Christiane Sokollik

Nocturnal Arterial Oxygen Saturation and Academic Performance in a Community Sample of Children

Objective. Hypoxemia, often assessed via pulse oximetry, is associated with neurocognitive deficits in children. The best way to qualify hypoxemia, or which level of hypoxemia already affects cognition, is unknown. Methods. We assessed the association of pulse oximetry-derived variables that qualify hypoxemia with impaired academic performance in mathematics in a population-based cross-section of 995 primary school children who underwent overnight home recordings of motion-resistant new-generation pulse oximeter saturation (Spo2). Impaired academic performance in mathematics was based on the last school report and defined as grade 4 to 6 on a 6-point scale (ie, approximately the lowest quintile grades). Results. Of 10 variables under study, only the nadir of the Spo2 values was significantly associated with impaired performance. Categories of this variable representing mild (ie, 91%–93% Spo2; odds ratio: 1.65; 95% confidence interval: 1.06–2.56) and moderate hypoxemia (ie, ≤90% Spo2; odds ratio: 2.28; 95% confidence interval: 1.30–4.01) both were associated with impaired performance in mathematics. Conclusions. We suggest using the nadir of the Spo2 values in an overnight study to qualify hypoxemia in future studies. This variable may predict neurocognitive deficits in school children. Mild hypoxemia, as yet widely considered benign, may already affect cognition in childhood.

Reference values for pulse oximetry recordings in healthy term neonates during their first 5 days of life

Objective To determine reference values for pulse oximeter saturation (SpO2) variables and desaturation event indices in healthy term neonates during their first 5 days of life, and to compare two definitions for the identification of desaturation events. Design Observational study (case series). Setting Maternity ward, Department of Neonatology, University Childrens Hospital, Tuebingen, Germany. Patients 209 healthy term neonates (50% boys), median (minimum–maximum) age 2 (0–5) days. Main outcome measures SpO2 variables (eg, median SpO2) and desaturation events obtained by motion-resistant pulse oximetry (VitaGuard 310; Getemed, incorporating Masimo SET). Desaturation events were identified based either on a good signal quality (SIQ) provided by the device or on the combination of a good SIQ and an undisturbed pulse waveform (SIQ+PW). Desaturation event indices were calculated as desaturation events divided by hour of artefact-free recording time. Results The mean (SD) of the obtained median SpO2 was 97.3% (1.4%). There were 36 (17%) subjects with desaturation events to <80% SpO2 based on SIQ, and 26 (12%) based on SIQ+PW. Median desaturation event rate to <80% SpO2/h (75th centile; 95th centile; maximum) was 0 (0; 0.6; 2.3) based on SIQ, and 0 (0; 0.4; 1.7) based on SIQ+PW. Conclusions Desaturation events to <80% SpO2 were rare in our sample of healthy term neonates during their first 5 days of life. Analysis of SIQ alone could be a quick and simple alternative to traditional analysis of PW. The presented reference values may be used for clinical decision making.

Risk factors and consequences of excessive autonomic activation during sleep in children

PurposeThe aim of this study was to assess risk factors for excessive autonomic activation during sleep (EAAS) and its association with sleep problems, impaired behavior, and poor academic performance in primary school children.MethodsData from a community-based study on 997 primary school children were used. Based on nocturnal home pulse oximetry, autonomic activation during sleep was defined as a pulse rate increase by more than 20%. Children with ≥35.9 autonomic activations per hour (i.e., ≥the 95th centile) were classified as suffering from EAAS and compared with controls. Sleep problems, impaired behavior, and academic performance were assessed by parental questionnaires and analysis of school reports.ResultsAccording to the abovementioned definition, EAAS was diagnosed in 52 children (67% male). Risk factors for EAAS were male gender (odds ratio [95% confidence interval]: 2.06 [1.14–3.72]) and presence of symptoms of sleep-disordered breathing (3.48 [1.29–9.43]). Children with EAAS had a higher prevalence of hyperactive behavior (39.2% vs. 26.0%; p = 0.05) and enuresis (5.8% vs. 0.8%; p = 0.017) but not of poor academic performance. The association with hyperactive behavior was confirmed in a subsample (n = 119) using the Strengths and Difficulties Questionnaire. Mean (SD) score of the hyperactive–inattentive scale was 4.5 (2.8) for EAAS and 3.4 (2.7) for non-EAAS (p = 0.04).ConclusionEAAS may be a marker of sleep disruption in children and may predict the occurrence of enuresis and hyperactive behavior.

