Delivery of the second twin: influence of presentation on neonatal outcome, a case controlled study.

BACKGROUND: Spontaneous vaginal twin delivery after 32nd week of gestation is safe when first twin presenting cephalic. Aim of this study is to identify obstetric factors influencing the condition of second twin and to verify whether non-cephalic presentation and vaginal breech delivery of the second twin is safe. METHODS: This is a retrospective case controlled cohort study of 717 uncomplicated twin deliveries ≥32 + 0 weeks of gestation from 2005 to 2014 in two tertiary perinatal centers. Obstetric parameters were evaluated in three groups with descriptive, univariate logistic regression analysis for perinatal outcome of second twins. RESULTS: The three groups included twins delivered by elective cesarean section ECS (n = 277, 38.6%), by unplanned cesarean section UPC (n = 233, 32.5%) and vaginally (n = 207, 28.9%). Serious adverse fetal outcome is rare and we found no differences between the groups. Second twins after ECS had significant better umbilical artery UA pH (p < 0.001) and better Apgar compared to UPC (p = 0.002). Variables for a fetal population "at risk" for adverse neonatal outcome after vaginal delivery (UA pH < 7.20, Apgar 5´ < 9) were associated with higher gestational age (p = 0.001), longer twin-twin interval (p = 0.05) and vacuum extraction of twin A (p = 0.04). Non-cephalic presentation of second twins was not associated (UA pH < 7.20 OR 1.97, CI 95% 0.93-4.22, p = 0.07, Apgar 5´ < 9 OR 1.63, CI 95% 0.70-3.77, p = 0.25, Transfer to neonatal intermediate care unit p = 0.48). Twenty-one second twins (2,9%) were delivered by cesarean section following vaginal delivery of the first twin. Even though non-cephalic presentation was overrepresented in this subgroup, outcome variables were not significantly different compared to cephalic presentation. CONCLUSIONS: Even though elective cesarean means reduced stress for second twins this seems not to be clinically relevant. Non-cephalic presentation of the second twin does not significantly influence the perinatal outcome of the second twin but might be a risk factor for vaginal-cesarean birth.

Mesonephric adenocarcinoma of the vagina : Diagnosis and multimodal treatment of a rare tumor and analysis of worldwide experience.

BACKGROUND: Mesonephric adenocarcinoma of the vagina is an extremely rare tumor of the female genital tract, with only a few cases reported so far worldwide. Consequently, there is no established standard treatment and limited knowledge about the prognosis and biologic behavior of vaginal mesonephric adenocarcinoma. METHODS: This report documents a new case of vaginal mesonephric adenocarcinoma diagnosed in a 54-year-old woman, and analyzes this in the context of all previously published cases. RESULTS: MRI demonstrated that the 2.5 × 1.8 cm tumor of the vaginal wall was invading urethra and bladder. Following surgical excision, histologic analysis determined mesonephric adenocarcinoma of the vagina, stage pT2 R1. In order to avoid the mutilating extended surgery which would be required to reach R0 and considerable impairment of quality of life, adjuvant radiochemotherapy was administered with external radiation and brachytherapy, including 5 cycles of cisplatin (40 mg/m²) for radiosensitization. After 4 years of continuous oncologic follow-up, the patient is alive and clinically free of disease. CONCLUSION: In this case it was shown that adjuvant radiochemotherapy with radiation and brachytherapy was effective to manage the surgical R1 situation and maintain the patient's life quality. More published cases reports are needed to gradually substantiate optimal treatment strategies.

Mechanical fibrinogen-depletion supports heparin-free mesenchymal stem cell propagation in human platelet lysate.

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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Breech delivery in the all fours position: a prospective observational comparative study with classic assistance.

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.

Local foreign body reaction of peritoneum after rupture of cystic partially immature teratoma.

This is a pictorial report of rare sequelae after an unintended intraoperative rupture of a cystic teratoma. A 30-year-old woman 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 an immature origin. At relaparoscopy for staging 7 weeks later, several suspicious peritoneal lesions of up to a 2.5-cm diameter were discovered and excised for which malignancy could not be excluded macroscopically. However, the final histologic report revealed a foreign body reaction related to spilling of the content of the mature teratoma. It is important to distinguish local peritoneal reaction from chemical peritonitis. The postoperative follow-up regarding symptomatic recurrence was uneventful.

Comparison of fetal outcome in premature vaginal or cesarean breech delivery at 24-37 gestational weeks.

PURPOSE: To compare the fetal outcome of preterm breech infants delivered vaginally (VD) or by cesarean section (CS). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Health economic impact of risk group selection according to ASCO-recommended biomarkers uPA/PAI-1 in node-negative primary breast cancer.

