[Show abstract][Hide abstract] ABSTRACT: Background:
Pooled human platelet lysate (pHPL) is an efficient alternative to xenogenic supplements for ex vivo expansion of mesenchymal stem cells (MSCs) in clinical studies. Currently, porcine heparin is used in pHPL-supplemented medium to prevent clotting due to plasmatic coagulation factors. We therefore searched for an efficient and reproducible medium preparation method that avoids clot formation while omitting animal-derived heparin.
We established a protocol to deplete fibrinogen by clotting of pHPL in medium, subsequent mechanical hydrogel disruption and removal of the fibrin pellet. After primary culture, bone-marrow and umbilical cord derived MSCs were tested for surface markers by flow cytometry and for trilineage differentiation capacity. Proliferation and clonogenicity were analyzed for three passages.
The proposed clotting procedure reduced fibrinogen more than 1000-fold, while a volume recovery of 99.5 % was obtained. All MSC types were propagated in standard and fibrinogen-depleted medium. Flow cytometric phenotype profiles and adipogenic, osteogenic and chondrogenic differentiation potential in vitro were independent of MSC-source or medium type. Enhanced proliferation of MSCs was observed in the absence of fibrinogen but presence of heparin compared to standard medium. Interestingly, this proliferative response to heparin was not detected after an initial contact with fibrinogen during the isolation procedure.
Here, we present an efficient, reproducible and economical method in compliance to good manufacturing practice for the preparation of MSC media avoiding xenogenic components and suitable for clinical studies.
Journal of Translational Medicine 11/2015; 13(1):354. DOI:10.1186/s12967-015-0717-4 · 3.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract Objective: Vaginal delivery of fetal breech presentation is considered to be a challenge for obstetricians. The purpose of this study was to show that vaginal delivery in all fours position is feasible and safe for mother and child compared with vaginal breech and classic support. Methods: A single-center prospective observational case series of breech delivery (n=41) in all fours position was compared to a retrospective cohort of breech deliveries in the form of a matched-pair analysis. Results: Deliveries in the all fours position successfully took place without obstetric intervention in 70.7% of deliveries (n=29/41), and those including intervention in 90.2% (n=37/41). The rate of maternal perineal injuries was reduced (14.6% vs. 58.5%, P<0.001). Newborns delivered in all fours position had increased prenatal hypoxic stress with a pH of 7.19 [95% confidence interval (CI) 7.16-7.22] vs. a pH of 7.24 (95% CI 7.21-7.27; P=0.016). With n=24 vs. n=16, a higher number of newborns had a pH of <7.20 (P=0.03) and decreased base excess of -7.2 mmol/L (95% CI -8.2-6.2) vs. -4.8 mmol/L (95% CI -5.7-4.0; P<0.001). However, this had no clinical consequences for the newborns (5 min Apgar score <9: n=5 vs. n=4, not significant; transfer rate to neonatal intensive care unit n=7 vs. n=6, not significant). Conclusion: This is the first clinical evaluation of breech delivery in the all fours position. It is a feasible non-interventional obstetric delivery method. It seems to be safe for the fetus with reduced maternal morbidity. Vaginal delivery of fetal breech presentation, even in the all fours position, creates stress for the newborn.
Journal of Perinatal Medicine 09/2014; DOI:10.1515/jpm-2014-0048 · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This is a pictorial report of a rare sequelae after unintended intraoperative rupture of cystic teratoma. A 30-year-old female patient was operated on for a mature cystic teratoma of the right ovary with an unintended intraoperative rupture of the ovarian tumor during the procedure. Postoperatively, the final immune-histologic report showed partial neuroendocrine differentiation of immature origin. At re-laparoscopy for staging 7 weeks later several suspicious peritoneal lesions of up to 2.5 cm diameter were discovered and excised for which malignancy could not be excluded macroscopically. However, final histologic report revealed foreign body reaction related to spilling of content of the mature teratoma. This local peritoneal reaction is not according to the well-known chemical peritonitis. Postoperative follow up regarding symptomatic recurrence was uneventful.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: To compare the fetal outcome of preterm breech infants delivered vaginally (VD) or by cesarean section (CS).
A monocentric, retrospective consecutive case series of preterm breech deliveries between 24-37 gestational weeks over 10 years from 1/2000 to 12/2009 was performed in a perinatal care center (Level 1) at the University Clinic of Salzburg, Austria. Data from hospital database were statistically analyzed and compared regarding birth weight, head circumference, parity, transfer rate to neonatal intensive care unit (NICU), arterial and venous cord blood pH and base excess (BE), arterial cord blood pH ≤ 7.10 and BE ≤ -11. Special focus was on fetal outcome of elective CS preterm breech deliveries with a non-urgent medical indication compared to VD.
Among 22.115 deliveries, there were 346 live-born preterm singletons and twins in breech presentation (1.56 %), born between 24 + 0 and 37 + 0 gestational weeks. 180 CS and 36 vaginally delivered preterm breech infants were statistically evaluated. On comparing CS vs. VD for premature breech singletons, arterial cord blood pH and BE were lower in the VD group. VD twins had a lower arterial cord blood pH than CS twins. All other parameters were comparable. In preterm breech singletons with non-urgent CS, a statistical analysis was not possible due to small numbers. The VD twin group revealed lower values in birth weight, head circumference, arterial cord blood pH and BE, but no significant difference in venous cord blood pH and BE and transfer rate to NICU.
