Diagnosis and treatment of iron-deficiency anaemia during pregnancy and postpartum

Introduction: Iron-deficiency anaemia during pregnancy and postpartum occurs frequently and may lead to severe maternal and foetal complications. New treatment regimens include intravenous iron administration in particular clinical situations. The aim of the study was to determine optimal diagnostic and therapeutic approaches to iron-deficiency anaemia during pregnancy and postpartum. Methods: The evidence from data available from published studies and recommendations regarding diagnosis and treatment were reviewed. As conclusions, recommendations are given by an expert panel. Results: During pregnancy, oral iron therapy is given as first-line treatment. In cases with lack of efficacy, unwarranted side effects or very low haemoglobin values, intravenous iron treatment with iron carboxymaltose is a preferable alternative, although data regarding safety are limited. In the postpartum period, haemoglobin values less than 95g/L are treated ideally by intravenous carboxymaltose, leading to more rapid haemoglobin recovery. Conclusion: New intravenous iron preparations such as iron carboxymaltose have an excellent efficacy, side effect profile and advantages as compared to oral iron preparations for particular clinical indication

Expression of the breast differentiation antigen NY-BR-1 in a phyllodes tumor of the vulva

We describe a phyllodes tumor of borderline malignancy in the labium majus of a 49-year-old woman. The histogenetic origin of phyllodes tumors in the vulva is controversial. Strong immunoreactivity for NY-BR-1, a novel breast differentiation antigen, was demonstrated within the epithelial components of the phyllodes tumor. A similar expression pattern was observed in mammary-like glands of the vulva. These findings provide further evidence that phyllodes tumors of the vulva might derive from mammary-like glands in the labium majus or from ectopic breast tissu

Interpolation of Scientific Image Databases

This paper explores how recent convolutional neural network (CNN)-based techniques can be used to interpolate images inside scientific image databases. These databases are frequently used for the interactive visualization of large-scale simulations, where images correspond to samples of the parameter space (e.g., timesteps, isovalues, thresholds, etc.) and the visualization space (e.g., camera locations, clipping planes, etc.). These databases can be browsed post hoc along the sampling axis to emulate real-time interaction with large-scale datasets. However, the resulting databases are limited to their contained images, i.e., the sampling points. In this paper, we explore how efficiently and accurately CNN-based techniques can derive new images by interpolating database elements. We demonstrate on several real-world examples that the size of databases can be further reduced by dropping samples that can be interpolated post hoc with an acceptable error, which we measure qualitatively and quantitatively

Pathological Processing Techniques and Final Diagnosis of Breast Cancer Sentinel Lymph Nodes

Background: Recommendations for intraoperative and postoperative breast sentinel lymph node (SLN) processing differ widely. Micrometastases and isolated tumor cells (ITC) have recently been proposed as prognostically and therapeutically relevant. We compared 3 SLN protocols with regard to intraoperative and postoperative diagnosis. Materials and Methods: SLN in cohort I (270 patients) were intraoperatively assessed by stereomicroscopy. Intraoperative frozen section (IFS) was used only in stereomicroscopically suspicious SLN. In cohort II (197 patients), all SLN were examined with only 1 IFS. Final SLN workup in cohorts I and II consisted of complete step sectioning with immunohistochemistry. In cohort III (268 patients) 2 or more IFS were performed followed by 3 step sections and immunohistochemistry. Results: pN1 stages were significantly higher in cohorts I and II (33.3% and 34.0% respectively) than in cohort III (24.6%). Intraoperative false negativity for the detection of metastases (pN1) ranged from 54.4% (cohort I) and 35.8% (cohort II) to 21.2% (cohort III). In contrast, ITC were detected significantly more frequently in cohort I (9.3%) and cohort II (14.7%) than in cohort III (1.9%). Conclusions: Higher rates of SLN metastases and ITC in cohort I/II compared to cohort III suggest that IFS may result in tissue loss thus increasing the risk of missing metastases. Sparse IFS but complete postoperative SLN workup with step sectioning and immunohistochemistry provides more accurate information regarding minimal disease in SLN, but often results in delayed axillary lymph node dissection. This is important for preoperative patient information and recommendations in SLN processing protocol

