Development of a Novel Prediction Tool for Response to First-Line Treatments of Monosymptomatic Nocturnal Enuresis: A Randomized, Controlled, International, Multicenter Study (DRYCHILD).

PURPOSE: Nocturnal urine volume and bladder reservoir function are key pathogenic factors behind monosymptomatic nocturnal enuresis (MNE). We investigated the predictive value of these together with other demographic and clinical variables for response to first-line treatments in children with MNE. MATERIALS AND METHODS: A randomized, controlled, international, multicenter study was conducted in 324 treatment-naïve children (6-14 years old) with primary MNE. The children were randomized to treatment with or without prior consideration of voiding diaries. In the group where treatment choice was based on voiding diaries, children with nocturnal polyuria and normal maximum voided volume (MVV) received desmopressin (dDAVP) treatment, and children with reduced MVV and no nocturnal polyuria received an enuresis alarm. In the other group, treatment with dDAVP or alarm was randomly allocated. RESULTS: A total of 281 children (72% males) were qualified for statistical analysis. The change of responding to treatment was 21% higher in children where treatment was individualized compared to children where treatment was randomly selected (risk ratio = 1.21 [1.02-1.45], P = .032). In children with reduced MVV and no nocturnal polyuria (35% of all children), individualized treatment was associated with a 46% improvement in response compared to random treatment selection (risk ratio = 1.46 [1.14-1.87], P = .003). Furthermore, we developed a clinically relevant prediction model for response to dDAVP treatment (receiver operating characteristic curve 0.85). CONCLUSIONS: The present study demonstrates that treatment selection based on voiding diaries improves response to first-line treatment, particularly in specific subtypes. Information from voiding diaries together with clinical and demographic information provides the basis for predicting response. CLINICAL TRIAL REGISTRATION NO.: NCT03389412.

A comparison of the breast milk microbiota from women diagnosed with gestational diabetes mellitus and women without gestational diabetes mellitus.

BACKGROUND: Human breast milk (HBM) is a contributing factor in modulating the infant's gut microbiota, as it contains bacteria that are directly transferred to the infant during breastfeeding. It has been shown that children of women diagnosed with gestational diabetes mellitus (GDM) have a different gut microbiota compared to children of women without GDM. Our hypothesis is therefore that women with GDM have a different HBM microbiota, which may influence the metabolic function and capacity of the child later in life. The aim of this study was to investigate whether women with GDM have a different breast milk microbiota 1-3 weeks postpartum compared to women without GDM. METHODS: In this case-control study, a total of 45 women were included: 18 women with GDM and 27 women without GDM. A milk sample was collected from each participant 1 to 3 weeks postpartum and the bacterial composition was examined by 16 S rRNA gene sequencing targeting the V4 region. RESULTS: High relative abundances of Streptococcus and Staphylococcus were present in samples from both women with and without GDM. No difference could be seen in either alpha diversity, beta diversity, or specific taxa between groups. CONCLUSION: Our results did not support the existence of a GDM-associated breast milk microbiota at 1-3 weeks postpartum. Further research is needed to fully understand the development of the gut microbiota of infants born to mothers with GDM.

Musculoskeletal misdiagnoses in pediatric patients with spinal tumors.

OBJECTIVE: Childhood spinal tumors often present with musculoskeletal symptoms, potentially causing a misdiagnosis and delays in diagnosis and treatment. This study aims to identify, characterize, and compare children with spinal tumors who had prior musculoskeletal misdiagnoses to those without, analyzing clinical presentation, diagnostic interval, and outcome. STUDY DESIGN: This retrospective cohort study evaluated all children aged 0-14 years diagnosed with a spinal tumor in Denmark from 1996 to 2018. The cohort was identified through the Danish Childhood Cancer Registry, and the registry data were supplemented with data from medical records. The survival was compared using the Kaplan-Meier method. RESULTS: Among 58 patients, 57% (33/58) received musculoskeletal misdiagnoses before the spinal tumor diagnosis. Misdiagnoses were mostly nonspecific (64%, 21/33), involving pain and accidental lesions, while 36% (12/33) were rheumatologic diagnoses. The patients with prior misdiagnosis had less aggressive tumors, fewer neurological/general symptoms, and 5.5 months median diagnostic interval versus 3 months for those without a misdiagnosis. Those with prior misdiagnoses tended to have a higher 5-year survival of 83% (95% confidence interval [CI]: 63%-92%) compared to 66% (95% CI: 44%-82%) for those without (p = .15). CONCLUSION: Less aggressive spinal tumors may manifest as gradual skeletal abnormalities and musculoskeletal symptoms without neurological/general symptoms, leading to misdiagnoses and delays.

