Thorsten Fischer

Pregnancy‐induced sympathetic overactivity: a precursor of preeclampsia*

Background  Preeclampsia has been shown to constitute a state of sympathetic overactivity. However, it remains unclear if the sympathetic activity precedes preeclampsia or represents only a secondary phenomenon. To further investigate this issue, we performed a prospective study in pregnant women considered to be at increased risk for preeclampsia owing to preeclampsia during a preceding pregnancy.

Effect of Pregnancy on Long‐Term Kidney Function in Renal Transplant Recipients Treated with Cyclosporine and with Azathioprine

In order to investigate the effect of different immunosuppressive regimens and the time interval between transplantation and pregnancy on long‐term outcome, we performed a case‐control study in pregnant renal allograft recipients. Eighty‐one pregnancies of kidney transplanted recipients were identified [cyclosporine (CYA): n = 40; azathioprine (AZA): n = 41]. Controls were matched with respect to important prognostic factors. Posttransplant follow‐up was 91.3 ± 5 months. Graft and patient survival were similar in both groups and there was no apparent effect of immunosuppression. A total of 28 recipients (33%) delivered within 2 years and 6 (8%) subjects within 1 year after transplantation, but these short transplantation‐to‐pregnancy intervals had no apparent adverse effect on long‐term outcome. In contrast to AZA‐treated patients, CYA‐treated patients experienced an increase in serum creatinine postpartum (1.15 ± 0.2 mg/dL vs. 1.61 ± 0.1 mg/dL; p < 0.05). Whole blood CYA levels decreased transiently during pregnancy from 115.9 ± 8 ng/mL to 80.7 ± 7 ng/mL leading to a gradual increase in drug dose from 240 ± 14 mg/day to 324 ± 21 mg/day (p < 0.05). Following delivery, there was an increase in CYA concentrations to 173 ± 5.4 ng/mL, requiring rapid dose tapering to baseline of 246 ± 15 mg/day. Pregnancies in renal recipients do not affect long‐term patient and graft survival, independent of the immunosuppression. No detrimental effect of short transplantation‐to‐pregnancy intervals on long‐term graft function was detected.

The Maternal Brain: An Organ with Peripartal Plasticity

The time of pregnancy, birth, and lactation, is characterized by numerous specific alterations in several systems of the maternal body. Peripartum-associated changes in physiology and behavior, as well as their underlying molecular mechanisms, have been the focus of research since decades, but are still far from being entirely understood. Also, there is growing evidence that pregnancy and lactation are associated with a variety of alterations in neural plasticity, including adult neurogenesis, functional and structural synaptic plasticity, and dendritic remodeling in different brain regions. All of the mentioned changes are not only believed to be a prerequisite for the proper fetal and neonatal development, but moreover to be crucial for the physiological and mental health of the mother. The underlying mechanisms apparently need to be under tight control, since in cases of dysregulation, a certain percentage of women develop disorders like preeclampsia or postpartum mood and anxiety disorders during the course of pregnancy and lactation. This review describes common peripartum adaptations in physiology and behavior. Moreover, it concentrates on different forms of peripartum-associated plasticity including changes in neurogenesis and their possible underlying molecular mechanisms. Finally, consequences of malfunction in those systems are discussed.

Takayasu’s arteritis in pregnancy: review of literature and discussion

Abstract Takayasus arteritis (TA) is a rare inflammatory disease of the arteries that affects women of childbearing age. The optimal management for pregnant patients with this disease has not yet been defined. The course of disease seems to be neither affected nor worsened by pregnancy. We could not find reported maternal deaths directly related to pregnancy. However, many authors report maternal as well as fetal unfavorable events in the course of pregnancy. We describe a 25-year-old primigravida of Turkish-Greek origin who presented at 30 weeks of pregnancy with active TA. In the 37th week, intrauterine fetal death occurred. Our patient did not show high blood pressure or aortic inflammation. The course of her disease was stable. Whether a newly diagnosed TA during pregnancy should be regarded as an indication for premature delivery is discussed. An interdisciplinary collaboration of rheumatologists, nephrologists and obstetricians is necessary to improve maternal and fetal prognosis.

The impact of breast cancer awareness and socioeconomic status on willingness to receive breast cancer prevention drugs.

PurposeTo find associations between knowledge about risk factors for breast cancer and the socioeconomic status of healthy women, as well as their attitude toward taking chemopreventive drugs.Patients and methodsBetween April and September 1999, 7135 healthy women completed questionnaires providing information about their willingness to take chemopreventive drugs. Items in the questionnaire included the sources of the information they had, their estimates of the population and personal lifetime risk, and risk factors for breast cancer.ResultsA total of 6597 questionnaires were evaluable. The responders’ median age was 44. Fifty-five percent of the women were willing to consider receiving chemopreventive drugs to lower their risk for breast cancer. Participants who estimated the population risk as being very high were more disposed to receive chemoprevention (65.3%), as were women who estimated their own breast cancer risk as being high (74.1%). A family history of breast cancer only had a low impact on willingness to receive chemoprevention. Women with a family history of breast cancer were willing to take chemopreventive agents in 57.2% of cases. The multivariate analysis showed that knowing about risk factors and having a lower educational level were factors positively correlated with willingness to consider chemoprevention.ConclusionThese findings emphasize the role of estimations of the risk of breast cancer for patients considering whether to accept chemoprevention treatment. To date, only a few modern models of risk estimation have been evaluated in relation to chemoprevention. There is a need for better integration of professional risk estimations into clinical practice.