«Sister Mary Joseph’s nodule»

Der «Sister Mary Joseph’s nodule» (SMJN) ist ein umbilikaler Knoten, der als Hautmetastase eines intraabdominalen oder pelvinen Karzinoms auftreten kann. Er wurde 1928 erstmalig durch den amerikanischen Chirurgen, Dr. W. J. Mayo (1861–1939), beschrieben. Namensgeberin war seine Operationsassistentin Sister Mary Joseph Dempsey, die ihn auf die umbilikale Veränderung aufmerksam machte [1]. Meist tritt die Metastase im Spätstadium der zugrunde liegenden Tumorerkrankung auf. Sie kann sich allerdings auch als erstes klinisch fassbares Symptom manifestieren

Monitoring activated clotting time for combined heparin and aprotinin application: in vivo evaluation of a new aprotinin-insensitive test using Sonoclot

Objective: Kaolin-based activated clotting time assessed by HEMOCHRON (HkACT) is a clinical standard for heparin monitoring alone and combined with aprotinin during cardiopulmonary bypass (CPB). However, aprotinin is known to prolong not only celite-based but also kaolin-based activated clotting time. Overestimation of activated clotting times implies a potential hazardous risk of subtherapeutic heparin anticoagulation. Recently, a novel ‘aprotinin-insensitive' activated clotting time test has been developed for the SONOCLOT analyzer (SaiACT). The aim of our study was to evaluate SaiACT in patients undergoing CPB in presence of heparin and aprotinin. Methods: Blood samples were taken from 44 elective cardiac surgery patients at the following measurement time points: baseline (T0); before CPB after heparinization (T1 and T2); on CPB, before administration of aprotinin (T3); 15, 30, and 60min on CPB after administration of aprotinin (T4, T5, and T6); after protamine infusion (T7). On each measurement time point, activated clotting time was assessed with HkACT and SaiACT, both in duplicate. Furthermore, the rate of factor Xa inhibition and antithrombin concentration were measured. Statistical analysis was done using Bland and Altman analysis, Pearson's correlation, and ANOVA with post hoc Bonferroni-Dunn correction. Results: Monitoring anticoagulation with SaiACT showed reliable readings. Compared to the established HkACT, SaiACT values were lower at all measurement time points. On CPB but before administration of aprotinin (T3), SaiACT values (mean±SD) were 44±118s lower compared to HkACT. However, the difference between the two measurement techniques increased significantly on CPB after aprotinin administration (T4-T6; 89±152s, P=0.032). Correlation of ACT measurements with anti-Xa activity was unchanged for SaiACT before and after aprotinin administration (r2=0.473 and 0.487, respectively; P=0.794), but was lower for HkACT after aprotinin administration (r2=0.481 and 0.361, respectively; P=0.041). On CPB after administration of aprotinin, 96% of all ACT values were classified as therapeutic by HkACT, but only 86% of all values were classified therapeutic if ACT was determined by SaiACT. Test variability was comparable for SaiACT and HkACT. Conclusions: The use of SaiACT may result in more consistent heparin management that is less affected by aprotinin and a corresponding increase in heparin administration for patients receiving aprotini

Stabilization and humanization of a single-chain Fv antibody fragment specific for human lymphocyte antigen CD19 by designed point mutations and CDR-grafting onto a human framework

