Volatile Organic Compounds, Bacterial Airway Microbiome, Spirometry and Exercise Performance of Patients after Surgical Repair of Congenital Diaphragmatic Hernia.

The aim of this study was to analyze the exhaled volatile organic compounds (VOCs) profile, airway microbiome, lung function and exercise performance in congenital diaphragmatic hernia (CDH) patients compared to healthy age and sex-matched controls. A total of nine patients (median age 9 years, range 6-13 years) treated for CDH were included. Exhaled VOCs were measured by GC-MS. Airway microbiome was determined from deep induced sputum by 16S rRNA gene sequencing. Patients underwent conventional spirometry and exhausting bicycle spiroergometry. The exhaled VOC profile showed significantly higher levels of cyclohexane and significantly lower levels of acetone and 2-methylbutane in CDH patients. Microbiome analysis revealed no significant differences for alpha-diversity, beta-diversity and LefSe analysis. CDH patients had significantly lower relative abundances of Pasteurellales and Pasteurellaceae. CDH patients exhibited a significantly reduced Tiffeneau Index. Spiroergometry showed no significant differences. This is the first study to report the VOCs profile and airway microbiome in patients with CDH. Elevations of cyclohexane observed in the CDH group have also been reported in cases of lung cancer and pneumonia. CDH patients had no signs of impaired physical performance capacity, fueling controversial reports in the literature.

Microbial Evidence in Congenital Pulmonary Airway Malformations of Young Asymptomatic Infants.

Introduction: Experts of pediatric endosurgery recommend early thoracoscopic resection of congenital pulmonary airway malformations (CPAM) even in asymptomatic infants due to the risk of later infections. However, neither the rate of lower airway inflammation nor the underlying microbes and their pathogenic potential have been revealed in CPAMs yet. Using latest gene-sequencing techniques, we present the first study analyzing the pulmonary microbiome in young asymptomatic infants with CPAM. Materials and Methods: Seven asymptomatic infants (age 2-3 months) underwent thoracoscopic lobectomy for CPAM. Preoperatively, blood test was taken to rule out systemic infections. Surgical specimen was screened and graded for local inflammation by hematoxylin and eosin (HE) histology. The pulmonary microbiome and mycobiome were assessed using next-generation sequencing. Results: Preoperatively, all infants had normal white blood cell counts and normal C-reactive protein (CRP) levels. Microbial evidence was found in 4/7 patients, 3 being bacteria (Pseudomonas twice, Streptococcus sp. once) and 1 fungal species (Pneumocystis jirovecii, mostly known from immunosuppressed patients, and Preussia funiculata). Histologically, both Pseudomonas and fungi were associated with low and intermediate pulmonary inflammation, whereas Streptococcus was negative for leucocyte infiltration. Conclusion: For the first time ever this study revealed genetic evidence of pathogenic microbes in 4/7 CPAMs causing lower airway inflammation in 3/7 asymptomatic young infants. Especially pseudomonas and fungi represent considerable pathogenic potential and call for a broader, age-dependent, multicenter study of CPAMs. Such data could be important for pediatric surgeons counseling parents about the necessity and timing of thoracoscopic resections.

The effects of neuroblastoma and chemotherapy on metabolism, fecal microbiome, volatile organic compounds, and gut barrier function in a murine model.

BACKGROUND: Following transplantation of human neuroblastoma (NB) cells into athymic mice, we investigated the effects of tumor growth and cyclophosphamide (CTX) treatment on systemic metabolism, gut inflammation and permeability, fecal microbiome and volatile organic compounds (VOCs). METHODS: NB cells (MHH-NB11) were implanted into athymic mice (n=20); 20 healthy mice served as controls (sham).  CTX was given to 20 animals (10 NB and 10 sham) after 8 and 9 weeks. Metabolic changes were measured. Ileum samples were obtained for RT-PCR (claudins 2 and 4, occludin, tight junction protein 1) and apoptosis rate determination. Fecal microbiome and VOCs were analyzed. Values were compared to sham animals. RESULTS: NB caused reduction of adipose tissue, increases of IL-6 and TNF-α, and decreases of TGF-ß1 and -ß2. Serum FITC-dextrane levels were increased in NB and improved under CTX. Claudin 4 expression was higher in NB versus NB + CTX and sham animals. NB caused increased apoptosis of epithelial cells. NB but also CTX led to a reduction in the abundance of Lactobacillus. NB led to alterations of the fecal VOC profile. CONCLUSIONS: NB caused a catabolic pro-inflammatory state, increased gut permeability, altered fecal VOCs and reductions of Lactobacillus. Further investigations are required to determine if modifications of the intestinal microbiome may reverse some of the observed effects.