Discontinuing absorbent pants in children with bedwetting: a randomized controlled trial.

The objective of this study is to examine the effect of discontinuing wearing protective garments (absorbent pyjama pants - APP) in children with severe childhood nocturnal enuresis (NE). The study employs a multicenter, parallel, randomized controlled trial. Following a 4-week run-in period, participants were randomly allocated in a 2:1 group allocation to discontinue or continue using APP. The research was conducted across seven European pediatric incontinence centers. The study included treatment-naïve children aged 4-8 years with severe (7/7 wet nights per week) mono-symptomatic NE, who had used nighttime protection for at least 6 months prior to the study. The study consisted of a 4-week run-in period (± 7 days), where all children slept wearing APP (DryNites®). At week 4 (± 7 days), if meeting randomization criteria (7/7 wet nights during the last week of run-in), participants were randomized to continue to sleep in APP or to discontinue their use for a further 4 weeks, with the option of another 4 weeks in the extension period. The primary outcome was the difference between groups of wet nights during the last week of intervention. Quality of life (QoL) and sleep were secondary endpoints. In total, 105 children (43 girls and 62 boys, mean age 5.6 years [SD 1.13]) were randomized (no-pants group n = 70, pants group n = 35). Fifteen children (21%) in the no-pants group discontinued early due to stress related to the intervention. Children in the no-pants group experienced fewer wet nights compared to the pants group during the last week (difference 2.3 nights, 95% CI 1.54-3.08; p < 0.0001). In the no-pants group, 20% responded to the intervention, of whom 13% had a full response. Clinical improvement was detected within 2 weeks. Sleep and QoL were reported as negatively affected by APP discontinuation in the extension period but not in the core period.    Conclusion: A ~ 10% complete resolution rate was associated with discontinuing APP. While statistically significant, the clinical relevance is debatable, and the intervention should be tried only if the family is motivated. Response was detectable within 2 weeks. Discontinuing APP for 4-8 weeks was reported to negatively affect QoL and sleep quality. No severe side effects were seen.Trial registration: Clinicaltrials.gov Identifier: NCT04620356; date registered: September 23, 2020. Registered under the name: "Effect of Use of DryNites Absorbent Pyjama Pants on the Rate of Spontaneous Resolution of Paediatric Nocturnal Enuresis (NE)."

Diabetic ketoacidosis and severe hypertriglyceridaemia in a child.

Diabetic ketoacidosis (DKA) in children with severe hypertriglyceridaemia (S-HTG) is infrequent. This case report presents a seven-year-old girl without a family history of dyslipidaemia with moderate DKA, lipaemic plasma, retinal lipaemia, and P-triglyceride 185 mmol/l. The course was uneventful on standard treatment and lipids normalized. She had abdominal pain but no biochemical or ultrasound evidence of pancreatitis. S-HTG affected laboratory analysis; CO2 could not be analyzed, and there was haemolysis and uncertain electrolyte results with P-Na+ 125 mmol/l, i.e. pseudo hyponatraemia, despite ultracentrifugation.

GFR measurements and ultrasound findings in 154 children with a congenital solitary functioning kidney.