IOERT as anticipated tumor bed boost during breast-conserving surgery after neoadjuvant chemotherapy in locally advanced breast cancer--results of a case series after 5-year follow-up.

To evaluate retrospectively rates of local (LCR) and locoregional tumor control (LRCR) in patients with locally advanced breast cancer (LABC) who were treated with preoperative chemotherapy (primary systemic treatment, PST) followed by breast‐conserving surgery (BCS) and either intraoperative radiotherapy with electrons (IOERT) preceding whole‐breast irradiation (WBI) (Group 1) or with WBI followed by an external tumor bed boost (electrons or photons) instead of IOERT (Group 2). From 2002 to 2007, 83 patients with clinical Stage II or III breast cancer were enrolled in Group 1 and 26 in Group 2. All patients received PST followed by BCS and axillary lymph node dissection. IOERT boosts were applied by single doses of 9 Gy (90% reference isodose) versus external boosts of 12 Gy (median dose range, 6–16) in 2 Gy/fraction (ICRU). WBI in both groups was performed up to total doses of 51–57 Gy (1.7–1.8 Gy/fraction). The respective median follow‐up times for Groups 1 and 2 amount 59 months (range, 3–115) and 67.5 months (range, 13–120). Corresponding 6‐year rates for LCR, LRCR, metastasis‐free survival, disease‐specific survival and overall survival were 98.5, 97.2, 84.7, 89.2 and 86.4% for Group 1 and 88.1, 88.1, 74, 92 and 92% for Group 2, respectively, without any statistical significances. IOERT as boost modality during BCS in LABC after PST shows a trend to be superior in terms of LCR and LRCR in comparison with conventional boosts.

Advanced Metastatic Melanoma during Pregnancy: A Multidisciplinary Challenge

Background: Metastatic melanoma during pregnancy represents a life-threatening situation not only for the mother but also for the fetus due to aggressive therapy and potential maternal-fetal metastasis. Case Report: We report the case of a 37-year-old woman with advanced metastatic malignant melanoma during her first pregnancy, with a review of the literature. In this case, a tight and primarily interdisciplinary obstetrical and dermatological case management enabled the delivery of a small but healthy premature infant in the 29th week of gestation by planned Cesarean section. However, due to progressive disease, the mother died only 10 weeks after the delivery of the baby. Conclusion: Sufficient perinatal and oncologic experience provided, diagnostic and surgical interventions as well as radiotherapy and chemotherapy in metastatic melanoma disease are feasible and relatively safe even during pregnancy.

Physician-based active cost management of oncological therapies reducing pharmaceutical costs by 83.4% in two years without leaving standard of care

We report about the 2-year results of a physician-based active cost management model for oncological therapies in a German OB/GYN university clinic. Over 2 years more than 4,000 oncological cycles were prospectively and individually analyzed regarding costs and reimbursement mode. Main aim was reducing costs without lowering cycle number and standard of care. Within two years pharmaceutical costs were reduced by 83.4% or 785,976.- EUR. All causes for a previous financial loss were identified and eliminated. Debts were paid back and employment of new staff and investments were possible. With this first active cost management model by and for physicians, oncological therapies can be performed cost covering even in a university clinic. Although developed for optimization of cost coverage of oncological therapies in Germany, this model is universally transferable.

The Reliability of Fetal MRI in the Assessment of Brain Malformations

Objectives: To assess the inter- and intraobserver reliability of different fetal MRI measurements in cases of fetal brain malformations and to examine the concordance between ultrasonography (US) and MRI findings. Methods: Fetal brain MRIs and US findings of 56 pregnant women were retrieved from the institutional database. Standardized fetal brain MRI measurements were performed by 4 observers, and the inter- and intraobserver reliability was determined. Additionally, US and MRI findings were retrospectively compared. Results: The interobserver intraclass correlation coefficient (ICC) was above 0.9 for the cerebellum and posterior horn of the lateral ventricle. The measurements regarding the third ventricle (0.50), the fourth ventricle (0.58), and the corpus callosum (0.63) showed poor reliability. Overall, the intraobserver reliability was greater than the interobserver reliability. US and MRI findings were discordant in 29% of the cases with MRI rendering an extended diagnosis in 18%, a change of diagnosis in 3.6%, and excluding pathological findings suspected on US in 7.1%. Conclusions: Fetal MRI is a valuable complement to US in the investigation of fetal brain malformations. The reliability of most parameters was high, except for the measurements of the third and fourth ventricles and the corpus callosum.

Relevance of Health Economics in Breast Cancer Treatment: Integration of Economics in the Management of Breast Cancer at the Clinic Level

Since the introduction of the diagnosis-related groups (DRG) system with cost-related and entity-specific flat-rate reimbursements for all in-patients in 2004 in Germany, economics have become an important focus in medical care, including breast centers. Since then, physicians and hospitals have had to gradually take on more and more financial responsibilities for their medical care to avoid losses for their institutions. Due to financial limitations of resources, most medical services have to be adjusted to correlating revenues, which results in the development of a variety of active measures to understand, steer, and optimize costs, resources and related processes for breast cancer treatment. In this review, the challenging task to implement microeconomic management at the clinic level for breast cancer treatment is analyzed from breast cancer-specific publications. The newly developed economic management perspective is identified for different stakeholders in the healthcare system, and successful microeconomic projects and future aspects are described.