Serum proteomics reveals hemophagocytic lymphohistiocytosis-like phenotype in a subset of patients with multisystem inflammatory syndrome in children.

Children with Multisystem Inflammatory Syndrome in Children (MIS-C) can present with thrombocytopenia, which is a key feature of hemophagocytic lymphohistiocytosis (HLH). We hypothesized that thrombocytopenic MIS-C patients have more features of HLH. Clinical characteristics and routine laboratory parameters were collected from 228 MIS-C patients, of whom 85 (37%) were thrombocytopenic. Thrombocytopenic patients had increased ferritin levels; reduced leukocyte subsets; and elevated levels of ASAT and ALAT. Soluble IL-2RA was higher in thrombocytopenic children than in non-thrombocytopenic children. T-cell activation, TNF-alpha and IFN-gamma signaling markers were inversely correlated with thrombocyte levels, consistent with a more pronounced cytokine storm syndrome. Thrombocytopenia was not associated with severity of MIS-C and no pathogenic variants were identified in HLH-related genes. This suggests that thrombocytopenia in MIS-C is not a feature of a more severe disease phenotype, but the consequence of a distinct hyperinflammatory immunopathological process in a subset of children.

Prospective evaluation and follow-up of nutritional status of children hospitalized in secondary-care level hospitals: a multicentre study.

Although disease-associated undernutrition is still an important problem in hospitalized children that is often underrecognized, follow-up studies evaluating post-discharge nutritional status of children with undernutrition are lacking. The aim of this multicentre prospective observational cohort study was to assess the rate of acute undernutrition (AU) and/or having a high nutritional risk (HR) in children on admission to seven secondary-care level Dutch hospitals and to evaluate the nutritional course of AU/HR group during admission and post-discharge. STRONGkids was used to indicate HR, and AU was based on anthropometric data (z-score < -2 for weight-for-age (WFA; <1 year) or weight-for-height (WFH; ≥1 year)). In total, 1985 patients were screened for AU/HR over a 12-month period. On admission, AU was present in 9.9% of screened children and 6.2% were classified as HR; 266 (13.4%) children comprised the AU/HR group (median age 2.4 years, median length of stay 3 days). In this group, further nutritional assessment by a dietitian during hospitalization occurred in 44% of children, whereas 38% received nutritional support. At follow-up 4-8 weeks post-discharge, 101 out of orginal 266 children in the AU/HR group (38%) had available paired anthropometric measurements to re-assess nutrition status. Significant improvement of WFA/WFH compared to admission (-2.48 vs. -1.51 SD; p < 0.001) and significant decline in AU rate from admission to outpatient follow-up (69.3% vs. 35.6%; p < 0.001) were shown. In conclusion, post-discharge nutritional status of children with undernutrition and/or high nutritional risk on admission to secondary-care level pediatric wards showed significant improvement, but about one-third remained undernourished. Findings warrant the need for a tailored post-discharge nutritional follow-up.

Neonatal microbiota development and the effect of early life antibiotics are determined by two distinct settler types.

The neonatal period, during which the initial gut microbiota is acquired, is a critical phase. The healthy development of the infant's microbiome can be interrupted by external perturbations, like antibiotics, which are associated with profound effects on the gut microbiome and various disorders later in life. The aim of this study was to investigate the development of intestinal microbiota and the effect of antibiotic exposure during the first three months of life in term infants. Fecal samples were collected from healthy infants and infants who received antibiotics in the first week of life at one week, one month, and three months after birth. Microbial composition was analyzed using IS-pro and compared between antibiotics-treated and untreated infants. In total, 98 infants, divided into four groups based on feeding type and delivery mode, were analyzed. At one week of age, samples clustered into two distinct groups, which were termed "settler types", based on their Bacteroidetes abundance. Caesarean-born infants belonged to the low-Bacteroidetes settler type, but vaginally-born infants were divided between the two groups. The antibiotics effect was assessed within a subgroup of 45 infants, vaginally-born and exclusively breastfed, to minimize the effect of other confounders. Antibiotics administration resulted in lower Bacteroidetes diversity and/or a delay in Bacteroidetes colonization, which persisted for three months, and in a differential development of the microbiota. Antibiotics resulted in pronounced effects on the Bacteroidetes composition and dynamics. Finally, we hypothesize that stratification of children's cohorts based on settler types may reveal group effects that might otherwise be masked.

Wheezing and infantile colic are associated with neonatal antibiotic treatment.

BACKGROUND: Cohort studies have suggested that early-life antibiotic treatment is associated with increased risk of atopy. We determined whether antibiotic treatment already in the first week of life increases the risk of atopic and non-atopic disorders. METHODS: The INCA study is a prospective observational birth cohort study of 436 term infants, with follow-up of 1 year; 151 neonates received broad-spectrum antibiotics for suspected neonatal infection (AB+), vs a healthy untreated control group (N = 285; AB-). In the first year, parents recorded daily (non-) allergic symptoms. At 1 year, doctors' diagnoses were registered and a blood sample was taken (n = 205). RESULTS: Incidence of wheezing in the first year was higher in AB+ than AB- (41.0% vs 30.5%, P = .026; aOR 1.56 [95%CI 0.99-2.46, P = .06]). Infantile colics were more prevalent in AB+ compared to AB- (21.9% and 14.4% P = .048), and antibiotic treatment was an independent risk factor for infantile colics (aOR 1.66 (95%CI 1.00-2.77) P = .05). Allergic sensitization (Phadiatop >0.70kUA/L) showed a trend toward a higher risk in AB+ (aOR 3.26 (95%CI 0.95-11.13) P = .06). Incidence of eczema, infections, and GP visits in the first year were similar in AB+ and AB-. CONCLUSION: Antibiotic treatment in the first week of life is associated with an increased risk of wheezing and infantile colics. This study may provide a rationale for early cessation of antibiotics in neonates without proven or probable infection.

