Akt-dependent enhanced migratory capacity of Th17 cells from children with lupus nephritis.

Th17 cells infiltrate the kidneys of patients with lupus nephritis (LN) and are critical for the pathogenesis of this disease. In this study, we show that enhanced activity of Stat3 in CD4(+)CD45RA(-)Foxp3(-) and Foxp3(low) effector T cells from children with LN correlates with increased frequencies of IL-17-producing cells within these T cell populations. The levels of retinoic acid-related orphan receptor c and IL-17 mRNA are significantly higher in PBMCs from children with LN than in those from controls. Mammalian target of rapamycin inhibition by rapamycin reduces both Stat3 activation in effector T cells and the frequency of IL-17-producing T cells in lupus patients. Complement factor C5a slightly increases the expression of IL-17 and induces activation of Akt in anti-CD3-activated lupus effector T cells. Th17 cells from children with LN exhibit high Akt activity and enhanced migratory capacity. Inhibition of the Akt signaling pathway significantly decreases Th17 cell migration. These findings indicate that the Akt signaling pathway plays a significant role in the migratory activity of Th17 cells from children with LN and suggest that therapeutic modulation of the Akt activity may inhibit Th17 cell trafficking to sites of inflammation and thus suppress chronic inflammatory processes in children with LN.

Which treatments do children with newly diagnosed non-organic urinary incontinence receive? An analysis of 3,188 outpatient cases from Germany.

AIMS: Objectives of this study were to examine the administrative incidence of urinary incontinence in children and to assess related outpatient health services utilization in this cohort. METHODS: Data of a statutory health insurance company were analyzed and outpatients from 1 to 18 years of age with a first recorded ICD-10 code for non-organic urinary incontinence during a 1-year-period (2007) were identified. For this cohort, the prescription of desmopressin, antispasmodics, non-selective monoamine reuptake inhibitors, alarm devices, and incontinence pads in the quarter of the first diagnosis and in the following one (i.e., 6 months) was evaluated with respect to age and gender. RESULTS: 3,188 patients (59.4% male; mean age 6.8 years) matched the inclusion criteria, of whom 25.4% were under 5 years old. 7.9% were prescribed desmopressin, 7.4% received urinary antispasmodics, and 7.0% were treated with alarm devices. For 77.9% of patients, no specific incontinence-related treatments were prescribed. We found considerable differences in treatment patterns between age groups, with patients ≥ 7 years receiving desmopressin more frequently than alarm devices. Regarding gender differences, the proportion of males treated with alarm devices (prevalence ratio [PR] 1.46; 95% confidence interval [95%CI] 1.11-1.92) and at least one specific treatment (PR 1.19; 95%CI 1.04-1.35) remained statistically significantly higher, even after adjusting for age. CONCLUSIONS: In our study, we found evidence that treatment modalities only partly comply with the current guidelines for treatment of children and adolescents with non-organic urinary incontinence. Therefore, the dissemination of current guidelines remains a major educational goal.

Markers of childhood lupus nephritis indicating disease activity.

Current treatment regimens for childhood lupus nephritis (LN) are associated with significant side-effects and toxicity in vulnerable phases of growth and development. The paucity of biomarkers particularly in childhood impedes the appropriate clinical management and the development of new therapeutics. We analyzed markers of immune system (BAFF, RANTES), complement (Bb, C1q, C3d-CIC, C5a) and endothelial cell activation (sVCAM-1) in children with LN (n=22, mean age 14.8±4.7 years), nephrotic syndrome (n=13) and age-matched healthy controls (n=20) to define parameters that correlate with LN activity. Complement fragments of the alternative (Bb, p=0.0004) classical (C3d-CIC, p<0.0001) and common pathway (C5a, p<0.0001) and the levels of BAFF (p<0.0001), RANTES (p=0.0002) and sVCAM-1 (p=0.0004) were significantly higher in active compared to inactive LN. Activation of complement was associated with the occurrence of anti-C1q antibodies and reduced complement C1q. Complement-activation fragments highly correlated with the markers for immune system and endothelial cell activation. The ensemble of these parameters may be of great value in identifying early flares or remissions of childhood LN, and moreover may prove useful in the assessment of new treatments and in determining the optimization of their use.

