Publications by authors named "Malte Cremer"

24 Publications

  • Page 1 of 1

Mature and immature platelets during the first week after birth and incidence of patent ductus arteriosus.

Cardiol Young 2020 Jun 28;30(6):769-773. Epub 2020 Apr 28.

Department of Neonatology, Charité University Medical Center, Berlin, Germany.

Background: Thrombocytopenia is a risk factor for patent ductus arteriosus. Immature and mature platelets exhibit distinct haemostatic properties; however, whether platelet maturity plays a role in postnatal, ductus arteriosus closure is unknown.

Methods: In this observational study, counts of immature and mature platelets (=total platelet count - immature platelet count) were assessed on days 1, 3, and 7 of life in very low birth weight infants (<1500 g birth weight). We performed echocardiographic screening for haemodynamically significant patent ductus arteriosus on day 7.

Results: Counts of mature platelets did not differ on day 1 in infants with (n = 24) and without (n = 45) haemodynamically significant patent ductus arteriosus, while infants with significant patent ductus arteriosus exhibited lower counts of mature platelet on postnatal days 3 and 7. Relative counts of immature platelets (fraction, in %) were higher in infants with patent ductus arteriosus on day 7 but not on days 1 and 3. Receiver operating characteristic curve analysis unraveled associations between both lower mature platelet counts and higher immature platelet fraction (percentage) values on days 3 and 7, with haemodynamically significant ductus arteriosus. Logistic regression analysis revealed that mature platelet counts, but not immature platelet fraction values, were independent predictors of haemodynamically significant patent ductus arteriosus.

Conclusion: During the first week of postnatal life, lower counts of mature platelets and higher immature platelet fraction values are associated with haemodynamically significant patent ductus arteriosus. Lower counts of mature platelet were found to be independent predictors of haemodynamically significant patent ductus arteriosus.
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http://dx.doi.org/10.1017/S1047951120000943DOI Listing
June 2020

Copper and selenium status as biomarkers of neonatal infections.

J Trace Elem Med Biol 2020 Mar 15;58:126437. Epub 2019 Nov 15.

Institute for Experimental Endocrinology, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. Electronic address:

Neonatal infections are a major risk factor for neonatal mortality. A reliable diagnosis of early-onset sepsis (EOS) is hampered by the variable clinical presentations of the children. We hypothesized that changes in the Se or Cu status, or the biomarkers selenoprotein P (SELENOP) or ceruloplasmin (CP) alone or in combination may be informative of EOS. We generated a new human CP-specific non-competitive immunoassay (ELISA) suitable of analysing small sample volumes and validated the method with a commercial CP source. Using this novel CP assay, we analysed a case-control study of EOS (n = 19 control newborns, n = 18 suspected cases). Concentrations of Se, Cu, SELENOP, CP, interleukin-6 (IL-6), and C-reactive protein (CRP) along with the Cu/Se and CP/SELENOP ratios were evaluated by correlation analyses as biomarkers for EOS. Diagnostic value was estimated by receiver operating characteristic (ROC) curve analyses. The new CP-ELISA displayed a wide working range (0.10-6.78 mg CP/L) and low sample requirement (2 μL of serum, EDTA-, heparin- or citrate-plasma). Plasma CP correlated positively with Cu concentrations in the set of all samples (Pearson r = 0.8355, p < 0.0001). Three of the infected neonates displayed particularly high ratios of Cu/Se and CP/SELENOP, i.e., 3.8- to 6.9-fold higher than controls. Both the Cu/Se and the CP/SELENOP ratios correlated poorly with the early infection marker IL-6, but strongly and positively with the acute-phase protein CRP (Cu/Se-CRP: Spearman ϱ = 0.583, p = 0.011; CP/SELENOP-CRP: ϱ = 0.571, p = 0.013). The ROC curve analyses indicate that a combination of biomarkers for the Se and Cu status do not improve the early identification of EOS considerably. This study established a robust, highly precise, partly validated and scalable novel CP sandwich ELISA suitable for basic and clinical research, requiring minute amounts of sample. The ratio of circulating CP/SELENOP constitutes a promising new composite biomarker for detection of EOS, at least in a subset of severely diseased children.
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http://dx.doi.org/10.1016/j.jtemb.2019.126437DOI Listing
March 2020

[Visceral Leishmaniasis in a Toddler Returning from Vacation in Southern Europe Presenting with Pancytopenia and Fever].

