an-advanced-co-culture-model-human-blood-cerebrospinal-fluid-barrier

An Advanced Co-Culture Model of the Human Blood-Cerebrospinal Fluid Barrier for Separate Analysis of Choroid Plexus Epithelium and Endothelium

The highly perfused choroid plexus (CP), located in the ventricular system of the brain, consists of several structural components, including a cuboid ...

Heidelberg University

Systemic Candidia infections are of major concern in neonates, especially in those with risk factors such as longer use of broad spectrum antibiotics. Recent studies showed that also term babies with underlying gastrointestinal or urinary tract abnormalities are much more prone to systemic Candida infection. We report a very rare case of candidiasis caused by Candida kefyr in a term neonate.

Candidiasis caused by Candida kefyr in a neonate: case report.

Infant formulae and food products marketed for children have been increasingly supplemented with probiotics and/or prebiotics. A vast number of studies have accounted for the transit of probiotic use from alternative to more evidence-based medicine. Data support the use of certain probiotics for the adjunct treatment of acute viral gastroenteritis, and for prevention of gastrointestinal diseases. Further roles of prebiotics and probiotics are seen in the prevention of overall infectious diseases and respiratory infections. Data from well-conducted randomized-controlled trials support the therapeutic role for probiotics toward necrotizing enterocolitis in preterm infants. However, it is difficult to translate heterogeneous-based study results, which are mainly due to varying genera, strains, doses, study settings and measured outcomes, into evidence-based recommendations. This article focuses on the evidence of clinical benefits of prebiotics, probiotics and synbiotics toward prevention and treatment of pediatric infectious diseases.

The role of prebiotics and probiotics in prevention and treatment of childhood infectious diseases.

Human milk oligosaccharides help to prevent infectious diseases in breastfed infants. Larger scale testing, particularly in animal models and human clinical studies, is still limited due to shortened availability of more complex oligosaccharides. The purpose of this study was to evaluate 2'-fucosyllactose (2'-FL) and 3-fucosyllactose (3-FL) synthesized by whole-cell biocatalysis for their biological activity in vitro. Therefore, we have tested these oligosaccharides for their inhibitory potential of pathogen adhesion in two different human epithelial cell lines. 2'-FL could inhibit adhesion of Campylobacter jejuni, enteropathogenic Escherichia coli, Salmonella enterica serovar fyris, and Pseudomonas aeruginosa to the intestinal human cell line Caco-2 (reduction of 26%, 18%, 12%, and 17%, respectively), as could be shown for 3-FL (enteropathogenic E coli 29%, P aeruginosa 26%). Furthermore, adherence of P aeruginosa to the human respiratory epithelial cell line A549 was significantly inhibited by 2'-FL and 3-FL (reduction of 24% and 23%, respectively). These results confirm the biological and functional activity of biotechnologically synthesized human milk oligosaccharides. Mass-tailored human milk oligosaccharides could be used in the future to supplement infant formula ingredients or as preventatives to reduce the impact of infectious diseases.

Bioengineered 2'-fucosyllactose and 3-fucosyllactose inhibit the adhesion of Pseudomonas aeruginosa and enteric pathogens to human intestinal and respiratory cell lines.

Anaphylaxis is a life-threatening event. The aim of this study was to estimate the annual frequency of anaphylaxis after immunization in individuals younger than 18 years in Germany leading to hospitalization.

Anaphylaxis After Immunization of Children and Adolescents in Germany.

OBJECTIVE To determine the prevalence of multidrug-resistant organisms (MDROs) colonizing in pediatric refugees admitted to a University Children Hospital in Germany. DESIGN Retrospective observational study. SETTING General pediatric and pediatric surgery units. PATIENTS In Germany, recommendations for MDRO screening of pediatric refugees were recently published. According to these and institutional recommendations, all hospitalized pediatric refugees were screened for MDROs between October 2015 and March 2016. METHODS Using electronic surveillance data, we performed a chart review to identify the prevalence of MDROs among and the clinical diagnoses of pediatric refugees. RESULTS Among 325 patients hospitalized for various causes, most frequently gastroenteritis (30.9%), MDROs were detected in 33.8%. Most of these patients were colonized with multidrug-resistant Gram-negative (MRGN) bacteria (113 isolates), mostly 2MRGN/ESBL (87 isolates); some patients were colonized with methicillin-resistant Staphylococcus aureus (MRSA, 22 isolates); and 1 patient was colonized with vancomycin-resistant enterococci (VRE). Among 110 refugee patients, we detected single colonization with an MDRO in 84 patients (76.4%), co-colonization with 2 pathogens in 23 patients (20.9%), and triple colonization in 3 patients (2.7%). However, infections with MDROs occurred in only 3.6% of pediatric refugees. The peak of positive MDRO screening results in 2015 correlated with an increased hospitalization rate. CONCLUSION Implementation of infection control measures among pediatric refugees is challenging. Due to the high frequency of MDROs in these patients, current screening, isolation, and treatment strategies may have to be adapted. Infect Control Hosp Epidemiol 2016;1-5.

