

Sexual Disorders in Women with Overactive Bladder and Urinary Stress Incontinence Compared to Controls: A Prospective Study.

Introduction and Hypothesis Female urinary incontinence (UI) has a negative impact on sexual function and sexual quality of life (QoL) in women. But there is still no consensus on the type of UI or the prevalence of sexual dysfunction (SD). The aim of the study was to evaluate sexual disorders in women with overactive bladder (OAB) compared to patients with urinary stress incontinence (SUI) and healthy controls. Materials and Methods 106 women presenting to a urogynecological outpatient clinic (referral clinic) were investigated using standardized questionnaires and the Female Sexual Function Index (FSFI-d). All 65 incontinent women underwent a full urodynamic examination; the controls (31) were non-incontinent women in the same age range who came for routine check-ups or minor disorders not involving micturition or pelvic floor function. Women with mixed urinary incontinence, a history of previous medical or surgical treatment for UI, recurrent urinary tract infections, previous radiation therapy or pelvic organ prolapse of more than stage 2 on the Pelvic Organ Prolapse Quantification (POP-Q) system were excluded. Results 100 questionnaires could be evaluated (94.3%). Thirty-four women had urinary stress incontinence, 35 had OAB, 31 were controls. Mean age was 56 years, with no significant differences between groups. The scores of the questionnaire ranged from 2 to 35.1 points. The median score of OAB patients was significantly lower (17.6) than the median score of the controls (26.5; p = 0,004). The stress-incontinent women had a score of 21.95, which was lower than that of the controls but statistically non-significant (p = 0.051). In all subdomains, the OAB patients had lower scores than the stress-incontinent women and significantly lower values than the control group. Most striking was the impairment of "sexual interest in the last 4 weeks". The figure for "none or almost no sexual activity" was 80% for the OAB group, 64.7% for the group of stress-incontinent women and 48% for the control group. Incontinence during intercourse was reported by one OAB patient and 4 stress-incontinent women but did not occur in the control group. Conclusions There is a high prevalence of SD in women with urinary incontinence. Patients with OAB reported a greater negative impact on sexual function and had significantly lower scores for the FSFI questionnaire than patients with stress incontinence or controls.

Resumption of Trastuzumab in Patients With Disease Recurrence After (Neo-) Adjuvant Anti-HER2-therapy in Patients With HER2-positive Breast Cancer.

BACKGROUND/AIM: HER2-positive breast cancers eventually relapse in about one third of patients. Is anti-HER2-directed therapy with Herceptin® (trastuzumab) effective in re-treatment? Between 2008 and 2018, 216 patients with recurrent HER2-positive breast cancer (BC) were re-treated with Herceptin (HER) during first-line therapy. This study assessed the effectiveness and tolerability of re-treatment with HER. PATIENTS AND METHODS: After approval from Ethical committee, the NIS was conducted according to German Drug Act. Re-treatment with HER was documented at routine visits starting with a basic observational period of maximum 12 months and a follow-up period of maximum additional four years. RESULTS: HER2-positive BC relapsed after a median of 36.5 months (mos). Patients were re-treated with HER +/- chemotherapy +/- endocrine therapy. HER-containing regimens resulted in median progression-free survival (mPFS) of 12.7 (95%CI=10.5-14.8) mos and overall survival (OS-2) of 31.6 mos (95%CI=28.8-38.4) since recurrence diagnosis. Differentiation of recurrence types (local, visceral, non-visceral) unfolded worst prognosis for patients with visceral metastases. Cardiac monitoring within this non-interventional study (NIS) did not result in new safety concerns. CONCLUSION: Re-therapy with HER in the first-line setting of advanced HER2-positive breast cancer is effective and without unexpected or intensified adverse events.

Implementation of the Recommendation to Vaccinate Pregnant Women against Seasonal Influenza - Vaccination Rates and Acceptance.

Introduction In Germany vaccination recommendations are revised annually and published by the Standing Committee on Vaccination at the Robert Koch Institute (STIKO). In 2010 the vaccination recommendations were amended to include the proposal that pregnant women in the 2nd trimester of pregnancy and pregnant women with additional underlying disease in the 1st trimester of pregnancy should be vaccinated against seasonal influenza. This paper reports on vaccination rates and the factors influencing them. Method A cross-sectional study was carried out in two level 1 perinatal centers in two different German federal states (Saarland and Rhineland-Palatinate) during the influenza seasons of 2012/2013 and 2013/2014. A total of 253 pregnant women were included in the study. Pregnant women were interviewed using a standardized, pre-tested questionnaire and asked whether they were aware of the recommendation to vaccinate against seasonal influenza and about possible factors which might influence their decision to be vaccinated. In addition, data from their vaccination certificates and pregnancy passports were evaluated. Results Overall, the records of only 19.5 % of the pregnant women showed that they had been vaccinated against influenza in pregnancy. Among the group of pregnant women who had a previous history of vaccinations against influenza the willingness to be vaccinated was high (43.3 %) and this figure was statistically significant. The vaccination rate was even higher (49.9 %) and even more statistically significant among pregnant women whose gynecologist or family physician had recommended that they should be vaccinated. In contrast, only 3.3 % of pregnant women who had not been given the recommendation to vaccinate by their physicians were vaccinated against influenza. Discussion The failure to recommend that pregnant women be vaccinated against influenza and women's lack of any previous experience of influenza vaccination were the main reasons for the inadequate influenza vaccination coverage in pregnancy. Conclusion One of the key points to increase the influenza vaccination rate is to intensify the counselling of the pregnant women through the gynecologist.