Although general recommendations regarding a superior mode of delivery for improved fetal outcome of preterm breech infants cannot be given, these data do not support a policy of routine CS.
Archives of Gynecology 03/2014; 290(2). DOI:10.1007/s00404-014-3203-y · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess acceptance and impact of external cephalic version (ECV) for breech presentation at term on maternal satisfaction with childbirth.
Retrospective study on n = 131 women with breech presentation comparing maternal satisfaction after ECV and consecutive childbirth (n = 66; 50.4 % of these successful attempts in n = 33; 50 %) against the group without ECV and primary caesarean section (CS) (n = 65; 49.6 %) instead using a questionnaire.
Women with successful ECV tolerated side effects of the intervention better than after unsuccessful ECV (pain, tocolytics, mental and physical state, for all p < 0.001). They were not more satisfied with childbirth than women who experienced an unsuccessful ECV (p = 0.37). However, they would undergo the procedure again (p = 0.003) and would recommend it to other women (p < 0.001). Only women with spontaneous vaginal deliveries after successful version were more satisfied with childbirth than women with planned CS (p = 0.05). Women with version attempts tend to perceive childbirth as being less problematic with fewer complications (9.5 vs. 19 %, p = 0.12). Unsuccessful ECVs had no negative impact on satisfaction with childbirth (p = 0.072).
Attempting ECV seems to be an option for increasing the rate of vaginal births with breech presentation without negative impact on maternal satisfaction regarding consecutive childbirth.
Archives of Gynecology 08/2013; 289(3). DOI:10.1007/s00404-013-3007-5 · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Biomarkers uPA/PAI-1 as recommended by ASCO and AGO are used in primary breast cancer to avoid unnecessary CTX in medium risk-recurrence patients. This study verified how many CTX cycles and CTX-related direct medication costs can be avoided by uPA/PAI-1 testing. A prospective, non-interventional, multi-center study was performed among six Certified Breast Centers to analyze application of uPA/PAI-1 and consecutive decision-making. CTX avoided were identified and direct costs for CTX, CTX-related concomitant medication and febrile neutropenia (FN) prophylaxis with G-CSF calculated. In n = 93 breast cancers n = 35 CTX (37.6%) with 210 CTX cycles were avoided according to uPA/PAI-1 test result. uPA/PAI-1 testing saved direct medication costs for CTX of 177,453 €, CTX-related concomitant medication of 27,482 € and FN prophylaxis of 20,599 €, overall 225,534 €. At test costs at 287.50 € uPA/PAI-1 testing resulted in additional costs of 26,737.50 €. uPA/PAI-1 has proven to be cost-effective at a return-on-investment ratio of 8.4:1. Indirect cost savings further increase this ROI. These results support decision-making for cost-effective diagnostics and therapy in breast cancer.
Breast (Edinburgh, Scotland) 05/2013; 22(4). DOI:10.1016/j.breast.2013.04.009 · 2.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Invasion factors uPA/PAI-1 are guideline-recommended (ASCO, AGO) biomarkers for decision support regarding adjuvant chemotherapy (CTX) in women with primary breast cancer. They define a high-risk group with strong benefit from adjuvant CTX and a low-risk group with uncertain benefit and excellent survival without CTX. In a target population (age > 35/N0/G2/HR+/HER2-), administration of adjuvant CTX is not mandatory in Germany and other countries. Based on existing data, this economic model was developed to determine for the first time health economic impact of uPA/PAI-1 testing. Incremental cost-effectiveness ratio (ICER) resulting from uPA/PAI-1 testing was estimated for the target population by Markov modeling and sensitivity analysis. Survival data, CTX-uPA/PAI-1 interactions, and uPA/PAI-1 hazard ratios were derived from the Chemo N0 trial and other evidence. Incremental costs were computed from a payer's perspective appropriate to the German setting. Incremental effectiveness in life years (ly) was estimated taking into account age-adjusted life expectancy, disease-free survival (with/without CTX), and 2 years post-relapse survival. Sensitivity analysis was performed by varying residual adjuvant CTX benefit in the low-risk group, denoted HR_CTX(LR), in range 0.8-0.99. All patients receive adjuvant endocrine therapy. Test is restricted to patients willing to forgo CTX if both markers are below specific cut-off values and to undergo CTX otherwise. For a typical 55-year-old patient, comparing to an "all-CTX" strategy without the test, ICER (all-CTX vs. test) > 50,000 if HR_CTX(LR) > 0.85, with savings of 18,500 per low-risk patient attributable to the test. The cost-effectiveness of forgoing CTX is very high as HR_CTX(LR) approaches one. Conversely, comparing to a "no-CTX" strategy (e.g., patients who initially refuse CTX) without the test, the test is very cost-effective at all ages in the target group if high-risk patients are willing to undergo CTX: ICER (test vs. no-CTX) < 6,000 at age 55 and even better at younger ages, remaining < 25,000 up to age 75. The main determinants of cost utility are age and residual CTX benefit in low-uPA/PAI-1 patients. The uPA/PAI-1 test is cost-effective in the target group compared to either an "all-CTX" or a "no-CTX" scenario. This model thus lends health economic support to current guideline recommendations that uPA/PAI-1 testing is beneficial for BC patients with no lymph node involvement.
Breast Cancer Research and Treatment 04/2013; 138(3). DOI:10.1007/s10549-013-2496-z · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Breast Care 03/2013; 8(1):7-14. DOI:10.1159/000348370 · 0.63 Impact Factor