BACKGROUND: Multicystic dysplastic kidney (MCDK) and unilateral renal agenesis (URA) are the most common reasons for a congenital solitary functioning kidney (SFK). We aimed to assess the presence of abnormalities in the congenital SFK and evaluate kidney function using chrome EDTA (CrEDTA) measurements. METHODS: We retrospectively reviewed the medical records of 154 children with MCDK and URA in the period from 2005 to 2022 to analyze results from ultrasound scans and CrEDTA glomerular filtration rate (GFR) examinations. RESULTS: Of 154 children with a solitary kidney due to MCDK (62%) or URA (38%), abnormalities on the congenital SFK were found in 13 children (8%). The abnormalities spontaneously resolved in 6 children (46%). The most common abnormality was hydronephrosis. Compensatory hypertrophy was found in 17% of the children within the first 6 months of life. 116 children (90%) had a standard GFR (sdGFR) above 75% of expected for the age. Out of those with a sdGFR below 75% of expected, 3 (23%) had abnormalities in the congenital SFK. There was no difference in sdGFR between children with MCDK and URA. CONCLUSIONS: Our study is the first using CrEDTA for GFR measurements and suggests that most children with a congenital SFK due to MCDK or URA have a kidney function within expected for the age. Compensatory hypertrophy of the SFK is found in a minority of children within the first six months of life, suggesting that this process is developing over time. The prevalence of abnormalities in the SFK seems low, however those with abnormalities (e.g. hydronephrosis) are at higher risk of reduced sdGFR.

Musculoskeletal misdiagnoses in children with brain tumors: A nationwide, multicenter case-control study.

OBJECTIVE: Childhood brain tumors belong to the cancer type with the longest diagnostic delay, the highest health care utilization prior to diagnosis, and the highest burden of long-term sequelae. We aimed to clarify whether prior musculoskeletal diagnoses in childhood brain cancer were misdiagnoses and whether it affected the diagnostic delay. STUDY DESIGN: In this retrospective, chart-reviewed case-control study we compared 28 children with brain tumors and a prior musculoskeletal diagnosis to a sex and age-matched control group of 56 children with brain tumors and no prior musculoskeletal diagnosis. Using the Danish registries, the cases were identified from consecutive cases of childhood brain cancers in Denmark over 23 years (1996-2018). RESULTS: Of 931 children with brain tumors, 3% (28/931) had a prior musculoskeletal diagnosis, of which 39% (11/28) were misdiagnoses. The misdiagnoses primarily included torticollis-related diagnoses which tended to a longer time interval from first hospital contact until a specialist was involved: 35 days (IQR 6-166 days) compared to 3 days (IQR 1-48 days), p = 0.07. When comparing the 28 children with a prior musculoskeletal diagnosis with a matched control group without a prior musculoskeletal diagnosis, we found no difference in the non-musculoskeletal clinical presentation, the diagnostic time interval, or survival. Infratentorial tumor location was associated with a seven-fold risk of musculoskeletal misdiagnosis compared to supratentorial tumor location. CONCLUSION: Musculoskeletal misdiagnoses were rare in children with brain tumors and had no significant association to the diagnostic time interval or survival. The misdiagnoses consisted primarily of torticollis- or otherwise neck-related diagnoses.

Children and adolescents with attention deficit hyperactivity disorder and autism spectrum disorder share distinct microbiota compositions.

An association has been suggested between altered gut microbiota, and attention deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD), respectively. Thus, we analyzed the gut microbiota composition in children and adolescents with or without these disorders and evaluated the systemic effects of these bacteria. We recruited study participants diagnosed with ADHD, ASD, and comorbid ADHD/ASD, while the control groups consisted both of siblings and non-related children. The gut microbiota was analyzed by 16S rRNA gene sequencing of the V4 region, while the concentration of lipopolysaccharide-binding protein (LBP), cytokines, and other signaling molecules were measured in plasma. Importantly the gut microbiota compositions of cases with ADHD and ASD were highly similar for both alpha- and beta-diversity while differing from that of non-related controls. Furthermore, a subset of ADHD and ASD cases had an increased LBP concentration compared to non-affected children, which was positively correlated with interleukin (IL)-8, 12, and 13. These observations indicate disruption of the intestinal barrier and immune dysregulation among the subset of children with ADHD or ASD.

Phagocyte-related S100 proteins and cytokines in acute lymphoblastic leukemia and their prognostic value.