Dietary supplementation with multiple micronutrients: no beneficial effects in pediatric cystic fibrosis patients.

BACKGROUND: Cystic fibrosis (CF) patients are subjected to increased oxidative stress due to chronic pulmonary inflammation and recurrent infections. Additionally, these patients have diminished skeletal muscle performance and exercise capacity. We hypothesize that a mixture of multiple micronutrients could have beneficial effects on pulmonary function and muscle performance. METHODS: A double-blind, randomized, placebo controlled, cross-over trial with a mixture of multiple micronutrients (ML1) was performed in 22 CF patients (12.9+/-2.5 yrs) with predominantly mild lung disease. Anthropometric measures, pulmonary function, exercise performance by bicycle ergometry, muscular strength and vitamins A and E were determined. RESULTS: Analysis was performed using the paired Student t-test comparing the change in each parameter during ML1 and placebo. Plasma vitamin E and A levels increased during ML1 when compared to placebo. However, no significant difference between the effect of the ML1 or placebo was observed neither for FEV1, FVC, anthropometry, nor for the parameters for muscle performance. CONCLUSIONS: The micronutrient mixture was not superior to placebo with respect to changes in pulmonary function or muscle performance in pediatric CF patients, despite a significant increase in plasma vitamin E concentrations.

Decreased coenzyme Q10 concentration in plasma of children with cystic fibrosis.

OBJECTIVES: Coenzyme Q10 (CoQ10) is an effective lipophilic antioxidant and protects against lipid peroxidation by scavenging radicals. Patients with cystic fibrosis generally have fat malabsorption; thus, we hypothesized that overall plasma CoQ10 concentration in pediatric patients with cystic fibrosis might be diminished. Because these patients have increased oxidative stress due to chronic pulmonary inflammation, we also assumed that the oxidized form of CoQ10 might be relatively increased. PATIENTS AND METHODS: The total plasma CoQ10 levels and the oxidized and reduced form were measured by high-performance liquid chromatography in 30 children with cystic fibrosis (mean FEV1 % predicted = 88.5% +/- 18.7%) and 30 age-matched controls. RESULTS: Total plasma CoQ10 levels were significantly lower in the cystic fibrosis group as compared with the control group (0.87 +/- 0.42 micromol/L and 1.35 +/- 0.39 micromol/L, respectively; P < 0.001). When correcting for the lower serum cholesterol level in patients with cystic fibrosis, this difference remained significant: the CoQ10/cholesterol ratio (micromol/mol) was 268.8 +/- 136.7 and 334.0 +/- 102.9 in patients and controls, respectively (P < 0.05). However, the CoQ10 redox status was identical in patients and controls (86.4% +/- 7.1% and 85.4% +/- 7.3%, respectively). CONCLUSIONS: We found that the overall plasma CoQ10 concentration is lower in patients with cystic fibrosis, probably because of fat malabsorption. The CoQ10 redox status was not disturbed, indicating that CoQ10 could still be adequately regenerated in this group of patients with cystic fibrosis with mild-to-moderate pulmonary disease.

Short-term protein intake and stimulation of protein synthesis in stunted children with cystic fibrosis.

BACKGROUND: Stunted children with cystic fibrosis (CF) have less net protein anabolism than do children without CF, and the result is retarded growth in the CF patients. It is not known whether protein intake above that recommended by the Cystic Fibrosis Foundation would further stimulate whole-body protein synthesis. OBJECTIVE: We studied the effects of 3 amounts of protein intake on whole-body protein synthesis and breakdown by using isotopic infusion of [1-(13)C]valine and [(15)N(2)]urea in children with stable CF who required tube feeding. DESIGN: In 8 pediatric CF patients, we administered 3 randomly allocated isocaloric diets with normal (NP), intermediate (IP), and high (HP) amounts of protein (1.5, 3, and 5 g . kg(-1) . d(-1), respectively) by continuous drip feeding during a 4-d period at 6-wk intervals. Each patient acted as his or her own control. On the fourth day of feeding, whole-body protein synthesis and breakdown were measured. RESULTS: Protein synthesis was significantly higher in the HP group (x +/- SEM: 1.78 +/- 0.07 micromol . kg(-1) . min(-1)) than in the IP (1.57 +/- 0.08 micromol . kg(-1) . min(-1); P=0.001) and NP (1.37 +/- 0.07 micromol . kg(-1) . min(-1); P < 0.001) groups. There were no significant differences in protein breakdown. Net retention of nitrogen was significantly higher in the HP group (12.93 +/- 1.42 micromol . kg(-1) . min(-1)) than in the IP (7.61 +/- 1.40 micromol . kg(-1) . min(-1); P=0.01) and HP (2.48 +/- 0.20 micromol . kg(-1) . min(-1); P < 0.001) groups. CONCLUSION: In stunted children with CF requiring tube feeding, the highest stimulation of whole-body protein synthesis was achieved with a short-term dietary protein intake of 5 g . kg(-1) . d(-1).