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.

AAGL Practice Report: Practice Guidelines for the Management of Hysteroscopic Distending Media: (Replaces Hysteroscopic Fluid Monitoring Guidelines. J Am Assoc Gynecol Laparosc. 2000;7:167-168.).

The objective of this guideline is to provide clinicians with evidence-based information about commonly used and available hysteroscopic distending media to guide them in their performance of both diagnostic and operative hysteroscopy. While necessary for the performance of hysteroscopy and hysteroscopically-directed procedures, distending media, if absorbed systemically in sufficient amounts, can have associated adverse events, including life-threatening complications. Consequently, understanding the physical properties and the potential risks associated with the use of the various distending media is critical for the safe performance of hysteroscopic procedures. This report was developed under the direction of the Practice Committee of the AAGL as a service to their members and other practicing clinicians.

A pragmatic guide on how physicians can take over financial control of their clinical practice.

Control of clinical cost is becoming increasingly important in health care worldwide. Physicians should accept the limitation of resources and take responsibility to improve their clinical cost-reimbursement ratio. To achieve this, they will need basic education in clinic management to control and adjust costs and reimbursement, without impacting professional quality of care. Rational use of diagnostics and therapy should be implemented and frequently verified. Physicians are the only professionals that are able to integrate economics with health care. This is in the best interest of patients and will improve a physician's position, influence, and professional freedom levels within our hospitals.

Novel markers of mesenchymal stem cells defined by genome-wide gene expression analysis of stromal cells from different sources.

Mesenchymal stem cells (MSC) represent a mixture of different cell types, of which only a minority is therapeutically relevant. Surface markers specifically identifying non-differentiated MSC from their differentiated progeny have not been described in sufficient detail. We here compare the gene expression profile of the in vivo bone-forming bone marrow-derived MSC (BM-MSC) with non-bone-forming umbilical vein stromal cells (UVSC) and other non-MSC. Clustering analysis shows that UVSC are a lineage homogeneous cell population, clearly distinct from MSC, other mesenchymal lineages and hematopoietic cells. We find that 89 transcripts of membrane-associated proteins are represented more in cultured BM-MSC than in UVSC. These include previously identified molecules, but also novel markers like NOTCH3, JAG1, and ITGA11. We show that the latter three molecules are also expressed on fibroblast colony-forming units (CFU-F). Both NOTCH3 and ITGA11, but not JAG1, further enrich for CFU-F when combined with CD146, a known marker of cells with MSC activity in vivo. Differentiation studies show that NOTCH3+ and CD146+ NOTCH3+ cells sorted from cultured BM-MSC are capable of adipogenic and osteogenic progeny, while ITGA11-expressing cells mainly show an osteogenic differentiation profile with limited adipogenic differentiation. Our observations may facilitate the study of lineage relationships in MSC as well as facilitate the development of more homogeneous cell populations for mesenchymal cell therapy.

Comparison of actual hospital costs versus DRG revenues for in-patient treatment of febrile neutropenia during adjuvant anthracycline plus/minus taxane-based chemotherapy for primary breast cancer.

BACKGROUND: In flat-rate reimbursement systems, the hospital's own costs should not exceed its revenues. In a cohort of primary breast cancer (pBC) patients, costs and reimbursement for febrile neutropenia (FN) were compared to verify cost coverage. METHODS: A prospective, observational study in pBC patients receiving adjuvant anthracycline ± taxane-based chemotherapy calculated the costs per in-patient FN episode. The correlating revenues were retrospectively analyzed from diagnosis-related group (DRG) invoices. The actual costs of the therapies were compared to the individual DRG revenues, and the results are presented from the provider's perspective. RESULTS: In 50 patients, n = 11 patients were treated for FN as in-patients. The hospital's overall treatment costs were € 18,288, on average (Ø) € 1663 per case (range € 1139-2344); the overall DRG revenues were € 23,593, Ø € 2145 per case (range € 1266-2660). In n = 8 cases, the DRGs were cost covering, and in n = 3 cases, a loss was observed, but overall resulting in a gain of Ø € 482 per case and thus being cost covering for the provider. Inadequate DRG coding (n = 4/11; 36.4%) resulted in a preventable loss of Ø € 1069/case. CONCLUSIONS: The costs of FN treatment vary substantially and DRG reimbursements do not necessarily reflect the provider's costs. Surprisingly, the in-patient treatment of FN here is overall more than cost covering if adequately coded. The main reasons are asymmetrical costs for this FN low-risk pBC group. These results emphasize the importance of correct medical coding to avoid potential losses.