Subclinical Myocardial Impairment Occurred in Septal and Anterior LV Wall Segments After Anthracycline-Embedded Chemotherapy and did not Worsen During Adjuvant Trastuzumab Treatment in Breast Cancer Patients.

In a previous study of breast cancer patients, we found changes in cardiac function and size during the early stages of adjuvant trastuzumab (Herceptin(®)) therapy. Here we present a subgroup analysis of this patient cohort. This subgroup received a anthracycline-embedded chemotherapy followed by at least 3 months up to 6 months of adjuvant Herceptin(®) therapy. Twenty-seven female breast cancer patients with Her-2/-neu overexpression were studied using conventional echocardiography and 2D speckle tracking. These methods were done before anthracycline-embedded chemotherapy, before adjuvant trastuzumab therapy, and both 3 and 6 months after the start of the therapy (T3, T6). The LV-EF (Simpson biplane) decreased significantly from before the chemotherapy to after the chemotherapy and further decreased after 3 months of trastuzumab therapy (66.2 ± 1.5 vs. 58.7 ± 1.2 vs. 55.6 ± 1.3 vs. 55.9 ± 1.5 %; p < 0.05). The stroke volume index remained constant after chemotherapy (22.0 ± 0.8 vs. 22.6 ± 1.3 ml/m(2); p = 0.9), but increased significantly during trastuzumab therapy (26.7 ± 1.1 and 27.3 ± 1.0 ml/m(2); p < 0.01). Global longitudinal strain exclusively decreased during chemotherapy (-21.0 ± 0.5 vs. -18.9 ± 0.5 %, p < 0.001). Regional longitudinal strain decreased significantly after chemotherapy in septal, anteroseptal, anterolateral, and apex segments. Mitral valve regurgitation increased during the whole treatment, but especially during trastuzumab. Right ventricular function decreased exclusively during chemotherapy. Anthracycline-embedded chemotherapy in patients with breast cancer led to a decrease in LV function, especially of the septal and anterior segments, and did not worsen during adjuvant trastuzumab treatment.

Echocardiography signs of early cardiac impairment in patients with breast cancer and trastuzumab therapy.

OBJECTIVE: Recent studies in breast cancer patients and Trastuzumab therapy (Herceptin) showed a development of a toxic cardiomyopathy as a severe complication. The aim of this study was to discover early changes in cardiac function and morphology. METHODS: We studied 42 female patients with Her-2/-neu over-expression in breast cancer by echocardiography before, 3, and 6 months after start of the adjuvant Herceptin therapy. All values were mean value ± standard deviation. RESULTS: After 3 or 6 months of a trastuzumab therapy we discovered significant increases in the diastolic and systolic left ventricle volume indices (LV-DVI 32.4 ± 8.5 vs. 38.5 ± 8.7 vs. 40.3 ± 10.3 ml/m², p < 0.001 and LV-SVI 12.6 ± 4.0 vs. 15.7 ± 4.7 vs. 17.2 ± 6.8 ml/m², p < 0.001), an increase of the end-diastolic and end-systolic LV diameter (LVEDD 46.8 ± 4.2 vs. 48.0 ± 4.7 vs. 49.7 ± 4.5 ml/m², p < 0.01; LVESD 28.3 ± 4.2 vs. 31.0 ± 4.7 vs. 32.3 ± 4.9 mm, p < 0.001), a reduced systolic ventricle function determined by the tissue Doppler imaging (TDI) velocity (9.2 ± 2.5 vs. 8.0 ± 1,7 vs. 7.7 ± 1.5 cm/s, p < 0.001), fractional shortening (39,6 ± 7.5 vs. 35.4 ± 7.4 vs. 35.2 ± 7.0%, p < 0.01), and the LV-EF Simpson biplane [62.0 ± 5.1 vs. 60.1 ± 6.3 (p = ns) vs. 58.4 ± 7.9%, p < 0.01] compared to pretreatment values. There was also an increase of the left atrial volume index (21.4 ± 6.2 vs. 26.2 ± 7.9 vs. 29.7 ± 8.8 ml/m², p < 0.001), a decrease of the median TDI atrial velocities (11.9 ± 2.4 vs. 10.5 ± 2.8 vs. 10.1 ± 2.1 cm/s, p < 0.01), an increase of the peak early diastolic filling velocities (73.1 ± 15.4 vs. 83.1 ± 16.4 vs. 82.2 ± 19.4 cm/s, p < 0.05), and an increase of the median mitral valve insufficiency degree (0.64 ± 0.65 vs. 1.03 ± 0.76 vs. 1.11 ± 0.73°, p < 0.001). We could not detect a significant increase in diastolic dysfunction. Also right heart diameters and function did not change significantly. Most patients stayed in an asymptomatic stage of cardiac disease. CONCLUSION: The blockade of Her2/-neu receptors with trastuzumab in patients with breast cancer led to measurable alterations of left ventricular volume, left atrial volume, and systolic function as early as 3 months after start of treatment.