Klin Padiatr 2019 09 17;231(5):269-270. Epub 2019 Jul 17.

Klinik für Pädiatrie m.S. Pneumologie, Immunologie und Intensivmedizin, Charité - Universitätsmedizin Berlin, Deutschland.

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http://dx.doi.org/10.1055/a-0918-6334DOI Listing
September 2019

Association between Platelet Counts before and during Pharmacological Therapy for Patent Ductus Arteriosus and Treatment Failure in Preterm Infants.

Front Pediatr 2018 7;6:41. Epub 2018 Mar 7.

Department of Neonatology, Charité University Medical Center, Berlin, Germany.

Background: The role of platelets for mediating closure of the ductus arteriosus in human preterm infants is controversial. Especially, the effect of low platelet counts on pharmacological treatment failure is still unclear.

Methods: In this retrospective study of 471 preterm infants [<1,500 g birth weight (BW)], who were treated for a patent ductus arteriosus (PDA) with indomethacin or ibuprofen, we investigated whether platelet counts before or during pharmacological treatment had an impact on the successful closure of a hemodynamically significant PDA. The effects of other factors, such as sepsis, preeclampsia, gestational age, BW, and gender, were also evaluated.

Results: Platelet counts before initiation of pharmacological PDA treatment did not differ between infants with later treatment success or failure. However, we found significant associations between low platelet counts during pharmacological PDA therapy and treatment failure ( < 0.05). Receiver operating characteristic (ROC) curve analysis showed that platelet counts after the first, and before and after the second cyclooxygenase inhibitor (COXI) cycle were significantly associated with treatment failure (area under the curve of >0.6). However, ROC curve analysis did not reveal a specific platelet cutoff-value that could predict PDA treatment failure. Multivariate logistic regression analysis showed that lower platelet counts, a lower BW, and preeclampsia were independently associated with COXI treatment failure.

Conclusion: We provide further evidence for an association between low platelet counts during pharmacological therapy for symptomatic PDA and treatment failure, while platelet counts before initiation of therapy did not affect treatment outcome.
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http://dx.doi.org/10.3389/fped.2018.00041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845986PMC
March 2018

Copper to Zinc Ratio as Disease Biomarker in Neonates with Early-Onset Congenital Infections.

Nutrients 2017 Mar 30;9(4). Epub 2017 Mar 30.

Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, CVK, D-13353 Berlin, Germany.

Copper (Cu) and zinc (Zn) are essential trace elements for regular development. Acute infections alter their metabolism, while deficiencies increase infection risks. A prospective observational case-control study was conducted with infected ( = 21) and control ( = 23) term and preterm newborns. We analyzed trace element concentrations by X-ray fluorescence, and ceruloplasmin (CP) by Western blot. Median concentration of Cu at birth (day 1) was 522.8 [387.1-679.7] μg/L, and Zn was 1642.4 ± 438.1 μg/L. Cu and Zn correlated positively with gestational age in control newborns. Cu increased in infected newborns from day 1 to day 3. CP correlated positively to Cu levels at birth in both groups and on day 3 in the group of infected neonates. The Cu/Zn ratio was relatively high in infected newborns. Interleukin (IL)-6 concentrations on day 1 were unrelated to Cu, Zn, or the Cu/Zn ratio, whereas C-reactive protein (CRP) levels on day 3 correlated positively to the Cu/Zn -ratio at both day 1 and day 3. We conclude that infections affect the trace element homeostasis in newborns: serum Zn is reduced, while Cu and CP are increased. The Cu/Zn ratio combines both alterations, independent of gestational age. It may, thus, constitute a meaningful diagnostic biomarker for early-onset infections.
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http://dx.doi.org/10.3390/nu9040343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5409682PMC
March 2017

Fresh frozen plasma transfusion - a risk factor for pulmonary hemorrhage in extremely low birth weight infants?