Prevalence of Multidrug-Resistant Organisms in Hospitalized Pediatric Refugees in an University Children's Hospital in Germany 2015-2016.

If a gold standard is lacking in a diagnostic test accuracy study, expert diagnosis is frequently used as reference standard. However, interobserver and intraobserver agreements are imperfect. The aim of this study was to quantify the reproducibility of a panel diagnosis for pediatric infectious diseases.

Expert panel diagnosis demonstrated high reproducibility as reference standard in infectious diseases.

A 28-Day-Old Boy with Multifocal Osteomyelitis Mimicking Non-Accidental Injury.

 () is a common causative pathogen of community-acquired pneumonia. Here, we report the development of macrolide resistance during a school outbreak of severe  infections in southwest Germany. We conducted a case series to assess the clinical and laboratory characteristics of hospitalized children with  infection and the prevalence of macrolide-resistant  (MRMP) in this patient group. We retrospectively analyzed 23 children with serologically (19 patients) and/or PCR (eight patients) confirmed  infection between October 2019 and December 2019. Most of the 15 hospitalized patients had lower respiratory tract infection (n = 10) and required oxygen therapy (83%). The median length of hospitalization was 7 days (range 3-10 days). In 8/15 patients (53.3%) azithromycin and in 4/15 (26.6%) clarithromycin treatment was applied. However, among the five patients for which extended molecular characterization was performed, sequencing of 23S rRNA revealed no mutation only in the first case, but development of macrolide resistance A2058G in four subsequent cases. Hence, we identified a cluster of hospitalized patients with emerging MRMP. Further studies are warranted to confirm a potential link between macrolide resistance and disease severity.

Emergence of Macrolide-Resistant  during an Outbreak in a Primary School: Clinical Characterization of Hospitalized Children.

(1) Background: Although published recommendations are available, the use of antibiotics in non-typhoidal  (NTS) infections in children is still controversially debated in clinical practice. Patients might even be put at risk, with necessary antibiotic therapy being withheld due to the widespread concern of prolonged post-convalescent shedding. The authors conducted a systematic review to assess whether antibiotic treatment influences fecal excretion or the clinical course in children with NTS infection. (2) Methods: The review was carried out following the PRISMA guidelines. In a Medline database search, studies assessing the influence of antibiotic therapy on excretion and/or the clinical course of NTS infections were selected. Studies reporting on adults only were not considered. Out of 532 publications which were identified during the systematic literature search, 14 publications were finally included (3273 patients in total). Quality and bias assessment was performed using the Newcastle-Ottawa scale (NOS) or the Cochrane risk-of bias tool (ROB-2). (3) Results: Four early studies from decades ago demonstrated a prolongation of intestinal NTS excretion in children after antibiotic treatment, whereas most studies published more recently observed no significant influence, which might be due to having used more "modern" antibiotic regimes ( = 7 studies). Most studies did not describe significant differences regarding the severity and duration of symptoms between untreated patients and those treated with antibiotics. Quality and bias were mainly moderate (NOS) or variable (ROB-2), respectively. (4) Conclusions: There is no substantial evidence of prolonged excretion of NTS in pediatric patients after treatment with newer antimicrobials. Consequently, clinicians should not withhold antibiotics in NTS infection for children at risk, such as for very young children, children with comorbidities, and those with suspected invasive disease due to concerns about prolonged post-convalescent bacterial excretion. In the majority of cases with uncomplicated NTS diarrhea, clinicians should refrain from applying antibiotics.

Non-Typhoidal  Infection in Children: Influence of Antibiotic Therapy on Postconvalescent Excretion and Clinical Course-A Systematic Review.

Because infections are a major driver of morbidity and mortality in children with hematologic or oncologic diseases, antimicrobials are frequently prescribed in pediatric oncology practice. However, excess or inappropriate use of antimicrobials is directly linked to the emergence of antimicrobial resistance. Although point-prevalence studies have examined the extent of antimicrobial use, a comprehensive qualitative evaluation of individual antimicrobial prescriptions remains lacking.

Antimicrobial Use in Pediatric Oncology and Hematology: Protocol for a Multicenter Point-Prevalence Study With Qualitative Expert Panel Assessment.

Clostridioides difficile Infection in Children-An Update.

