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Soluble Fms-like tyrosine kinase-1 (sFlt-1) is thought to be causative in the pathogenesis of preeclampsia (PE) and specific removal of sFlt-1 via dextran sulfate cellulose (DSC)-apheresis was suggested as cure to allow prolongation of pregnancy in preterm PE. However, in addition a deranged lipoprotein metabolism may impact endothelial and placental function in PE. Lipoprotein-apheresis by heparin-mediated extracorporeal LDL-precipitation (H.E.L.P.) was previously applied and has been shown to alleviate symptoms in PE. This clinical trial reevaluates the clinical efficacy of H.E.L.P.-apheresis in PE considering sFlt-1.Open pilot study assessing the prolongation by H.E.L.P.-apheresis in 6 women (30-41 years) with very preterm PE (24+4 to 27+0 gestational weeks (GW)) (NCT01967355) compared to a historic control-group matched for GW at admission (28 GW; n = 6). Clinical outcome of mothers and babies, and pre- and post H.E.L.P.-apheresis levels of sFlt-1 and PlGF were monitored.In apheresis patients (2-6 treatments), average time from admission to birth was 15.0 days (6.3 days in controls; p = 0.027). Lung maturation was induced in all treated cases, and all children were released in healthy condition. Apheresis reduced triglycerides and LDL-cholesterol by more than 40%. Although H.E.L.P.-apheresis induced a transient peak baseline levels did not change and rather stabilized sFlt-1 levels at pre-apheresis levels throughout treatments, with sFlt-1/PLGF ratio remaining unaffected.H.E.L.P.-apheresis proved again to be safe and prolongs pregnancies in PE. However, without changing sFlt-1 levels below baseline lowering lipids or other yet undefined factors appear to be of more relevance than reducing sFlt-1.

Objective Soluble Fms-like tyrosine kinase-1 (sFlt-1) is thought to be causative in the pathogenesis of preeclampsia (PE) and specific removal of sFlt-1 via dextran sulfate cellulose (DSC)-apheresis was suggested as a cure to allow for prolongation of pregnancy in preterm PE. However, in addition a deranged lipoprotein metabolism may impact endothelial and placental function in PE. Lipoprotein-apheresis by heparin-mediated extracorporeal LDL-precipitation (H.E.L.P.) was previously applied and has been shown to alleviate symptoms in PE. This clinical trial reevaluates the clinical efficacy of H.E.L.P.-apheresis in PE considering sFlt-1. Methods Open pilot study assessing the prolongation by H.E.L.P.-apheresis in 6 women (30–41 years) with very preterm PE (24 + 4 to 27 + 0 gestational weeks (GW)) (NCT01967355) compared to a historic control-group matched for GW at admission. Clinical outcome of mothers and babies, and pre- and post H.E.L.P.-apheresis levels of sFlt-1and PlGF were monitored. Results In apheresis patients (2–6 treatments), average time from admission to birth was 15.0 days (6.3 days in controls; p = 0.027). Lung maturation was induced in all treated cases, and all children were released in healthy condition. Apheresis reduced triglycerides and LDL-cholesterol by more than 40%. Although H.E.L.P.-apheresis induced a transient peak, baseline levels did not change and rather stabilized sFlt-1 levels at pre-apheresis levels Discussion Lipoprotein-apheresis proved again to be safe and prolongs pregnancies in PE. However, without changing sFlt-1 levels below baseline lowering lipids or other yet undefined factors appear to be of more relevance than reducing sFlt-1.

Multiple myeloma is the second most commonly diagnosed hematologic malignancy. It is characterized by the accumulation of monoclonal plasma cells. It typically manifests in the sixth decade of life or later, whereas the incidence in patients who are younger than 40 years old is extremely rare. Here, we report the case of a 34-year-old prima gravida, diagnosed with a κ light-chain myeloma (Durie&Salmon stage IIIA, International Staging System I) in the 23rd week of pregnancy. Our multimodal therapeutic approach during pregnancy, the delivery of a healthy male, and initiation of intensive anti-myeloma treatment thereafter (induction with bortezomib, cyclophosphamide, and dexamethasone, followed by tandem autologous peripheral blood stem cell transplantation) are described. Furthermore, we provide a comprehensive review of all 18 cases published between 1965 and 2010 in which a multiple myeloma was diagnosed and treated following different regimes and approaches before, during, or shortly after pregnancy. All delivered newborns were healthy, whereas the mothers' outcomes varied strongly. In our specific case, complete remission was achieved after tandem autologous peripheral blood stem cell transplantation. Emerging from these literature data and our case, we conclude that while awaiting delivery, the application of prednisolone as a nontoxic, but active anti-myeloma therapy can be recommended. Intensified postpartum anti-myeloma therapy should be induced as soon as possible to efficiently reduce myeloma burden and avoid organ damage in these young females.