Detection of respiratory events using pulse rate in children with and without obstructive sleep apnea

Oximetry is a simple but insensitive diagnostic test modality for obstructive sleep apnea (OSA) in children. Sensitivity for OSA may be enhanced if pulse rate is analyzed in conjunction with oxygen saturation. We analyzed 25 ambulatory polysomnographic recordings obtained from children with (n = 5) and without (n = 20) OSA. To assess sensitivity and specificity, pulse rate increases were determined during respiratory (i.e., apneas and hypopneas; n = 965) and non‐respiratory sleep events (i.e., body movements; n = 1,197), and contrasted to baseline fluctuations (n = 209). The absolute pulse rate increase (APRI) was the parameter that differentiated best between baseline fluctuations and sleep events (area under the receiver operating characteristic curve [AUC]: 0.88). At a cutoff value of 12 beats per minute, APRI showed a sensitivity and specificity for detecting sleep events of 0.81 each. However, AUC was lower for the differentiation between respiratory and non‐respiratory sleep events (0.77) and between central and obstructive respiratory events (0.68). In OSA cases, influencing factors for APRI following respiratory events were age, occurrence of a body movement, and severity of concomitant oxygen desaturation. We conclude that pulse rate analysis may be used to detect respiratory events in oximetry recordings in children. Pediatr Pulmonol. 2010; 45:459–468.

ROS and glutathionylation balance cytoskeletal dynamics in neutrophil extracellular trap formation.

The antimicrobial defense activity of neutrophils partly depends on their ability to form neutrophil extracellular traps (NETs), but the underlying mechanism controlling NET formation remains unclear. We demonstrate that inhibiting cytoskeletal dynamics with pharmacological agents or by genetic manipulation prevents the degranulation of neutrophils and mitochondrial DNA release required for NET formation. Wiskott-Aldrich syndrome protein–deficient neutrophils are unable to polymerize actin and exhibit a block in both degranulation and DNA release. Similarly, neutrophils with a genetic defect in NADPH oxidase fail to induce either actin and tubulin polymerization or NET formation on activation. Moreover, neutrophils deficient in glutaredoxin 1 (Grx1), an enzyme required for deglutathionylation of actin and tubulin, are unable to polymerize either cytoskeletal network and fail to degranulate or release DNA. Collectively, cytoskeletal dynamics are achieved as a balance between reactive oxygen species–regulated effects on polymerization and glutathionylation on the one hand and the Grx1-mediated deglutathionylation that is required for NET formation on the other.

Hypofibrinogenemia and liver disease: a new case of Aguadilla fibrinogen and review of the literature.

Fibrinogen storage disease (FSD) is characterized by hypofibrinogenemia and hepatic inclusions due to impaired release of mutant fibrinogen which accumulates and aggregates in the hepatocellular endoplasmic reticulum. Liver disease is variable.

Function and Ventilation of Large and Small Airways in Children and Adolescents with Inflammatory Bowel Disease.

Background:Extraintestinal manifestations are common among patients with inflammatory bowel disease (IBD), whereas pulmonary involvement is considered rare. However, chronic lung diseases begin with subclinical changes of the small airways and often originate in childhood. Pulmonary involvement, particularly of the small airways, can be assessed using novel inert gas washout tests. Methods:In this prospective, single-center study, 30 children and adolescents (mean age, 14 years; SD, ±2.6; 13 boys) with IBD (mean disease duration, 3.2 years; SD, ±2.8), and 32 healthy age-matched controls, performed nitrogen multiple-breath washout, double-tracer gas single-breath washout, and diffusion capacity for carbon monoxide. Patients with IBD additionally performed spirometry, plethysmography, and measurement of exhaled nitric oxide. Results:Patients with IBD demonstrated no abnormalities in classical lung function tests. There was no difference between active disease and remission. The lung clearance index, a very sensitive indicator for small airway function, did not differ between patients with IBD and healthy controls (mean difference [95% confidence interval] −0.01 [−0.28 to 0.25]). Specific markers for peripheral lung ventilation (Sacin and Scond) were also within the normal range (0.002 [−0.003 to 0.008] and −0.002 [−0.020 to 0.015], respectively). No association was found between measures of lung function and IBD subtype, clinical disease activity scores, laboratory values, treatment modalities, or disease duration. Conclusions:In our cohort of pediatric and adolescent patients with IBD without respiratory symptoms, there was no evidence of significant lung disease on extensive screening testing. General screening of asymptomatic patients therefore appears unnecessary and is not recommended in this population.

