Claudia Nussbaum

Ludwig-Maximilians-University of Munich | LMU · Department of Paediatrics

Background: Multisystem inflammatory syndrome in children (MIS-C)/pediatric inflammatory multisystem syndrome (PIMS) is a rare but severe hyperinflammation following exposure to SARS-CoV-2. The exact pathogenesis is unknown, but SARS-CoV-2 is linked to vascular-endothelial pathology. We therefore longitudinally analyzed endothelial function and mic...

Newborns are at high risk of developing neonatal sepsis, particularly if born prematurely. This has been linked to divergent requirements the immune system has to fulfill during intrauterine compared to extrauterine life. By transcriptomic analysis of fetal and adult neutrophils we set out to shed new light on the molecular mechanisms of neutrophil...

Background: Monitoring of the macrocirculation during surgery provides limited information on the quality of organ perfusion. Objective: We investigated the feasibility of perioperative microcirculatory measurements in children. Methods: Sublingual microvessels were visualized by handheld videomicroscopy in 11 children (19 mo - 10 yrs) undergo...

Introduction: SARS-CoV-2 can cause a severe post infectious infammation, called Multisystem Infammatory Syndrome in Children (MIS-C)/Pediatric Infammatory Multisystem Syndrome (PIMS), which shows clinical similarities to the toxic shock syndrome (TSS) and the Kawasaki syndrome (KS). Since SARS-CoV-2 has serious impacts on the endothelial vascular s...

The factors influencing weaning of preterm infants from noninvasive ventilation (NIV) are poorly defined and the weaning decisions are often driven by subjective judgement rather than objective measures. To standardize quantification of respiratory effort, the Silverman-Andersen Score (SAS) was included in our nursing routine. We investigated the f...

Aims Kawasaki disease (KD) is an acute systemic vasculitis with possible long-term impact of general cardio-vascular health. An endothelial glycocalyx disorder during the disease's acute phase might predispose to long-term vascular anomalies leading to endothelial dysfunction and atherosclerosis. To investigate any association between increased car...

The endothelial glycocalyx (EG) as part of the endothelial surface layer (ESL) is an important regulator of vascular function and homeostasis, including permeability, vascular tone, leukocyte recruitment and coagulation. Located at the interface between the endothelium and the blood stream, this highly fragile structure is prone to many disruptive...

Purpose The MUNICH Preterm and Term Clinical (MUNICH-PreTCl) birth cohort was established to uncover pathological processes contributing to infant/childhood morbidity and mortality. We collected comprehensive medical information of healthy and sick newborns and their families, together with infant blood samples for proteomic analysis. MUNICH-PreTCl...

Methadone, or in Germany levomethadone, may be used for the treatment of iatrogenic opioid withdrawal syndrome in pediatric intensive care units. The limited literature on opioid rotation in children does not provide data for the switch from methadone to another opioid. We report switching a very ill preterm baby in an unstable condition from IV le...

Prematurity predisposes to cardiovascular disease; however the underlying mechanisms remain elusive. Disturbance of the endothelial glycocalyx (EG), an important regulator of vessel function, is thought to contribute to vascular pathology. Here, we studied the EG with respect to gestational and postnatal age in preterm and term neonates. The Perfus...

Antibiotic consumption (AC) is a key component of antimicrobial stewardship programs to recognize local patterns of antibiotic use. Our aim was to measure AC in neonatal units, including neonatal (NICU)/paediatric (PICU) intensive care units in different countries. We conducted a multicenter, retrospective, cohort study in three NICUs, one neonatal...

Background: Hypotension and bradycardia are known side effects of general anesthesia, while little is known about further macro- and microhemodynamic changes during induction. Intriguing is furthermore, why some patients require no vasopressor medication to uphold mean arterial pressure, while others need vasopressor support. Objective: Determin...

Background: Preterm infants are at increased risk for hypertension in adolescence. Microcirculatory dysfunction has been identified as an underlying cause for cardiovascular disease. Our goal was to document the development of the cutaneous microcirculation in preterm infants during the first weeks of life and to compare it to the situation in term...