Management of febrile neutropenia--a German prospective hospital cost analysis in lymphoproliferative disorders, non-small cell lung cancer, and primary breast cancer.

BACKGROUND: Febrile neutropenia/leukopenia (FN/FL) is the most frequent dose-limiting toxicity of myelosuppressive chemotherapy, but German data on economic consequences are limited. PATIENTS AND METHODS: A prospective, multicentre, longitudinal, observational study was carried out to evaluate the occurrence of FN/FL and its impact on health resource utilization and costs in non-small cell lung cancer (NSCLC), lymphoproliferative disorder (LPD), and primary breast cancer (PBC) patients. Costs are presented from a hospital perspective. RESULTS: A total of 325 consecutive patients (47% LPD, 37% NSCLC, 16% PBC; 46% women; 38% age = 65 years) with 68 FN/FL episodes were evaluated. FN/FL occurred in 22% of the LPD patients, 8% of the NSCLC patients, and 27% of the PBC patients. 55 FN/FL episodes were associated with at least 1 hospital stay (LPD n = 34, NSCLC n = 10, PBC n = 11). Mean (median) cost per FN/FL episode requiring hospital care amounted to € 3,950 (€ 2,355) and varied between € 4,808 (€ 3,056) for LPD, € 3,627 (€ 2,255) for NSCLC, and € 1,827 (€ 1,969) for PBC patients. 12 FN/FL episodes (LPD n = 9, NSCLC n = 3) accounted for 60% of the total expenses. Main cost drivers were hospitalization and drugs (60 and 19% of the total costs). CONCLUSIONS: FN/FL treatment has economic relevance for hospitals. Costs vary between tumour types, being significantly higher for LPD compared to PBC patients. The impact of clinical characteristics on asymmetrically distributed costs needs further evaluation.

Non-invasive tracking of human haemopoietic CD34(+) stem cells in vivo in immunodeficient mice by using magnetic resonance imaging.

OBJECTIVE: To assess migration of CD34(+) human stem cells to the bone marrow of athymic mice by using magnetic resonance (MR) imaging and Resovist, a contrast agent containing superparamagnetic iron oxide (SPIO) particles. METHODS: All animal and human procedures were approved by our institution's ethics committee, and women had given consent to donate umbilical cord blood (UCB). Balb/c-AnN Foxn1(nu)/Crl mice received intravenous injection of 1 x 10(6) (n=3), 5 x 10(6) (n=3) or 1 x 10(7) (n=3) human Resovist-labelled CD34(+) cells; control mice received Resovist (n=3). MR imaging was performed before, 2 and 24 h after transplantation. Signal intensities of liver, muscle and bone marrow were measured and analysed by ANOVA and post hoc Student's t tests. MR imaging data were verified by histological and immunological detection of both human cell surface markers and carboxydextrancoating of the contrast agent. RESULTS: CD34(+) cells were efficiently labelled by Resovist without impairment of functionality. Twenty-four hours after administration of labelled cells, MR imaging revealed a significant signal decline in the bone marrow, and histological and immunological analyses confirmed the presence of transplanted human CD34(+) cells. CONCLUSION: Intravenously administered Resovist-labelled CD34(+) cells home to bone marrow of mice. Homing can be tracked in vivo by using clinical 1.5-T MR imaging technology.

Chief medical clinic manager of a university OB/GYN clinic--an innovative job description as management response for increase of profitability, quality of care, and physicians' freedom of action.

Leadership structures in German clinics are adjusting parallel to DRG (diagnose-related groups)-induced economic reorientation of the health care system. A Chief Medical Clinic Manager (CMCM) is a new job description and an innovative approach to combine medical competence and business economics at the operational level of care. The ideal qualification is a medical specialist in the clinical field with practical experience in patient care and leadership as well as in hospital economics and quality control. A CMCM is placed at a superior level in the clinic, with authorizing competence for the entire physician team. Main tasks are cost transparency within the clinic, organizational development by structured processes, and financial and strategic controlling of all business aspects. A CMCM induces change management and financial adjustment of care to reimbursement with maintaining the standard of care. In cooperation with the director of the clinic, a CMCM develops a vision for clinic development, an investment strategy, and a business plan. The success parameters are positive operative results of the clinic, cost-covering care, increased investment rate, employee satisfaction, and implementation of innovations in research and therapy. A CMCM thereby increases financial and organizational freedom of action at the clinic level in a non-profit public health care system.

Underfinancing of 90.3% for implant costs of prostheses and expanders in DRG revenues for uni- and bilateral mastectomy with immediate breast reconstruction.