J Perinat Med 2017 Jul;45(5):627-633

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Aim: To evaluate risk factors for pulmonary hemorrhage (PH) in extremely low birth weight infants (ELBW) taking into consideration coagulation screens, platelet counts, transfusion of fresh frozen plasma (FFP), and platelet concentrates prior to PH.

Patients And Methods: A retrospective case-control study consisting of 20 ELBW infants with PH and 40 matched controls. Coagulation screens, platelet counts at birth and at onset of PH, and transfusion frequencies prior to PH were compared to case-controls at birth and 24-96 h after birth.

Results: While the initial platelet counts, fibrinogen concentrations, and international normalized ratios were similar in PH infants and controls, the activated partial prothrombin time was prolonged (P=0.05). Compared to 28% of case controls (P<0.05), 55% of infants with later PH received FFP prior to PH. Platelet counts were significantly lower at onset of PH (median 81/nL; range: 37-236/nL) compared to controls (166/nL; 27-460/nL; P<0.005). Multivariate analysis indicated a lack of antenatal steroids, supplemental oxygen, and transfusion of FFP as independent risk factors for PH.

Conclusion: Prolonged activated partial thromboplastin time (aPTT) might be associated with PH. PH does not primarily depend upon severe thrombocytopenia. A developmental mismatch in hemostasis by transfusion of adult donor plasma should be considered a risk factor for PH.
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http://dx.doi.org/10.1515/jpm-2016-0309DOI Listing
July 2017

Selenium status in neonates with connatal infection.

Br J Nutr 2016 Aug 8;116(3):504-13. Epub 2016 Jun 8.

1Institute for Experimental Endocrinology,Charité Universitätsmedizin Berlin,Suedring 10,Campus Virchow-Klinikum,D-13353 Berlin,Germany.

Infectious diseases impair Se metabolism, and low Se status is associated with mortality risk in adults with critical disease. The Se status of neonates is poorly characterised, and a potential impact of connatal infection is unknown. We hypothesised that an infection negatively affects the Se status of neonates. We conducted an observational case-control study at three intensive care units at the Charité-Universitätsmedizin Berlin, Germany. Plasma samples were collected from forty-four neonates. On the basis of clinical signs for bacterial infection and concentrations of IL-6 or C-reactive protein, neonates were classified into control (n 23) and infected (n 21) groups. Plasma Se and selenoprotein P (SePP) concentrations were determined by X-ray fluorescence and ELISA, respectively, at day of birth (day 1) and 48 h later (day 3). Se and SePP showed a positive correlation in both groups of neonates. Se concentrations indicative of Se deficit in adults (500 ng/l). During antibiotic therapy, SePP increased significantly from day 1 (1·03 (sd 0·10) mg/l) to day 3 (1·34 (sd 0·10) mg/l), indicative of improved hepatic Se metabolism. We conclude that both Se and SePP are suitable biomarkers for assessing Se status in neonates and for identifying subjects at risk of deficiency.
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http://dx.doi.org/10.1017/S0007114516002208DOI Listing
August 2016

Delta-He, Ret-He and a New Diagnostic Plot for Differential Diagnosis and Therapy Monitoring of Patients Suffering from Various Disease-Specific Types of Anemia.

Clin Lab 2016 ;62(4):667-77

Background: The present study was aimed to prove the usefulness of a new diagnostic plot (Hema-Plot), illustrating the relationship between the hemoglobin content of reticulocytes (Ret-He) as a marker of functional iron deficiency and the difference between the reticulocyte and erythrocyte hemoglobin content (Delta-He) as a marker of an impaired hemoglobinization of newly formed reticulocytes occurring during inflammatory processes, to differentiate between various disease-specific types of anemia.

Methods: A complete blood and reticulocyte count was performed on routine EDTA blood samples from 345 patients with and without various disease-specific types of anemia using the Sysmex XN-9000 hematology analyzer: blood healthy newborns (n = 23), blood healthy adults (n = 31), patients suffering from anemia of chronic disease (ACD) due to diverse oncological, chronic inflammatory, or autoimmune diseases (total n = 138) with (n = 65) and without therapy (n = 73), patients with thalassemia and/or hemoglobinopathy (n = 18), patients with iron deficiency anemia (IDA) (n = 35), patients with a combination of ACD and IDA (n = 17), as well as patients suffering from sepsis (total n = 83) with (n = 32) and without therapy (n = 51). The results for Ret-He, Delta-He, and C-reactive protein (CRP) were statistically compared (Mann-Whitney U Test) between the particular patient groups and the diagnostic plots were drawn.