Introduction Preeclampsia is a potentially life threatening disease occurring in pregnancy. The only causative cure consists in delivery with all the risks for a premature fetus. In preeclampsia, the lipid metabolism is substantially altered and lipid apheresis is being explored as a possible therapeutic approach to prolong preeclamptic pregnancies and allow further maturation of the fetus. In the Freiburg H.E.L.P.-Apheresis Study, 6 early onset preeclamptic patients were treated with H.E.L.P. apheresis. Objective/hypothesis Detailed analysis of apheresis-induced dynamics in serum lipid parameters. Methods 6 early onset preeclamptic patients underwent repeated apheresis treatments (n = 23). We evaluated parameters of the lipoprotein metabolism in 6 preeclamptic patients in detail. Results Reduction of lipoproteins by apheresis was lower than theoretically expected. Lipids reached previous pre-apheresis levels before the next apheresis even though apheresis was repeated within 2.9 ± 1.2 days. Fractional catabolic rates and synthetic rates were found to be substantially elevated, with fractional catabolic rates for ApoB/ LDL-cholesterol being 0.7 ± 0.3/ 0.4 ± 0.2 [day−1] and synthetic rates being 26 ± 8/ 17 ± 8 [mg*kg−1*day−1]. The distribution of LDL-subclasses after apheresis shifted to larger buoyant LDL, while IDL levels remained unaffected. Discussion Apheresis induced changes in lipoprotein profiles point to an underlying remnant removal disease like imbalance in plasma lipid conversion during preeclamptic conditions.

Background Preeclampsia (PE) is a life-threatening complication of pregnancy. To date the only therapy of severe PE consists in timely delivery of the fetus. In PE a deranged lipoprotein metabolism considered to impair endothelial function is observed. Heparin-mediated extracorporeal LDL-precipitation (H.E.L.P.)-apheresis is an established method for lipoprotein removal and has already been successfully applied in PE. Recently, angiogenetic and anti-angiogenetic factors like placenta growth factor (PlGF) and soluble Fms-like tyrosine kinase-1 (sFlt-1) are discussed as risk factors and removal of sFlt-1 by dextran sulfate column (DCS) apheresis is suggested as specific cure for PE. By contrast, H.E.L.P.-apheresis does not remove sFlt-1. The present clinical trial revaluates the clinical efficacy of H.E.L.P.-apheresis in PE with focus on sFlt-1 and PlGF. Methods Open pilot study assessing the prolongation by H.E.L.P.-apheresis in 6 women (30–41 years) with very preterm PE (24 + 4 to 27 + 0 gestational weeks (GW)) (NCT01967355) compared to a historic untreated PE-group matching treated patients by GW at admission ( Results Women with PE received apheresis 2–6 times. In treated patients the average time from admission to birth was 15.0 days compared to 6.3 days in controls (p = 0.027). In treated patients the prolongation of gestation by apheresis converted to a mean fetal weight gain of 101 grams (p = 0.029). Lung maturation could be induced in all treated cases and all children could be dismissed in healthy condition. Apheresis significantly reduced levels of total cholesterol (−33%), triglycerides (−43%), and LDL-cholesterol (−44%). However, sFlt-1 was not reduced but levels significantly increased initially by H.E.L.P.-apheresis and dropped to almost pre-apheresis levels before next apheresis, with sFlt-1/PLGF ratio remaining unaffected. Conclusions H.E.L.P.-apheresis proved again to be a safe therapeutic option to prolong pregnancies in PE and results in significant fetal weight gain. However, H.E.L.P.-apheresis does not reduce circulating sFlt-1 levels. Thus, reducing lipids and other pro-inflammatory factors may be more relevant than reducing circulating sFlt-1 to improve outcome in PE.