D-lactic Acidosis: Successful Suppression of D-lactate–Producing Lactobacillus by Probiotics

Close monitoring of the stool microbial composition via 16S ribosomal RNA sequencing in a pediatric patient with SBS and D-lactic acidosis reveals treatment-specific changes. Intestinal microbiota composition in children with short bowel syndrome (SBS) is an important factor influencing the clinical outcome. An increase of D-lactate–producing bacteria can lead to D-lactic acidosis, also referred to as D-lactate encephalopathy, with severe neurologic impairment. Antibiotic treatments for D-lactic acidosis in children with SBS offer often only short-term relief. Here, we present the case of a boy with SBS who developed recurrent episodes of D-lactic acidosis even under continuous cycling antibiotic treatment. Microbiological analyses were used to detect the presence of D-lactate–producing Lactobacillus species in the stool samples. A probiotic cocktail was introduced to alter the intestinal microbiota. During follow-up under treatment with probiotics, the patient remained stable, and there was no additional need for antibiotic therapy for more than a year. Stool composition of the patient was sequenced regularly over that period. His microbiota profile changed completely in species richness, and a clustering of species according to probiotic usage was seen. Importantly, D-lactate–producing Lactobacillus strains disappeared within a few weeks after probiotic introduction and were no longer detected in the subsequent follow-up specimens.

The Use of 5-Aminosalicylic Acid in Children and Adolescents With Inflammatory Bowel Disease

Background: In ulcerative colitis (UC) 5-aminosalicylic acid (5-ASA) is recommended as primary therapy for mild to moderate disease. Topical 5-ASA has been proven especially effective. In Crohn’s disease (CD) the evidence for a beneficial role of 5-ASA is weak. We investigated the use of topical and systemic 5-ASA therapy in children and adolescents with inflammatory bowel disease. Materials and Methods: Data of patients younger than 18 years, registered between April 2008 and December 2015 in the Swiss Inflammatory Bowel Disease Cohort, were analyzed. Results: Three hundred twenty pediatric inflammatory bowel disease patients were included; 189 with CD and 131 with UC. Over one third of UC patients [51 (39%)] received topical 5-ASA therapy and 43 (33%) received combination therapy during their disease course. UC patients with left-sided colitis or proctitis were more likely to receive topical or combination therapy as compared with patients with pancolitis (P<0.001 and <0.001, respectively). An increase in the use of topical 5-ASA therapy in UC patients was noted over time from 5% to 38%. Forty-seven percent of CD patients were treated with oral 5-ASA during their disease course. The usage was stable over time at approximately 15% to 20%. Conclusions: In recent years a very positive trend showing an increase in topical 5-ASA therapy in children and adolescents with UC has been observed. However topical therapy is still used with relative low frequency, especially in patients with a more extensive disease. Conversely, despite weak evidence supporting 5-ASA use in CD patients it has been frequently prescribed. Physicians should continue to encourage their UC patients to use topical therapy.

Physiologie der eosinophilen Granulozyten

Zusammenfassung. Eosinophile Granulozyten gehoren zu den Leukozyten und sind im Blutausstrich durch ihre pinken Granula und den brillenformigen doppelt- gelappten Kern gut identifizierbar. Sie spielen bei allergischen Erkrankungen und parasitaren Infektionen eine Rolle. Nach ihrer Aktivierung setzen sie aus ihren Granula toxische Proteine frei. Sie konnen auch mit diesen Proteinen beladene extrazellulare mitochondriale DNA-Netze zur Pathogenbekampfung auswerfen. Uber verschiedenste Mediatoren stehen sie im engen Zusammenspiel mit anderen Zellen der Immunabwehr, modulieren deren Reaktion und fordern die Gewebshomoostase. Mit zunehmendem Wissen wird mehr und mehr deutlich, dass Eosinophile nicht nur Effektorzellen sind, sondern regulatorisch an Immun-, Entwicklungs- und Heilungsprozessen beteiligt sind.