Results: Delta-Hemoglobin showed a statistically significant difference between blood healthy newborns and blood healthy adults (p ≤ 0.05), while Ret-He and C-reactive protein did not. In addition, of all three biomarkers only Delta-He showed a statistically significant difference (p ≤ 0.05) between the ACD/IDA and IDA cohort. Delta-He, Ret-He, and CRP showed a statistically significant difference between patient cohorts with and without therapy suffering from ACD, ACD/IDA, and sepsis before and after medical therapy (p ≤ 0.05). The Hema-Plot illustrated the dynamic character of Ret-He and Delta-He, notably in inflammation-based types of anemia like ACD or ACD/ IDA.

Conclusions: Delta-He is a new biomarker clearly distinguishing between inflammation-based types of anemia before and after medical therapy, as well as between ACD/IDA and IDA. The new Hema-Plot is a helpful tool for differential diagnosis and disease-monitoring in various types of disease-specific anemia, especially in ACD and ACD/IDA. The Hema-Plot can be used to identify non-adherent patients or an insufficient therapy.
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http://dx.doi.org/10.7754/clin.lab.2015.150830DOI Listing
June 2016

The rationale for third trimester testing of vertical HIV transmission in neonates with CMV infection.

Infection 2016 Aug 30;44(4):555-7. Epub 2016 Jan 30.

Department of Neonatology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.

We report on a late-preterm neonate with severe congenital cytomegalovirus (CMV) infection, refractory to antiviral therapy with ganciclovir. Subsequent immune diagnostics led to the finding of HIV infection at day 69, even though the mother tested negative for HIV in early pregnancy. Thus, in congenital CMV infection, HIV testing should be performed to elucidate maternal HIV seroconversion during late pregnancy. Our case strongly supports third trimester screening of HIV infection acquired during pregnancy, yet recommended only for women with traditional risk factors for HIV or living in an area of high HIV prevalence.
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http://dx.doi.org/10.1007/s15010-016-0876-0DOI Listing
August 2016

Thrombocytopenia and platelet transfusion in the neonate.

Semin Fetal Neonatal Med 2016 Feb 19;21(1):10-8. Epub 2015 Dec 19.

Department of Neonatology, Charité - Universitätsmedizin Berlin, Germany.

Neonatal thrombocytopenia is widespread in preterm and term neonates admitted to neonatal intensive care units, with up to one-third of infants demonstrating platelet counts <150 × 10(9)/L. Thrombocytopenia may arise from maternal, placental or fetal/neonatal origins featuring decreased platelet production, increased consumption, or both mechanisms. Over the past years, innovations in managing neonatal thrombocytopenia were achieved from prospectively obtained clinical data on thrombocytopenia and bleeding events, animal studies on platelet life span and production rate and clinical use of fully automated measurement of reticulated platelets (immature platelet fraction). This review summarizes the pathophysiology of neonatal thrombocytopenia, current management including platelet transfusion thresholds and recent developments in megakaryopoietic agents. Furthermore, we propose a novel index score for bleeding risk in thrombocytopenic neonates to facilitate clinician's decision-making when to transfuse platelets.
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http://dx.doi.org/10.1016/j.siny.2015.11.001DOI Listing
February 2016

Nucleated red blood cells as marker for an increased risk of unfavorable outcome and mortality in very low birth weight infants.

Early Hum Dev 2015 Oct 25;91(10):559-63. Epub 2015 Jul 25.

Department of Neonatology, Charité-Universitätsmedizin Berlin, Germany.

Background: Nucleated red blood cells (NRBC) are normoblastic cells that failed to extrude their nuclei before exiting from bone marrow or liver. While NRBC are frequently found in umbilical cord blood after fetal distress, NRBC counts drop rapidly after birth.

Aims: To determine the predictive value of the NRBC count during the first 120h after birth as marker for later risk of unfavorable outcome in very preterm infants.