In this retrospective cohort study, we evaluated the level of biomarkers of inflammation like phagocyte-related S100 proteins and a panel of cytokines in 128 children with pre-B ALL and 22 with T-ALL. The biomarkers were evaluated at diagnosis and during antileukemic therapy (day 29 and after six months) and we evaluated their correlation with basic laboratory values. Further, for the children with pre-B ALL, we evaluated whether the biomarkers could predict the outcome of ALL expressed as minimal residual disease (MRD), relapse, and death.The levels of S100A9, S100A12, IL-1beta, IL-12p70, IL-13, IL-17, IL-18, and MPO serum levels increased significantly as chemotherapy was initiated. The difference was most pronounced for S100A9 and S100A12, which had strong positive correlations with the neutrophil counts. In contrast, TNF-alpha, IL-6, IL-10, CCL-2, MMP-3, and CD25 serum levels decreased after chemotherapy. Although none of these biomarkers appear to be an independent predictor of outcomes, in predictive models with MRD as the outcome, AUC increased from 76% (95% CI 68-84%) when using initial risk group stratification alone to 83% (95% CI 73-91%) in a multivariate predictive model including initial risk group stratification and the biomarkers S100A12, TNF-alpha, and IL-10.

Food addiction is strongly associated with type 2 diabetes.

BACKGROUND & AIMS: Individuals can develop an addiction-like attraction towards highly processed foods, which has led to the conceptualization of food addiction, a phenotype linked to obesity. In this study, we investigated whether food addiction is associated with type 2 diabetes (T2D). METHODS: 1699 adults from the general population and 1394 adults from a population with clinically verified mental disorder completed a cross-sectional survey including the Yale Food Addiction Scale 2.0. Logistic regression was employed to examine the association between food addiction and T2D, the latter operationalized via Danish registers. RESULTS: Food addiction was strongly associated with T2D in the general population (adjusted odds ratio (AOR) = 6.7) and among individuals with mental disorder (AOR = 2.4) in a dose-response-like manner. CONCLUSION: This is the first study to demonstrate a positive association between food addiction and T2D in a general population sample. Food addiction may be a promising target for prevention of T2D.

Functional constipation as a risk factor for pyelonephritis and recurrent urinary tract infection in children.

AIM: Acute pyelonephritis is one of the most common bacterial infections in childhood. This potentially serious condition can lead to renal scarring, loss of kidney function and hypertension. The aim of this study was to identify risk factors associated with pyelonephritis in children without kidney or urinary tract abnormalities. METHODS: Medical records of children aged 4-18 diagnosed with 1st time pyelonephritis from 2016 to 2021 were retrospectively analysed. Children with abnormal kidney ultrasound were excluded. In addition to demographic data, information on bladder and bowel function was extracted together with habits of fluid intake. RESULTS: A total of 105 patients were diagnosed with 1st time pyelonephritis. Of these, 47% were diagnosed with constipation according to the Rome IV criteria within a mean follow-up period of 167 days after their pyelonephritis, which is markedly higher than the estimated prevalence of constipation in the background population. Constipation was positively associated with recurrent urinary tract infection (p = 0.01). CONCLUSION: Constipation is associated with pyelonephritis and recurrent urinary tract infection in children (primarily girls) 4-18 years of age without evident kidney or urinary tract abnormalities. We recommend systematic evaluation of bowel and bladder function after 1st time pyelonephritis in all children >4 years.

Renal scars in children with febrile urinary tract infection - Looking for associated factors.