BACKGROUND: From the clinic's point of view economic patient care requires comparison and adjustment of costs to revenues. To verify cost coverage for implants in mastectomy with immediate breast reconstruction, a comprehensive cost-reimbursement analysis was performed. METHODS: Retrospective analysis of the German diagnosis-related group (G-DRG) revenues for implants from the DRG Browser 2007/2009HA and comparison with actual costs for implants in 2009 from the annual clinic report and the database of the controlling department. Calculation of the relative cost coverage for implants in unilateral (DRG J06Z) and bilateral mastectomy (DRG J16Z). RESULTS: In 2009, n = 98 J06Z and n = 18 J16Z were performed. DRG-calculated expenses for implants were € 69.65 for J06Z and € 123.07 for J16Z, i.e. a total of € 9,040.96. Actual costs for all implants were € 121,645.60, mean € 699.11 (€ 404.94-1,171.44). Attributable implant costs for 100% immediate breast reconstruction rate were € 93,679.28. Thus, implants are not cost covering by -90.3% (-82.8 to -94.7%). Subsidies for implants from the clinic's budget range from € 335.29 to € 2,219.81 per case. CONCLUSIONS: Immediate breast reconstruction with implants after mastectomy is - even 6 years after introduction of the DRGs - not adequately calculated to be cost covering since the actual implant costs exceed the calculated revenues by far. At present, these implants are subsidized by the clinic at, on average, 90.3%. If economic patient care is mandatory, a maximum of only 1 in 10 patients with mastectomy can be offered immediate breast reconstruction with implants in Germany.

Primary metastatic leiomyosarcoma of the fallopian tube: a rare case report.

BACKGROUND: Leiomyosarcoma of the fallopian tube is an extremely unusual gynecologic neoplasm. Since 1886, only 19 of about 35 sarcomas of the fallopian tube have been identified as leiomyosarcomas. As such, clinical diagnosis and therapy management are difficult. CASE REPORT: We report on the case of a 59-year-old woman with leiomyosarcoma of the fallopian tube and liver metastases at the time of diagnosis. After initial tumor debulking, she received palliative chemotherapy with gemcitabine 900 mg/m(2) (d1+8) and docetaxel 100 mg/m(2) (d8) (q21). For additional bone metastases, she started local radiation plus bisphosphonates (q28). After 2 cycles of chemotherapy, the disease progressed, and the patient died within 8 months of diagnosis. A review of the literature is given. CONCLUSIONS: Primary metastatic leiomyosarcoma of the fallopian tube is a progressive disease with limited therapy options. For better prognostic evaluation and disease management in such rare cases, it is important to report and compare more cases regarding course of disease and outcome.

Subcutaneous mastectomy with conservation of the nipple-areola skin: broadening the indications.

BACKGROUND: Numerous authors take multiple predictive factors into account to decide whether or not the nipple-areola complex (NAC) can be conserved during mastectomy. These factors include the tumor-nipple distance, tumor size, axillary lymph node status, and lymphovascular invasion. Thus only a very limited percentage of patients can keep their NAC. If the breast gland tissue and all milk ducts can be separated completely from the nipple-areola skin (NA-skin) during subcutaneous mastectomy (SCM), conservation of the NA-skin is feasible even in the case of large, central, and retroareolar tumors. PATIENTS AND METHODS: From July 2003 to May 2006, we performed 109 SCMs on 96 patients. Total mastectomy was indicated in 94 of these breasts, in 16 because of extensive ductal carcinoma in situ, and 78 breasts with invasive carcinoma required additional axillary dissection resulting in indication for modified radical mastectomy. At least 33 of the breasts had malignancy underneath the skin within the areolar margin (centrally located tumors). After dissection of all the breast tissue, the skin envelope with the areola is turned inside out and all milk ducts and any tissue beneath the areola are precisely dissected under the surgeon's visual control. Frozen sections and HE histopathologic examination of this retroareolar tissue next to the skin are requested to decide whether the NA-skin can be preserved or not. This study was registered on the www.clinicaltrials.com website and has the following identification number ID: NCT00641628. RESULTS: We found it necessary to dissect the NA-skin in 13 of 109 breasts (12%), altering the procedure to a skin sparing mastectomy. Necrosis of the NA-skin requiring surgical intervention occurred in only 1 of the conserved 96 breasts. After follow-up of 20 to 54 months (median: 34 months), no recurrence within the nipple-areola region was observed. One local recurrence on the chest wall and 1 axillary recurrence were detected. Of 96 patients, 2 developed distant metastases. One death was recorded. Occasionally, partial necrosis of the nipple occurred, with residual depigmentation of the skin but a good or excellent cosmetic result was maintained in most cases. CONCLUSION: SCM with NAC-skin conservation may be performed according to total mastectomy indications if an intraoperative frozen section (and the corresponding HE histopathology) of the tissue next to the nipple-areola skin is free of tumor. The remaining contraindications for SCM are: extensive tumor involvement of the skin, inflammatory breast cancer, and a clinically suspicious nipple.