Study Design: This cohort study investigated the association between absolute count of NRBC on admission (day 1), the mean NRBC count between day 2 to 5, and outcome (mortality or the composite outcome of mortality and severe morbidity).

Results: 438 infants with a gestational age<32weeks and a birth weight<1500g were included within a five-year period, of whom 46 patients died and 65 suffered from severe morbidity. Nonsurvivors had significantly higher NRBC counts between day 2 and 5, as compared to survivors. This finding was observed in infants both appropriate and small for gestational age. An increase of 10/nL of the mean NRBC count on postnatal day 2 to 5 had an odds ratio for mortality of 6.95 (95% CI 2.21-21.86) and an odds ratio for the composite outcome mortality and severe morbidity of 3.43 (95% CI 1.43-8.24). The optimal cut-off value for prediction of death was NRBC >2/nL with a sensitivity of 85% and a specificity of 75%.

Conclusions: Elevation of NRBC on postnatal day 2 to 5 is an independent predictor of mortality in preterm infants.
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http://dx.doi.org/10.1016/j.earlhumdev.2015.06.004DOI Listing
October 2015

Persistent pure red cell aplasia in dicygotic twins with persistent congenital parvovirus B19 infection-remission following high dose intravenous immunoglobulin.

Eur J Pediatr 2014 Dec 2;173(12):1723-6. Epub 2014 Oct 2.

Pediatric Pulmonology/Immunology, Charité University Medical Center Berlin, Berlin, Germany,

Unlabelled: We report the course of dicygotic twins born preterm after 29 (4)/7 weeks of gestation due to congenital Parvovirus B19 infection causing fetal hydrops with severe anemia in one infant in whom intrauterine transfusion was impossible to perform and high levels of viremia in both infants. After being discharged, they were readmitted at 3 months of age with critical aplastic crisis. Therapy with intravenous immunoglobulin infusion resulted in decreasing viremia followed by stable hemoglobin levels in both infants.

Conclusion: Intravenous immunoglobulin treatment of congenital pure red cell aplasia due to Parvovirus B19 infection in preterm infants seems to be effective to introduce viral remission and to normalize erythropoiesis.
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http://dx.doi.org/10.1007/s00431-014-2420-5DOI Listing
December 2014

Nasal high-frequency oscillation ventilation in neonates: a survey in five European countries.

Eur J Pediatr 2015 Apr 18;174(4):465-71. Epub 2014 Sep 18.

Department of Neonatology, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany,

Unlabelled: Nasal high-frequency oscillation ventilation (nHFOV) is a non-invasive ventilation mode that applies an oscillatory pressure waveform to the airways using a nasal interface. nHFOV has been shown to facilitate carbon dioxide expiration, but little is known about its use in neonates. In a questionnaire-based survey, we assessed nHFOV use in neonatal intensive care units (NICUs) in Austria, Switzerland, Germany, the Netherlands, and Sweden. Questions included indications for nHFOV, equipment used, ventilator settings, and observed side effects. Of the clinical directors of 186 NICUs contacted, 172 (92 %) participated. Among those responding, 30/172 (17 %) used nHFOV, most frequently in premature infants <1500 g (27/30) for the indication nasal continuous positive airway pressure (nCPAP) failure (27/30). Binasal prongs (22/30) were the most common interfaces. The median (range) mean airway pressure when starting nHFOV was 8 (6-12) cm H2O, and the maximum mean airway pressure was 10 (7-18) cm H2O. The nHFOV frequency was 10 (6-13) Hz. Abdominal distension (11/30), upper airway obstruction due to secretions (8/30), and highly viscous secretions (7/30) were the most common nHFOV side effects.

Conclusion: In a number of European NICUs, clinicians use nHFOV. The present survey identified differences in nHFOV equipment, indications, and settings. Controlled clinical trials are needed to investigate the efficacy and side effects of nHFOV in neonates.
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http://dx.doi.org/10.1007/s00431-014-2419-yDOI Listing
April 2015

Mice over-expressing human erythropoietin indicate that erythropoietin enhances expression of its receptor via up-regulated Gata1 and Tal1.

Haematologica 2014 Oct 1;99(10):e205-7. Epub 2014 Aug 1.