Although the hemostatic potential of adult platelets has been investigated extensively, regulation of platelet function during fetal life is less clear. Recent studies have provided increasing evidence for a developmental control of platelet function during fetal ontogeny. Fetal platelets feature distinct differences in reactive properties compared...

Ichthyoses comprise a clinically and genetically heterogeneous group of hereditary cornification disorders, leading to a disturbed barrier function of the skin. Rare non-syndromic forms of ichthyosis present at birth are referred to as autosomal-recessive congenital ichthyoses (ARCI). ARCI are clinically subdivided into lamellar ichthyosis (LI), co...

Objective: Platelet function has been intensively studied in the adult organism. However, little is known about the function and hemostatic capacity of platelets in the developing fetus as suitable in vivo models are lacking. Approach and results: To examine fetal platelet function in vivo, we generated a fetal thrombosis model and investigated...

Neutrophils need to penetrate the perivascular basement membrane for successful extravasation into inflamed tissue, but this process is incompletely understood. Recent findings have associated mammalian sterile 20-like kinase 1 (MST1) loss of function with a human primary immunodeficiency disorder, suggesting that MST1 may be involved in immune cel...

Objective: Perturbation of the endothelial glycocalyx is discussed in the pathogenesis of complications related to cardiopulmonary bypass. We evaluated the effects of cardiopulmonary bypass on the microcirculation and the microvascular endothelial glycocalyx of infants undergoing surgery for congenital cardiac defects. Methods: The microcirculat...

Myeloid-related proteins (MRPs) 8 and 14 are cytosolic proteins secreted from myeloid cells as proinflammatory mediators. Currently, the functional role of circulating extracellular MRP8/14 is unclear. Our present study identifies extracellular MRP8/14 as an autocrine player in the leukocyte adhesion cascade. We show that E-selectin-PSGL-1 interact...

Sphingosine-1-phosphate (S1P) participates in inflammation; however, its role in leukocyte rolling is still unclear. Here we use intravital microscopy in inflamed mouse cremaster muscle venules and human endothelial cells to show that S1P contributes to P-selectin-dependent leukocyte rolling through endothelial S1P receptor 3 (S1P3) and Galphaq, PL...

Background: There is no doubt today about the existence of the endothelial glycocalyx (EG) and its decisive role in maintaining vascular homeostasis in adult humans. Shedding of the EG has been demonstrated in adults with sepsis or trauma, in patients undergoing major operations, and after ischemia/reperfusion. The aim of the present study was to d...

To evaluate the microcirculation of children with type 1 diabetes mellitus who demonstrate no clinical signs of diabetic microangiopathy for the presence of microvascular alterations and glycocalyx perturbation. Images of sublingual vessels were obtained in 14 children with diabetes (ages 12.8 ± 2.8 years, diabetes duration 6.7 ± 4.3 years) and 14...

The facilitated recruitment of vascular progenitor cells (VPCs) to ischemic areas might be a therapeutic target for neovascularisation and repair. However, efficient and directed attraction of VPCs remains a major challenge in clinical application. To enhance VPC homing we developed a fusion protein (S1FG), based on the biology of SDF-1/CXCL12 and...

In adult mammals, leukocyte recruitment follows a well-defined cascade of adhesion events enabling leukocytes to leave the circulatory system and transmigrate into tissue. Currently, it is unclear whether leukocyte recruitment proceeds in a similar fashion during fetal development. Considering the fact that the incidence of neonatal sepsis increase...

Recruitment of polymorphonuclear neutrophils (PMNs) to sites of acute inflammation critically depends on β2 integrins (CD11/CD18). Recently, the mammalian actin-binding protein 1 (mAbp1) was identified as an important adaptor protein regulating PMN trafficking downstream of β2 integrins. Here, we show that mAbp1 constitutively co-immunoprecipitated...

Leukocyte recruitment is ontogenetically regulated during fetal life, with strongly impaired adhesiveness of fetal leukocytes and endothelial cells, during early fetal development. Attenuation of the immune response contributes to the high rate of neonatal infections, particularly in premature infants. Whereas our knowledge of innate immune functio...