Did the removal of the indication of nocturnal enuresis for intranasal desmopressin change prescribing practice?

PURPOSE: The indication for the treatment of primary nocturnal enuresis was removed from all intranasal preparations of desmopressin in May 2007. Objective of this study was to examine whether and how fast this regulatory decision changed prescribing in affected children. METHODS: We analyzed claims data of the Gmünder ErsatzKasse (GEK) over the years 2004-2008. All children and adolescents aged 0-18 years who received at least one out-patient diagnosis of urinary incontinence in the corresponding years were included. Our outcome of interest was the proportion of oral desmopressin and its change over time. RESULTS: A total of 6308 to 7207 children with a mean age of about 8 years were included annually (62-63% were male) and 14 746 packages of desmopressin were analysed (49.9% intranasal; 50.1% oral; 0.01% parenteral preparations). The proportion of patients using desmopressin decreased slightly from 13.9% in 2004 to 12.6% in 2008 ( p for trend = 0.0131). Between January 2004 (39.1%) and December 2006 (41.3%), the proportion of oral forms was nearly constant and doubled after that within a few months to about 80%. CONCLUSIONS: Immediately after the removal of the indication for intranasal desmopressin, an increased prescribing of tablet forms in affected children was found in Germany.

[Corona in Children: the Co-Ki Study]. / Corona bei Kindern: Die Co-Ki Studie: Relevanz von SARS-CoV-2 in der ambulanten pädiatrischen Versorgung in Deutschland.

BACKGROUND: In Germany over 80% of children and adolescents are in the ambulatory care of registered pediatricians. These have a specific perspective on the COVID-19 pandemic. METHODS: For this reason, this professional group initiated a central recording of case numbers, individual case descriptions and observations on infections and illnesses with SARS-CoV­2 (www.co-ki.de). RESULTS: So far 557 pediatricians have participated. Together they care for ca. 670,000 children. They reported 9803 children who presented as suspected cases. The pediatricians themselves had a clinical suspicion of SARS-CoV­2 infections in 3654 children. In 7707 children PCR tests were carried out using nose/throat swabs of which 198 (2.6%) were positive. In addition, 731 children were tested for SARS-CoV­2 antibodies with detection in 82 cases (11.2%). Despite initially positive PCR tests, 47 children had a negative antibody test at least 2 weeks later. Our query as to infections of adults by children yielded only one case, which a telephone enquiry revealed as unlikely. DISCUSSION: From an outpatient pediatric perspective COVID-19 is rare. There was no convincing evidence that children are a relevant source of infection for SARS-CoV­2 nor that they are relevantly at risk.

Clinical evaluation of the short-form pediatric enuresis module to assess quality of life.

AIMS: The aim of this study was to determine the psychometric properties of the German version of the Pediatric Enuresis Module to assess Quality of Life, Short Form (PEMQOL-SF) in a sample of parents of children with urinary incontinence. METHODS: The parents of 88 children (63 male, 25 female, mean age: 9.3 [SD ± 2.5, range 6-18] years) with urinary incontinence were asked to complete the PEMQOL-SF. For evaluation of convergence validity, parents and children completed the respective versions of the DCGM-10 and the PinQ questionnaire. RESULTS: Mean PEMQOL-SF scores were 72.2 [SD ± 14.1] (child impact scale) and 73.7 [SD ± 16.5] (family impact scale). The PEMQOL-SF had a Cronbach's alpha of 0.68 (child impact scale) and 0.80 (family impact scale), respectively. PEMQOL-SF child [family] impact scale scores correlated with the DCGM-10 with scores of r = 0.34 (r = 0.13; self-report version) and r = 0.63 (r = 0.48; proxy version) and with the PinQ with scores of r = -0.31 (r = -0.16; self-report version) and r = -0.63 (r = -0.54; proxy version), respectively. CONCLUSIONS: The psychometric properties of the PEMQOL-SF were good for the family impact scale, but poor for the child impact scale. In its present form, the PEMQOL-SF cannot be recommended for routine clinical use. Nevertheless, a reduction of questionnaire items could lead to better psychometric properties.