Department of Neonatology, Charité - Universitätsmedizin Berlin, Germany

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http://dx.doi.org/10.3324/haematol.2014.104844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4181272PMC
October 2014

Neonatal outcome in infants of patients with radical vaginal trachelectomy.

J Perinat Med 2012 Sep;40(5):503-9

Department of Gynecology, Charité-University Medicine Berlin, Berlin, Germany.

Objective: Radical vaginal trachelectomy (RVT) as a fertility-preserving surgery in patients with early-stage cervical cancer is proven to be oncologically safe. After RVT, pregnancy rates vary between 40 % and 80 %. Outcome of infants is complicated by a preterm delivery rate of 30 – 50 %. We investigated pregnancy and neonatal outcome after RVT.

Methods: A total of 154 patients with cervical cancer underwent RVT between March 1995 and February 2008. Desire to conceive, pregnancy data, and neonatal outcome were prospectively recorded. Infants’ data were pair-matched to data of a control group according to weeks of gestation. Bayley scales of infant development scores were recorded in the group of preterm-delivered infants.

Results: Fifty-five women who underwent RVT gave birth to 58 children. Twenty-five (43 %) pregnancies were complicated by preterm rupture of membranes. Thirty infants (52 %) were born preterm, of with 17 (29 %) were < 32 gestational weeks (GW) and seven (12 %) were < 28 GW. There were significantly more premature rupture of membranes in pregnancies after RVT. Despite a higher occurrence of postnatal infections in newborns of mothers who underwent RVT, long-term outcomes are not affected negatively. Regarding overall morbidity, a trend to fewer postnatal complications, compared with the control group, was found.

Conclusion: Postnatal morbidity in infants of women who underwent RVT, based on trend, is decreased compared with controls. Intense medical observation and treatment during pregnancy, birth, and neonatal period may explain this finding. Neonates in the RVT group have a non-significantly elevated risk for postnatal infections. They do not show an additional risk due to the maternal operation. Their long-term postnatal outcome is not affected negatively.
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http://dx.doi.org/10.1515/jpm-2012-0045DOI Listing
September 2012

Human birth observed in real-time open magnetic resonance imaging.

Am J Obstet Gynecol 2012 Jun 13;206(6):505.e1-6. Epub 2012 Jan 13.

Department of Obstetrics, Charité University Hospital Berlin, Berlin, Germany.

Objective: Knowledge about the mechanism of labor is based on assumptions and radiographic studies performed decades ago. The goal of this study was to describe the relationship between the fetus and the pelvis as the fetus travels through the birth canal, using an open magnetic resonance imaging (MRI) scanner.

Study Design: The design of the study used a real-time MRI series during delivery of the fetal head.

Results: Delivery occurred by progressive head extension. However, extension was a very late movement that was observed when the occiput was in close contact with the inferior margin of the symphysis pubis, occurring simultaneously with gliding downward of the fetal head.

Conclusion: This observational study shows, for the first time, that birth can be analyzed with real-time MRI. MRI technology allows assessment of maternal and fetal anatomy during labor and delivery.
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http://dx.doi.org/10.1016/j.ajog.2012.01.011DOI Listing
June 2012

Platelet transfusions in neonates: practices in the United States vary significantly from those in Austria, Germany, and Switzerland.

Transfusion 2011 Dec 9;51(12):2634-41. Epub 2011 Jun 9.

Department of Neonatology and the Institute for Social Medicine, Epidemiology and Health Economics, Charité-Universitätsmedizin, Berlin, Germany.

Background: Thrombocytopenia affects 20% to 35% of patients admitted to neonatal intensive care units (NICUs). Platelet (PLT) transfusions are usually administered to neonates with thrombocytopenia at higher thresholds than those used for older children or adults, although there is a paucity of evidence to guide these decisions.

Study Design And Methods: In this study, we used a Web-based survey to investigate the PLT transfusion thresholds used in Level 1 NICUs (equivalent to Level 3 in the US) in three European countries (Austria, Germany, and Switzerland [AUT/GER/SUI]). This survey was identical to the one that was previously sent to US neonatologists, thus allowing for a direct comparison of their responses to 11 case-based scenarios.