Significance: The heme-enzyme myeloperoxidase (MPO) is one of the major neutrophil bactericidal proteins and is stored in large amounts inside azurophilic granules of neutrophils. Upon cell activation, MPO is released and extracellular MPO has been detected in a wide range of acute and chronic inflammatory conditions. Recent ADVANCES AND CRITICAL...

Binding of selectins to their glycan ligands is a prerequisite for successful leukocyte trafficking. During synthesis and transport through the secretory pathway, selectin ligands are constructed with the participation of one or more sialyltransferases of the ST3Gal subfamily. Previous studies established that ST3Gal-IV only partially contributes t...

Cell surface mucins configure the cell surface by presenting extended protein backbones that are heavily O-glycosylated. The glycopeptide structures establish physicochemical properties at the cell surface that enable and block the formation of biologically important molecular complexes. Some mucins, such as MUC1, associate with receptor tyrosine k...

Recruitment of innate immune cells from the vasculature into infected tissue is a key event in primary host defense against invading pathogens. This highly regulated process requires a functional interplay of specialized adhesion molecules and involves a series of steps leading from rolling of leukocytes along the endothelium to firm adhesion and f...

Neutrophils form a vital part of the innate immune response, but at the same time their inappropriate activation contributes to autoimmune diseases. Many molecular components are involved in fine-tuning neutrophil function. We report here the first characterization of the role of ARAP3, a PI3K and Rap-regulated GTPase-activating protein for RhoA an...

Recruitment of polymorphonuclear neutrophils (PMNs) remains a paramount prerequisite in innate immune defense and a critical cofounder in inflammatory vascular disease. Neutrophil recruitment comprises a cascade of concerted events allowing for capture, adhesion and extravasation of the leukocyte. Whereas PMN rolling, binding, and diapedesis are we...

Pediatric Research publishes original papers, invited reviews, and commentaries on the etiologies of diseases of children and disorders of development, extending from molecular biology to epidemiology. Use of model organisms and in vitro techniques relevant to developmental biology and medicine are acceptable, as are translational human studies.

To the editor: Sepsis is one of the leading morbidity and mortality factors in newborns, occurring in more than 700 of every 100 000 live births.[1][1] Newborns seem to have a unique susceptibility to early bacterial infections[2][2] compared with adults, but the underlying pathomechanisms are

In adults with severe sepsis, the disturbances of the sublingual microcirculation can be quantified with orthogonal polarization spectral imaging. We investigated the cutaneous microcirculation of preterm infants with proven infection (PosInf) and with suspected but unproven infection (NegInf). In 25 infants, orthogonal polarization spectral images...

Hintergrund: Der Einsatz von Leitlinien hat einen zuneh-menden Stellenwert in der medizinischen Versorgung einge-nommen. Im hausärztlichen Bereich hat sich die Deutsche Ge-sellschaft für Allgemeinmedizin und Familienmedizin (DE-GAM) zur Aufgabe gemacht, wissenschaftlich fundierte und praxiserprobte Leitlinien zu erstellen. Wir entwickelten erst-mal...

Changes in microcirculation have been recognized as central to many disease processes. The aim of this study was to evaluate factors, which influence the microcirculation of the skin during the first month of life in premature infants. Red blood cell (RBC) velocity, vessel diameter, and functional small vessel density (FSVD) were measured daily for...

Paclitaxel encapsulated in cationic liposomes (EndoTAG-1) significantly impairs tumor growth by a significant reduction of functional tumor microcirculation and induction of endothelial cell apoptosis. The aim of the study was to analyze whether platelet activation within the tumor microcirculation contributes to the antivascular effects of vascula...

The participation of doctors in Continuing Medical Education (CME) activities provided by medical journals increases. Therefore, their quality and efficacy need to be evaluated. This study evaluated the quality of the multiple-choice questions (MCQs) as evaluation tool of CME activities in three German medical journals (Der Internist, Deutsches Arz...