Pediatric COVID-19 case with regard to the family infection chain and the psychosocial context.

The role of children in households, spreading SARS-CoV-2, may differ from measles or influenza, and therefore, these diseases are not directly comparable to COVID-19. The psychosocial aspect of infection and quarantine for families and children suggests that fear of social stigmatization can lead to not disclosing the infection.

German version of the Pediatric Incontinence Questionnaire for urinary incontinence health related quality of life.

PURPOSE: We translated and cross-culturally adapted the English version of the Pediatric Incontinence Questionnaire, and tested the reliability and validity of the German version. MATERIALS AND METHODS: This cross-sectional study was done at 3 tertiary referral centers for childhood urinary incontinence. The self-reported and proxy English version was translated and cross-culturally adapted. From July 2007 to April 2008 we evaluated the German version in 91 boys and 54 girls with a mean +/- SD age of 9.3 +/- 2.2 years (range 6 to 18) with nonneurogenic urinary incontinence and in their parents. For concurrent criterion related validity, the German questionnaire scales were compared with those of the DCGM-10/-12. RESULTS: On reliability testing of the self-reported and proxy German versions Cronbach's alpha was 0.84 and 0.86, respectively. Interrater convergence between the self-reported and proxy versions showed an ICC of 0.81. Reproducibility was satisfactory for the self-reported and proxy versions (ICC 0.77, 95% CI 0.77-0.90 and 0.85, 95% CI 0.67-0.84, respectively). German version scores correlated with DCGM-10/-12 scores (self-report and proxy r = -0.71 and -0.69, respectively). Mean German version total scores were 23.0 in boys and 23.9 in girls. Except for a slight significant association between age and German version total score in the proxy version (p = 0.01), age, sex and incontinence type or severity (number of wet days/nights per 14 days) were not significantly associated with German version total scores. CONCLUSIONS: The German version of the Pediatric Incontinence Questionnaire is a valid and reliable outcome measure to assess health related quality of life in children and adolescents with urinary incontinence.

Urinary incontinence in children.

BACKGROUND: Urinary incontinence (bedwetting, enuresis) is the commonest urinary symptom in children and adolescents and can lead to major distress for the affected children and their parents. Physiological and non-physiological types of urinary incontinence are sometimes hard to tell apart in this age group. METHODS: This article is based on selected literature retrieved by a PubMed search and on an interdisciplinary expert consensus. RESULTS AND CONCLUSION: Nocturnal enuresis has a variety of causes. The main causative factors in monosymptomatic enuresis nocturna (MEN) are an impaired ability to wake up when the bladder is full, due to impaired or absent perception of fullness during sleep, and an imbalance between bladder capacity and nocturnal urine production. On the other hand, non-monosymptomatic enuresis nocturna (non-MEN) is usually traceable to bladder dysfunction, which is also the main cause of diurnal incontinence. A basic battery of non-invasive diagnostic tests usually suffices to determine which type of incontinence is present. Further and more specific testing is indicated if an organic cause is suspected or if the treatment fails. The mainstay of treatment is urotherapy (all non-surgical and non-pharmacological therapeutic modalities). Some patients, however, will need supportive medication in addition. Urinary incontinence has different causes in children and adults and must therefore be diagnosed and treated differently as well. All physicians who treat the affected children (not just pediatricians and family doctors, but also pediatric nephrologists, urologists, pediatric surgeons, and child psychiatrists) must be aware of the specific features of urinary incontinence in childhood.