Results: In nine of the scenarios, AUT/GER/SUI neonatologists selected substantially lower PLT transfusion thresholds than US neonatologists (p < 0.0001). Transfusion thresholds were more similar when treating neonatal alloimmune thrombocytopenia and before invasive procedures. The clinical impact of these differences was estimated by extrapolating the AUT/GER/SUI versus the US answers to a cohort of neonates with a birth weight below 1000 g. This suggested that, in AUT/GER/SUI, these neonates would receive 167 PLT transfusions per 1000 infants, compared to 299 PLT transfusions in the United States.

Conclusion: This first international comparative survey on PLT transfusion practice in neonates reveals substantially higher transfusion thresholds in the United States than in AUT/GER/SUI. Well-designed clinical studies are needed to address the risks and/or benefits of these different approaches.
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http://dx.doi.org/10.1111/j.1537-2995.2011.03208.xDOI Listing
December 2011

Granularity Index of the SYSMEX XE-5000 hematology analyzer as a replacement for manual microscopy of toxic granulation neutrophils in patients with inflammatory diseases.

Clin Chem Lab Med 2011 Jul 17;49(7):1193-8. Epub 2011 May 17.

Institute of Laboratory Medicine and Pathobiochemistry, Charité Universitätsmedizin Berlin, Berlin, Germany.

Background: When certain inflammatory processes occur, toxic granulation neutrophils (TGNs) appear in the blood showing prominent cytoplasmic granules. Currently, the granularity of TGNs is analyzed by manual microscopy of blood smears. The SYSMEX XE-5000 is an automated hematology analyzer, which can measure toxic granulation of TGNs by calculating the Granularity (GI) Index. In this study we investigated if the GI-Index is suitable as a parameter for the TGN granularity in inflammatory diseases.

Methods: An evaluation of the toxic granulation neutrophil (TGN) granularity by manual microscopy, the GI-Index and the C-reactive protein (CRP) concentrations of 158 patients were determined. Blood samples from 40 healthy individuals were incubated with lipopolysaccharide (LPS) for in vitro kinetic measurements of the GI-Index. Furthermore, time course measurements of the GI-Index and CRP concentrations of 100 intensive care unit patients were performed.

Results: The GI-Index correlated with the microscopic rating of TGNs (n=158; r(s)=0.839; p<0.0001). When incubating the blood samples with LPS, the neutrophils displayed hypogranulation 30 min after incubation and a hypergranulation after 90 min. In vivo, the GI-Index indicated changes of the bacterial infection status 1 day earlier than the CRP concentration. The correlation of CRP and GI-Index varied between the patient cohorts (n=158; r(s)=0.836) (n=100; r=0.177), depending on the cause and extent of inflammation.

Conclusions: The GI-Index is suited to quantify the granularity of TGNs. The GI-Index is an automated, standardized parameter available on a 24 h basis. We suggest that it replace the time-consuming, subjective and semiquantitative microscopic procedure.
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http://dx.doi.org/10.1515/CCLM.2011.188DOI Listing
July 2011

Immature platelet values indicate impaired megakaryopoietic activity in neonatal early-onset thrombocytopenia.

Thromb Haemost 2010 May 9;103(5):1016-21. Epub 2010 Mar 9.

Department of Neonatology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany.