INTRODUCTION: Febrile urinary tract infection (UTI) is a common childhood infection related to renal scarring and potentially long-term complications like chronic kidney disease. It would be of great benefit to find a correlation between easy-accessible factors in the acute phase of a febrile UTI and the development of renal scar formation and/or decreased renal function in order to identify children at risk of future complications. OBJECTIVE: The aim of this study was to identify factors associated with the development of decreased split renal function (DSRF) and/or permanent renal scar formation in children with febrile UTI. STUDY DESIGN: The medical records of 212 Children aged 0 months to 15 years with febrile UTI admitted to The Pediatric Department of Lillebaelt Hospital, Kolding from January 2011 to September 2014 were systematically reviewed. We analyzed clinical, laboratory, and radiologic findings. Statistical analysis was performed to identify factors associated with renal scar formation and DSRF on nuclear imaging at 6 months follow-up. RESULTS: A total of 113 medical records were eligible for further analysis, 99 girls and 14 boys, 34 patients younger than 12 months. In total 30 patients (26.5%) had an abnormal follow-up imaging (DSRF less than 45% and/or renal scarring). Nine patients (8%) had renal scarring. Four patients (3.5%) had renal scarring only, 21 patients (18.6%) had DSRF only, and five patients (4.4%) had both renal scarring and DSRF. Patients with renal scar formation on follow-up imaging had significantly higher C-reactive protein (CRP) than patients with no scarring (p < 0.01). CRP and absolute neutrophil count (ANC) was significantly higher in patients with abnormal follow-up imaging (p < 0.01 and p = 0.010), and these patients more often had positive nitrite in urine dipstick compared to patients with normal kidneys on follow-up (p = 0.048). Temperature above 38.5 °C and CRP >50 mg/L in combination were also associated with a higher risk of abnormal follow-up imaging (p = 0.016). DISCUSSION: This study contributes with further knowledge to the ongoing debate regarding renal scarring but also reveals the possibility of associated factors for the development of DSRF following a febrile UTI in children. However, due to the retrospective design as well as the small number of events in our study definite conclusions on whether the above-mentioned factors are indeed prognostic for the development of renal scarring or DSRF following a febrile UTI can not be drawn.

The chance of spontaneous patent ductus arteriosus closure in preterm infants born before 32 weeks of gestation is high and continues to increase until 5 years of follow-up.

AIM: The primary aim was to estimate premature infants' spontaneous patent ductus arteriosus closure rate. Secondly, to identify criteria associated with the chance of spontaneous closure. METHODS: We performed a retrospective cohort study of 167 infants born before 32 weeks of gestation and diagnosed with a patent ductus arteriosus between 1 January 2008 and 31 December 2017. The spontaneous patent ductus arteriosus closure event rate was evaluated using the Kaplan-Meier estimator. RESULTS: The spontaneous closure rate within the first year of life was 66% (95% CI 58%-73%), increasing to 80% (95% CI 72%-86%) five years after birth. When including both spontaneous closure and closure following treatment, 96% (95% CI 86%-100%) closed within 5 years after birth. The chance of spontaneous closure was reduced in the case of a large patent ductus arteriosus: OR 0.16 (95% CI 0.05-0.52), left atrial enlargement: OR 0.16 (95% CI 0.05-0.51), and pulmonary hypertension: OR 0.23 (95% CI 0.07-0.74). CONCLUSION: The chance of spontaneous closure in premature infants born between 23 and 32 weeks of gestation was high, and the incidence continued increasing until 5 years of follow-up.

The incidence of eosinophilic oesophagitis in 2007-2017 among children in North Denmark Region is lower than expected.

BACKGROUND: In North Denmark Region (NDR), the incidence of Eosinophilic Oesophagitis (EoE) among adults has increased following a new biopsy protocol in 2011, whereas data on the incidence of EoE among children is lacking. AIMS: To describe the incidence of EoE in children aged 0-17 in NDR as well as diagnostic delay, clinical manifestations, treatment and complications. METHODS: This retrospective, register-based DanEoE cohort study included 18 children diagnosed with EoE between 2007-2017 in NDR. Medical files were reviewed with attention to symptoms, reason for referral, disease progress, treatment, symptomatic and histological remission as well as diagnostic delay. RESULTS: The median incidence per year (2007-2017) was 0.86/100,000 children in NDR aged 0-17 years. The median diagnostic delay among children was four years and six months. Sixty percent presented with food impaction at first hospital visit. After initial treatment, only one of 18 children achieved symptomatic and histologic remission and had a long-term treatment plan. CONCLUSIONS: The calculated incidence among children was lower compared to similar studies. Combined with poor remission rates and lack of follow-up, it is likely that EoE is an underdiagnosed and insufficiently treated disease among children in NDR. Our findings suggest that more knowledge concerning EoE in children could lead to a higher incidence, shorter diagnostic delay and more effective treatment.