A multinational survey on the infrastructural quality of paediatric intensive care units.

BACKGROUND: The aim of the present study was to assess whether paediatric intensive care units (PICUs) in three central European countries comply with guidelines concerning infrastructure provided by the European Society of Intensive Care Medicine (ESICM). Between July 2016 and May 2017, a survey was conducted based on the ESICM guidelines. The questionnaire was structured into four categories: structural quality, diagnostic/therapeutic equipment, personnel and organization. All PICUs treating paediatric patients in the D-A-CH region [Germany (D), Austria (A) and Switzerland (CH)] were researched through the national societies. A total of 126 PICUs were contacted (D: 106; A: 12; and CH: 8). RESULTS: Eighty-five of 126 PICUs responded (D: 67%; A: 61%; and CH: 100%). A median of 500 patients was treated annually (D: 500; A: 350; and CH: 600) with a median of 12 beds (D: 12; A: 8; and CH: 12). Recommendations regarding infrastructure were met as follows: structural quality 62% in D, 71% in A and 75% in CH; diagnostic/therapeutic equipment: 87% in D, 91% in A and 89% in CH; personnel: 65% in D, 87% in A and 85% in CH; and organization: 75% in D, 73% in A and 88% in CH. CONCLUSIONS: This survey reveals deficits concerning structural quality in all countries. Furthermore, shortcomings regarding personnel were found in Germany and for organization in Germany and Austria. These issues need to be addressed urgently to further improve treatment quality and patient safety in the future.

The diagnostic value of hepcidin to predict the presence and severity of appendicitis in children.

BACKGROUND: The aim of this study was to determine the diagnostic capacity of hepcidin in pediatric acute appendicitis and its accuracy as a predictor of the severity of appendicitis. MATERIALS AND METHODS: In children with appendicitis (n = 39), leukocytes, platelet count, and the serum levels of C-reactive protein (CRP) and hepcidin were compared to a control group (n = 25) of patients with unspecific abdominal pain. Additionally, parameters were compared between children with simple (n = 17) and complicated appendicitis (n = 22). Receiver operation characteristic analyses of the different parameters were performed and the areas under the curve (AUCs) calculated. RESULTS: Leukocytes and serum hepcidin levels were significantly higher in children with acute appendicitis versus control group (13.7 ± 5.7 versus 9.8 ± 3.9 G/L, P = 0.005 and 31.3 ± 21.7 versus 20.4 ± 14 ng/mL, P = 0.039). AUCs for hepcidin, leukocytes, and CRP were 0.654, 0.711, and 0.619, respectively. Complicated appendicitis was associated with significantly higher hepcidin concentrations compared to simple appendicitis (38.5 ± 17.6 ng/mL versus 21.6 ± 23.4 ng/mL, P < 0.001). A combination of leukocytes, CRP, and hepcidin had the highest AUC (0.914) to predict complicated appendicitis. CONCLUSIONS: Increased serum levels of hepcidin were found in children with appendicitis compared to controls. While hepcidin was useful to identify patients with complicated appendicitis as it does not seem appropriate to distinguish between simple appendicitis and other causes for acute abdominal pain.

Cardiovascular risk and mineral bone disorder in patients with chronic kidney disease.

The term chronic kidney disease-mineral bone disorder has been coined recently to highlight that the disturbed mineral and bone metabolism is a major contributor to vascular calcification and finally cardiovascular disease. This syndrome is characterized by clinical, biochemical and/or histological findings, i.e. i) biochemical alterations in the homeostasis of calcium, phosphate and their key player parathyroid hormone (PTH), Fibroblast growth factor-23 (FGF-23), klotho and vitamin-D, ii) the occurrence of vascular and/or soft tissue calcification, and iii) an abnormal bone structure and/or turnover. Apart from the combined and synergistic action of "traditional" and uremia-related risk factors, promoters and inhibitors of calcification have to be considered as well. This review will focus on the disturbed mineral metabolism as the triggering force behind distortion of vascular integrity and cardiovascular malfunction in CKD patients.