A single-chain Fv (scFv) fragment derived from the murine antibody 4G7, specific for human lymphocyte CD19, was engineered for stability and expression in Escherichia coli in view of future use as a therapeutic protein. We compared two orthogonal knowledge-based procedures. In one approach, we designed a mutant with 14 single amino-acid substitutions predicted to correct destabilizing residues in the 4G7-wt sequence to create 4G7-mut. In the second variant, the murine CDRs were grafted to the human acceptor framework huVκ3-huVH3, with 11 additional point mutations introduced to obtain a better match between CDR graft and acceptor framework, to arrive at 4G7-graft. Compared to 4G7-wt, 4G7-mut showed greater thermodynamic stability in guanidinium chloride-induced equilibrium denaturation experiments and somewhat greater stability in human serum. The loop graft maintained the comparatively high stability of the murine loop donor, but did not improve it further. Our analysis indicates that this is due to subtle strain introduced between CDRs and framework, mitigating the otherwise highly favorable properties of the human acceptor framework. This slight strain in the loop graft is also reflected in the binding affinities for CD19 on leukemic cells of 8.4 nM for 4G7-wt, 16.4 nM for 4G7-mut and 30.0 nM for 4G7-graft. This comparison of knowledge-based mutation and loop-grafting-based approaches will be important, when moving molecules forward to therapeutic application

Pegfilgrastim reduces the length of hospitalization and the time to engraftment in multiple myeloma patients treated with melphalan 200 and auto-SCT compared with filgrastim

To reduce the duration of neutropenia after conditioning chemotherapy and autologous peripheral blood stem cell transplantation (APBSCT), granulocyte-colony stimulating factors (G-CSF) are commonly administered. We retrospectively evaluated the impact of pegfilgrastim compared to filgrastim on neutrophil engraftment, hospital stay, and supportive measures in patients with multiple myeloma after conditioning with Melphalan 200 (Mel200) followed by APBSCT. Ninety-two APBSCT after Mel200 treatment were performed in 72 patients between January 2006 and December 2009 at our institution. Patients received either single-dose pegfilgrastim (n = 46; 50%), or daily filgrastim (n = 46; 50%) after APBSCT (median duration of filgrastim use, 9days; range, 3-14days). Duration of neutropenia grade IV was shorter with pegfilgrastim compared with filgrastim (median, 5days (range, 3-14days) versus 6days (range, 3-9days), p = 0.0079). The length of hospitalization differed significantly (pegfilgrastim (median, 14.5days; range, 11-47days) versus filgrastim (median, 15.5days; range, 12-64days), p = 0.024). Pegfilgrastim-treated patients had less red blood cell transfusions (median, 0 transfusions (range, 0-10) versus 0.5 transfusions (range, 0-9), p = 0.00065). Pegfilgrastim was associated with reduced cost of the treatment procedure compared with filgrastim (p = 0.031). Pegfilgrastim appears to be at least equivalent to filgrastim without additional expenditure in myeloma patients treated with Mel200 and APBSC

Discovery of long-distance gamete dispersal in a lichen-forming ascomycete

Accurate estimates of gamete and offspring dispersal range are required for the understanding and prediction of spatial population dynamics and species persistence. Little is known about gamete dispersal in fungi, especially in lichen-forming ascomycetes. Here, we estimate the dispersal functions of clonal propagules, gametes and ascospores of the epiphytic lichen Lobaria pulmonaria. We use hierarchical Bayesian parentage analysis, which integrates genetic and ecological information from multiannual colonization and dispersal source data collected in a large, oldgrowth forest landscape. The effective dispersal range of gametes is several hundred metres to kilometres from potential paternal individuals. By contrast, clonal propagules disperse only tens of metres, and ascospores disperse over several thousand metres. Our study reveals the dispersal distances of individual reproductive units; clonal propagules, gametes and ascospores, which is of great importance for a thorough understanding of the spatial dynamics of ascomycetes. Sexual reproduction occurs between distant individuals. However, whereas gametes and ascospores disperse over long distances, the overall rate of colonization of trees is low. Hence, establishment is the limiting factor for the colonization of new host trees by the lichen in old- growth landscapes.Peer reviewe