Mid-trimester preterm premature rupture of membranes (PPROM), defined as rupture of fetal membranes prior to 28 weeks of gestation, complicates approximately 0.4%-0.7% of all pregnancies. This condition is associated with a very high neonatal mortality rate as well as an increased risk of long-and short-term severe neonatal morbidity. The causes of the mid-trimester PPROM are multifactorial. Altered membrane morphology including marked swelling and disruption of the collagen network which is seen with PPROM can be triggered by bacterial products or/and pro-inflammatory cytokines. Activation of matrix metalloproteinases (MMP) have been implicated in the mechanism of PPROM. The propagation of bacteria is an important contributing factor not only in PPROM, but also in adverse neonatal and maternal outcomes after PPROM. Inflammatory mediators likely play a causative role in both disruption of fetal membrane integrity and activation of uterine contraction. The "classic PPROM" with oligo/anhydramnion is associated with a short latency period and worse neonatal outcome compared to similar gestational aged neonates delivered without antecedent PPROM. The "high PPROM" syndrome is defined as a defect of the chorio-amniotic membranes, which is not located over the internal cervical os. It may be associated with either a normal or reduced amount of amniotic fluid. It may explain why sensitive biochemical tests such as the Amniosure (PAMG-1) or IGFBP-1/alpha fetoprotein test can have a positive result without other signs of overt ROM such as fluid leakage with Valsalva. The membrane defect following fetoscopy also fulfils the criteria for "high PPROM" syndrome. In some cases, the rupture of only one membrane -either the chorionic or amniotic membrane, resulting in "pre-PPROM" could precede "classic PPROM" or "high PPROM". The diagnosis of PPROM is classically established by identification of nitrazine positive, fern positive watery leakage from the cervical canal observed during in specula investigation. Other more recent diagnostic tests include the vaginal swab assay for placental alpha macroglobulin-1 test or AFP and IGFBP1. In some rare cases amniocentesis and infusion of indigo carmine has been used to confirm the diagnosis of PPROM. The management of the PPROM requires balancing the potential neonatal benefits from prolongation of the pregnancy with the risk of intraamniotic infection and its consequences for the mother and infant. Close monitoring for signs of chorioamnionitis (e.g. body temperature, CTG, CRP, leucocytes, IL-6, procalcitonine, amniotic fluid examinations) is necessary to minimize the risk of neonatal and maternal complications. In addition to delayed delivery, broad spectrum antibiotics of penicillin or cephalosporin group and/or macrolide and corticosteroids have been show to improve neonatal outcome [reducing risk of chorioamnionitis (average risk ratio (RR) = 0.66), neonatal infections (RR = 0.67) and abnormal ultrasound scan of neonatal brain (RR = 0.67)]. The positive effect of continuo...

BackgroundBreast cancer tumors are known to be highly heterogeneous and differences in their metabolic phenotypes, especially at protein level, are less well-understood. Profiling of metabolism-related proteins harbors the potential to establish new patient stratification regimes and biomarkers promoting individualized therapy. In our study, we aimed to examine the relationship between metabolism-associated protein expression profiles and clinicopathological characteristics in a large cohort of breast cancer patients.MethodsBreast cancer specimens from 801 consecutive patients, diagnosed between 2009 and 2011, were investigated using reverse phase protein arrays (RPPA). Patients were treated in accordance with national guidelines in five certified German breast centers. To obtain quantitative expression data, 37 antibodies detecting proteins relevant to cancer metabolism, were applied. Hierarchical cluster analysis and individual target characterization were performed. Clustering results and individual protein expression patterns were associated with clinical data. The Kaplan-Meier method was used to estimate survival functions. Univariate and multivariate Cox regression models were applied to assess the impact of protein expression and other clinicopathological features on survival.ResultsWe identified three metabolic clusters of breast cancer, which do not reflect the receptor-defined subtypes, but are significantly correlated with overall survival (OS, p ≤ 0.03) and recurrence-free survival (RFS, p ≤ 0.01). Furthermore, univariate and multivariate analysis of individual protein expression profiles demonstrated the central role of serine hydroxymethyltransferase 2 (SHMT2) and amino acid transporter ASCT2 (SLC1A5) as independent prognostic factors in breast cancer patients. High SHMT2 protein expression was significantly correlated with poor OS (hazard ratio (HR) = 1.53, 95% confidence interval (CI) = 1.10–2.12, p ≤ 0.01) and RFS (HR = 1.54, 95% CI = 1.16–2.04, p ≤ 0.01). High protein expression of ASCT2 was significantly correlated with poor RFS (HR = 1.31, 95% CI = 1.01–1.71, p ≤ 0.05).ConclusionsOur data confirm the heterogeneity of breast tumors at a functional proteomic level and dissects the relationship between metabolism-related proteins, pathological features and patient survival. These observations highlight the importance of SHMT2 and ASCT2 as valuable individual prognostic markers and potential targets for personalized breast cancer therapy.Trial registrationClinicalTrials.gov, NCT01592825. Registered on 3 May 2012.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-017-0905-7) contains supplementary material, which is available to authorized users.

The aim of this study was the realisation and clinical application of MR-guided vacuum biopsy for percutaneous excisional and incisional biopsy of enhancing breast lesions. A breast biopsy system and procedure have been developed which allow precise and safe access to breast lesions in any location and use of vacuum biopsy (VB) under MR guidance. Fifty-one patients with 55 MR-detected lesions were examined. Verification of these diagnoses included re-excision histology of all 14 malignancies and for benign lesions retrospective correlation of histology and imaging, assessment of complete or partial removal of the enhancing area directly after VB (40 of 40 lesions) and follow-up MRI (33 of 40 lesions), which in contrast to conventional needle biopsy can be used as proof of representative removal. Fifty-four of 55 procedures (including 15 lesions

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The purpose of our study was the assessment of the diagnostic value of vacuum core biopsy, which promises high accuracy by minimally invasive percutaneous excision of 1-2 cm3 of tissue. The materials used were a digital stereotaxic biopsy table (Fischer Imaging) and a Mammotome-gun (Biopsys). A total of 236 patients with 261 predominantly indeterminate lesions (indeterminate: 230; suspicious: 26; malignant: 5) underwent vacuum core biopsy (VCB). Verification was as follows: (a) demonstration of complete or partial removal of the lesion or replacement of the lesion by a small hematoma by comparison of the pre- and post-VCB mammogram; (b) reexcision of 45 malignant and 6 borderline lesions; (c) radiologic-histologic correlation; and (d) 6-month-follow-up mammograms in 129 cases. Two VCBs were not possible because very fine microcalcifications could not be visualized. Two puncture errors occurred which, however, were immediately recognized and VCB was repeated. Based on the above verification a 100 % accuracy was achieved. No relevant side effects occurred. Except for 2 cases mammographically hardly any scarring was visible. Based on the excellent accuracy and excellent tolerance of the procedure VCB appears to be the future method of choice for the workup of those indeterminate mammographically detected lesions that up to now have still required surgical biopsy.