The purpose was to evaluate the validity of transvaginal color Doppler sonography for differentiating between benign and malignant ovarian tumors. Color Doppler and Duplex measurements were obtained in 212 (144 benign, 68 malignant) ovarian and tubarian tumors preoperatively. One hundred and thirty-one patients were postmenopausal and 81 premenopausal. An ATL UM9/HDI was used. The following criteria were analyzed: minimum and mean resistance index and pulsatility index, number and distribution of tumor arteries, diastolic notch, and the maximum, minimum, mean, and sum of all peak systolic, maximum enddiastolic, and time-average maximum velocities. Most criteria showed highly significant differences between benign and malignant tumors with variable overlaps. RI min gives a sensitivity of 80%, specificity of 69%, and accuracy of 75% for postmenopausal patients and 80, 59, and 67% for pre- and postmenopausal patients, respectively. PI min gives equivalent results. The number of tumor arteries and the maximum flow velocities increase the accuracy. The summation of all flow velocities gives the best result with a sensitivity of 93%, specificity of 85%, and accuracy of 87% for postmenopausal and 91, 76, and 80% for pre- and postmenopausal tumors, respectively. Flow data show no relevant differences between low malignant potential tumors and ovarian carcinomas. Serous cystadenomas and benign teratomas show higher differences than mucinous cystadenomas, functional cysts, and endometriomas in comparison to malignancies. A separate analysis of pre- and postmenopausal tumors is important. Differentiation seemed better for post- than for premenopausal tumors. The four flow criteria (RI min , number of tumor arteries, and maximum and sum of all peak systolic velocities) seemed appropriate for tumor differentiation. However, this study confirms that a single measurement is not sufficient to differentiate ovarian lesions. Measurements of flow velocities (e.g., maximum and sum of all peak systolic velocities) are superior compared with RI min and PI min .

Color Doppler technique has been available for several years. The sensitivity of the equipment has improved and allows for assessment of tumor vascularity. We investigated multiple parameters in 258 patients, with 176 benign and 82 malignant lesions to define characteristic flow criteria. Median (25-75% quartiles) and p-values are given for benign vs. malignant lesions. Number of tumor vessels: 2 (1-2) vs. 8 (5-14), p0.0001; mean peak systolic flow velocity: 11.1 cm/s (6.4-14.9) vs. 18.8 cm/s (13.7-25.1), p0.0001; maximum flow velocity: 12.5 cm/s (6.7-18) vs. 32.5 cm/s (22.5-47.3), p0.0001; sum of all systolic flow velocities: 18.9 cm/s (7-34.2) vs. 147 cm/s (71.3-266.7), p0.0001; minimum systolic flow velocity: 8.9 cm/s (5.4-12.1) vs. 9 cm/s (6.3-11.3), p0.05; average resistance index (RI): 0.68 (0.58-0.72) vs. 0.75 (0.67-0.81), p0.05; maximum RI: 0.71 (0.65-0.78) vs. 0.88 (0.78-0.99), p0.0001; minimum RI: 0.64 (0.57-0.68) vs. 0.64 (0.53-0.71), p0.05; average A/B ratio: 3.1 (2.7-3.7) vs. 4.3 (3.2-7.7), p0.0001; maximum A/B ratio: 3.4 (2.9-4.6) vs. 8.4 (4.5-9.9), p0.0001; minimum A/B ratio: 2.8 (2.3-3.2) vs. 2.9 (2.2-3.5), p0.05. The data analysis shows that flow resistance in malignancies is increased. This is in contrast to gynecological malignancies, where an increased diastolic flow indicates that flow resistance is decreased.

Objectives Alterations in lipoprotein metabolism have been proposed as a possible pathophysiologic factor for preeclampsia. Elevation of very low density lipoproteins (VLDL) and predominance of atherogenic small dense low density lipoproteins (sdLDL) have been demonstrated in preeclampsia. Heparin-mediated-extracorporeal-LDL-precipitation (H.E.L.P.)-apheresis is an established method for lipoprotein removal and regeneration of endothelial function in severe hyperlipidemia. Wang et al. (2006) successfully used H.E.L.P.-apheresis in a pilot study to prolong preeclamptic pregnancies. We investigated alterations in the lipidprofile and the effects of H.E.L.P.-apheresis in the prolongation of hypertensive pregnancies. Methods Six patients with early pregnancy complicated by hypertension were treated with H.E.L.P.-apheresis. Blood was collected before and after apheresis and subjected to ultracentrifugation for determination of lipid parameters. Results A total of 23 apheresis treatments (2–6 per patient) were performed without severe complications. Within apoB-containing lipoproteins, VLDL (−58%) and sdLDL (L5: −65% and L6: −68%) were removed at highest proportion. Cholesterol was reduced by 32% and triglycerides by 44%. Soluble fms-like tyrosine kinase-1 (sFlt-1) and placenta-growth-factor (PlGF) were not removed by H.E.L.P. Pregnancies continued for 4–14 days and lung maturation was successfully initiated before termination of pregnancy by caesarean section. Conclusions H.E.L.P.-apheresis appears to preferentially address atherogenic lipoproteins, relevant to preeclampsia. Disclosures C. Contini: None. B. Konig: None. F. Markfeld-Erol: None. M. Kunze: None. S. Zschiedrich: None. H. Prompeler: None. G. Putz: None. K. Winkler: Commercial Interest: BBraun Melsungen AG provided the H.E.L.P.-system; Research Support: BBraun Melsungen AG; Speaker: BBraun Melsungen AG.