Oncostatin M-mediated regulation of KIT-ligand-induced extracellular signal-regulated kinase signaling maintains hematopoietic repopulating activity of Lin-CD34+CD133+ cord blood cells.

We investigated whether KIT signaling was sufficient to maintain human hematopoietic stem cells in culture or whether, as with murine stem cells, signaling through glycoprotein 130 (gp130) is additionally required. Sorted CD34(+)CD133(+)(CD33/CD38/CD71)(-) cells from human umbilical cord blood (UCB) were cultured in the presence of combinations of KIT-ligand (KL) and the gp130 stimulating molecule oncostatin M (OSM). We found that OSM increased KL-induced proliferation, which was accompanied by an expansion in numbers of mature progenitors colony-forming cells (CFC, CAFCw2). More primitive progenitors, CAFCw6 and long-term culture-CFC, were not maintained by KL as a single factor. Although addition of OSM did not improve survival, the KL/OSM combination showed improved maintenance of immature progenitors as well as higher CD34 expression. Similarly, both KL and OSM were required to maintain NOD/SCID-repopulating activity. In experiments to investigate the underlying mechanism, we found that extracellular signal-regulated kinase (ERK) and its downstream target p90 ribosomal S6 kinase were activated by KL and downregulated by the inclusion of OSM during stimulation. The p38 mitogen-activated protein kinase (p38 MAPK) was not modulated by either KL or OSM. Indeed, many of the effects of OSM (increased cell division, maintenance of CFC, and maintenance of high CD34 expression) could be mimicked by using the mitogen-activated protein kinase kinase inhibitor U0126. More importantly, NOD/SCID-repopulating activity was preserved in the KL/U0126-stimulated cells, but not in cells stimulated with a combination of KL and the p38 MAPK inhibitor SB203580. Our results show that the loss of repopulating activity during KL stimulation is counteracted by OSM through the downregulation of ERK pathway signaling. Disclosure of potential conflicts of interest is found at the end of this article.

In vivo osteoprogenitor potency of human stromal cells from different tissues does not correlate with expression of POU5F1 or its pseudogenes.

Expression of "stemness" markers is widely used as a predictor of stem cell properties of mesenchymal stem cells (MSC). Here, we show that bone marrow-derived (BM)-MSC show stem cell-like behavior in vivo; that is, they form ossicles with formation of bone, formation of adipocytes, and establishment of the murine hematopoietic microenvironment. Multipotent umbilical vein-derived stromal cells (UVSC), on the other hand, do not form bone, nor do they give rise to adipocytes in vivo. Despite these differences in stem-cell-like behavior, BM-MSC and UVSC express the two transcripts variants of POU5F1 at a similar level. Also, we found that in BM-MSC and UVSC, POU5F1 is detectable. However, more than 89% of the POU5F1 transcripts correspond to the POU5F1P1, -P3, or -P4 pseudogene. Despite low-level expression of POU5F1, we were unable to precipitate POU5F1 protein in either BM-MSC or UVSC. These results demonstrate that MSC stemness does not correlate to expression of POU5F1 transcripts or its pseudogenes.

Making or losing money with participation in clinical trials: a decision analysis.

BACKGROUND: There is increasing demand and quality-driven pressure from professional organizations for physicians and health care providers to increase participation in clinical studies. But this can have a severe financial impact on the institution, so costs should be identified and calculated in advance. METHOD: In a diagram, the decision-making process to participate in clinical trials based on economic and budget impact is reviewed and analyzed in detail. RESULTS: This flow chart describes how cost-effective participation in clinical trials is determined. Since its implementation, all trials in our institution have been cost covering. CONCLUSIONS: All service and care required within the studies must be distinguished as either medically necessary or study related. Costs for the first category have to be covered by the health care system, but in case of the second category by the study sponsor. The institution's own costs for study-related services should be known and deducted from the study income to determine the actual study gains. Subsidizing studies from tight clinic budgets is difficult in times of rationed medicine and should be avoided. Non-cost-covering clinical studies should be re-negotiated with the sponsor until cost effectiveness is reached. Otherwise, a rejection of study participation for financial reasons should be seriously considered. The design of cost-covering clinical trials supports better recruitment for studies.