Newly released platelets, referred to as immature platelets, can be reliably quantified based on their RNA content by flow cytometry in an automated blood analyser. The absolute number of immature platelets (IPF#) and the immature platelet fraction (IPF%) reflect megakaryopoietic activity. We aimed to analyse the implication of these parameters in analysing the pathomechanism of early-onset neonatal thrombocytopenia. Platelet counts and IPF were determined at day 1 to 3 (d1 to d3) in 857 neonates admitted to intensive care. In thrombocytopenic patients (platelet counts<150 x 10(9)/l, n=129), IPF# was significantly lower (8.5 +/- 2.7 x 10(9)/l), than in non-thrombocytopenic neonates (9.5 +/- 3.6 x 10(9)/l, n=682, p<0.05). IPF% was significantly higher in thrombocytopenic (9.3 +/- 7.9%) vs. non-thrombocytopenic neonates (4.1 +/- 1.8%, p<0.001). While neonates with early-onset infection (n=134) had lower platelet counts (199 +/- 75 x 10(9)/l) compared to controls (230 +/- 68 x 10(9)/l, n=574, p<0.01), there were no differences in IPF# or IPF%. Likewise, "small for gestational age" infants (SGA, n=149) had lower platelet counts at d1 (199 +/- 75 x 10(9)/l, p<0.001) than controls, but no differences in IPF. A trend towards lower IPF# was detected if SGA infants with platelet counts <100 x 10(9)/l (5.4 +/- 3.9 x 10(9)/l, n=11) and thrombocytopenic neonates with infection (9.9 +/- 7.3 x 10(9)/l, n=10, p=0.11) were compared. The evaluation of IPF# indicates that thrombocytopenia in neonates is likely due to a combination of increased platelet consumption and inadequate megakaryopoietic response by the neonatal bone marrow. Furthermore, SGA neonates with moderate and severe thrombocytopenia might have a pronounced suppression of megakaryopoiesis compared to neonates with infection.
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http://dx.doi.org/10.1160/TH09-03-0148DOI Listing
May 2010

Diagnosis and treatment of maternal acute myeloid leukemia during pregnancy imitating HELLP syndrome.

J Perinat Med 2009 ;37(6):713-4

Department of Obstetrics CVK, Charité University Hospital, Berlin, Germany.

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http://dx.doi.org/10.1515/JPM.2009.105DOI Listing
February 2010

TRAIL: Activation of ERK1/2 Protects Cells Against Apoptosis.

Authors:
Malte Cremer

Cancer Invest 2005 ;23(7):651

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http://dx.doi.org/10.1080/07357900500283168DOI Listing
January 2006

A therapy-refractory neonatal auto-immune thrombocytopenia treated with anti-D.

Eur J Pediatr 2004 Mar 23;163(3):183-4. Epub 2003 Dec 23.

Klinik für Allgemeine Pädiatrie, Charité, Universitätsmedizin Berlin, Berlin, Germany.

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http://dx.doi.org/10.1007/s00431-003-1390-9DOI Listing
March 2004

Longitudinal thrombopoietin plasma concentrations in fetuses with alloimmune thrombocytopenia treated with intrauterine PLT transfusions.

Transfusion 2003 Sep;43(9):1216-22

Department of Neonatology, University of Bonn, Bonn, Germany.

Background: The purpose of this study was to describe longitudinal thrombopoietin (TPO) plasma concentrations in fetuses with fetomaternal alloimmune thrombocytopenia (FMAIT).

Study Design And Methods: Group 1 was the control group, 8 fetuses with normal hematopoiesis. Group 2 consisted of 4 nonthrombocytopenic fetuses with fetomaternal human PLT antigen incompatibility. Group 3 consisted of 14 fetuses with prenatal-diagnosed severe FMAIT owing to human PLT antigen-1a incompatibility. Fetal PLT counts, MoAb-specific immobilization of PLT antigen score, and TPO plasma concentrations were measured in a total number of 94 serial samples taken by cordocentesis before intrauterine PLT transfusion.

Results: Normal fetal TPO plasma concentrations ranged between 15 and 119 pg per mL (Group 1 median, 67 pg/mL). In fetuses with risk of FMAIT but normal PLT counts, TPO concentrations were normal (Group 2 median, 72 pg/mL; range, <15-158 pg/mL). In FMAIT with thrombocytopenia, the median TPO concentration was significantly higher than in Groups 1 and 2 (Group 3 median, 172 pg/mL; range, 15-623 pg/mL; p < 0.001). In the longitudinal analysis, TPO concentrations remained constant (n = 8), peaked only transiently (n = 3), or increased at the end of gestation (n = 3). Elevated TPO concentrations (592 and 623 pg/mL) were detected in one patient, who already had intracranial hemorrhage in utero.

Conclusion: TPO concentrations are normal or slightly elevated in FMAIT. Further clinical information can be provided by the longitudinal analysis of TPO concentrations in severe FMAIT.
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http://dx.doi.org/10.1046/j.1537-2995.2003.00489.xDOI Listing
September 2003