Due to the high risk of severe infection among pediatric hematology and oncology patients, antimicrobial use is particularly high. With our study, we quantitatively and qualitatively evaluated, based on institutional standards and national guidelines, antimicrobial usage by employing a point-prevalence survey with a multi-step, expert panel approach. We analyzed reasons for inappropriate antimicrobial usage.

Antimicrobial use in pediatric oncology and hematology in Germany and Austria, 2020/2021: a cross-sectional, multi-center point-prevalence study with a multi-step qualitative adjudication process.

The human choroid plexus (CP) is the location of the blood-cerebrospinal fluid (CSF) barrier (BCSFB). Whereas the epithelial cells of the CP mainly contribute to the formation of the BCSFB, the vessels of the CP are built by fenestrated endothelial cells. Still, the CP endothelium can contribute to barrier function. By ectopic expression of human telomerase reverse transcriptase (hTERT) in primary human CP endothelial cells (HCPEnCs), we recently generated and characterized immortalized HCPEnCs (iHCPEnCs). Here, we compared primary cells of the sixth passage (HCPEnCs p6) with a lower (p20) and a higher passage (p50) of iHCPEnCs by transcriptome analysis. A high concordance of HCPEnCs and both passages of iHCPEnCs was observed, as only small proportions of the transcripts examined were significantly altered. Differentially expressed genes (DEGs) were identified and assigned to potentially affected biological processes by gene set enrichment analysis (GSEA). Various components of the endothelial barrier-relevant Wnt signaling were detected in HCPEnCs and iHCPEnCs. Functional analysis of HCPEnCs and iHCPEnCs showed equal marginal activation of Wnt signaling, supporting the downregulation of β-catenin (CTNNB) signaling in CP endothelial cells, and a contribution to the barrier function by the CP endothelium was retained until passage 100 (p100) of iHCPEnCs. Overall, our data support the suitability of iHCPEnCs as an in vitro model of the CP endothelium over extended passages.

Transcriptome and Functional Comparison of Primary and Immortalized Endothelial Cells of the Human Choroid Plexus at the Blood-Cerebrospinal Fluid Barrier.

Article	Year
Candidiasis caused by Candida kefyr in a neonate: case report. BMC infectious diseases\| PubMed ID: 22424058	2012
The role of prebiotics and probiotics in prevention and treatment of childhood infectious diseases. The Pediatric infectious disease journal\| PubMed ID: 22801095	2012
Bioengineered 2'-fucosyllactose and 3-fucosyllactose inhibit the adhesion of Pseudomonas aeruginosa and enteric pathogens to human intestinal and respiratory cell lines. Nutrition research (New York, N.Y.)\| PubMed ID: 24074741	2013
Anaphylaxis After Immunization of Children and Adolescents in Germany. The Pediatric infectious disease journal\| PubMed ID: 26835973	2016
Prevalence of Multidrug-Resistant Organisms in Hospitalized Pediatric Refugees in an University Children's Hospital in Germany 2015-2016. Infection control and hospital epidemiology\| PubMed ID: 27523304	2016
Expert panel diagnosis demonstrated high reproducibility as reference standard in infectious diseases. Journal of clinical epidemiology\| PubMed ID: 30930247	2019
A 28-Day-Old Boy with Multifocal Osteomyelitis Mimicking Non-Accidental Injury. Klinische Padiatrie\| PubMed ID: 32767295	2021
Emergence of Macrolide-Resistant during an Outbreak in a Primary School: Clinical Characterization of Hospitalized Children. Pathogens (Basel, Switzerland)\| PubMed ID: 33802078	2021
Non-Typhoidal Infection in Children: Influence of Antibiotic Therapy on Postconvalescent Excretion and Clinical Course-A Systematic Review. Antibiotics (Basel, Switzerland)\| PubMed ID: 34680768	2021
Antimicrobial Use in Pediatric Oncology and Hematology: Protocol for a Multicenter Point-Prevalence Study With Qualitative Expert Panel Assessment. JMIR research protocols\| PubMed ID: 35723906	2022
Clostridioides difficile Infection in Children-An Update. The Pediatric infectious disease journal\| PubMed ID: 36102737	2023
Antimicrobial use in pediatric oncology and hematology in Germany and Austria, 2020/2021: a cross-sectional, multi-center point-prevalence study with a multi-step qualitative adjudication pr... The Lancet regional health. Europe\| PubMed ID: 37180743	2023
Transcriptome and Functional Comparison of Primary and Immortalized Endothelial Cells of the Human Choroid Plexus at the Blood-Cerebrospinal Fluid Barrier. International journal of molecular sciences\| PubMed ID: 40004242	2025

Stefan Weichert

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