[Tubulointerstitial nephritis and uveitis syndrome].

Tubulointerstitial nephritis and uveitis (TINU) syndrome in children is an uncommon, underreported condition. Onset of renal and ocular symptoms is often not simultaneous with nephritis which may precede uveitis by several months. A variable treatment response and a propensity for relapse characterize the syndrome. This is a case report of a previously healthy 14-year-old boy with TINU syndrome, emphasizing the need for long-term interdisciplinary treatment and monitoring. Also, the importance of repetitive screening of patients with uveitis for renal disease and ophthalmological evaluation of children with nephritis is emphasized.

Characteristics of the gut microbiome in women with gestational diabetes mellitus: A systematic review.

BACKGROUND: The incidence of women developing gestational diabetes mellitus (GDM) is increasing, which is associated with an increased risk of type 2 diabetes mellitus (T2DM) for both mother and child. Gut microbiota dysbiosis may contribute to the pathogenesis of both GDM and the accompanying risk of T2DM. Thus, a better understanding of the microbial communities associated with GDM could offer a potential target for intervention and treatment in the future. Therefore, we performed a systematic review to investigate if the GDM women have a distinct gut microbiota composition compared to non-GDM women. METHODS: We identified 21 studies in a systematic literature search of Embase and PubMed up to February 24, 2021. Data on demographics, methodology and identified microbial metrics were extracted. The quality of each study was assessed according to the Newcastle-Ottawa Scale. RESULTS: Sixteen of the studies did find a GDM-associated gut microbiota, although no consistency could be seen. Only Collinsella and Blautia showed a tendency to be increased in GDM women, whereas the remaining genera were significantly different in opposing directions. CONCLUSION: Although most of the studies found an association between GDM and gut microbiota dysbiosis, no overall GDM-specific gut microbiota could be identified. All studies in the second trimester found a difference between GDM and non-GDM women, indicating that dysbiosis is present at the time of diagnosis. Nevertheless, it is still unclear when the dysbiosis develops, as no consensus could be seen between the studies investigating the gut microbiota in the first trimester of pregnancy. However, studies varied widely concerning methodology and study design, which might explain the highly heterogeneous gut microbiota compositions between studies. Therefore, future studies need to include multiple time points and consider possible confounding factors such as ethnicity, pre-pregnancy body mass index, and GDM treatment.

Transcutaneous electrical nerve stimulation as add-on therapy in children receiving anticholinergics and/or mirabegron for refractory daytime urinary incontinence: A retrospective cohort study.

AIMS: To investigate if children with daytime urinary incontinence (DUI) and overactive bladder (OAB) refractory to standard urotherapy and medicinal treatment, would experience improvement in symptoms after add-on treatment with transcutaneous electrical nerve stimulation (TENS). METHODS: Children were retrospectively enrolled from tertiary referral centers at Aarhus and Aalborg University Hospitals. All data were retrieved from the patients' journals. All children were prescribed TENS as an add-on treatment to the highest-tolerable dose of medicinal treatment in a standardized regime of 2 h a day for around 3 months. Primary endpoints were the number of wet days per week (WDPW) and incontinence episodes per day. Effect of treatment was defined as greater or equal to 50% reduction in the frequency of DUI episodes. Secondary endpoints were to establish predictive factors for the effect of treatment using logistic regression. RESULTS: Seventy-six children diagnosed with DUI and OAB refractory to treatment with standard urotherapy and pharmacological treatment, at the age of 5-16 years were included from February 2017 to February 2020. A reduction in WDPW (from 6.31 [5.86-6.61] to 4.27 [3.45-4.90], p < 0.05) and incontinence episodes per day (from 2.45 [1.98-2.91] to 1.43 [1.07-1.80], p < 0.05) was observed. Twelve patients became completely dry. At 6 months follow-up, seven of the 12 complete responders had relapsed while five remained dry. A history of constipation before TENS was a predictor of poor treatment response (p = 0.016). CONCLUSIONS: TENS as add-on to anticholinergic treatment seems effective in a number of children with treatment-refractory DUI.

Musculoskeletal Diagnoses before Cancer in Children: A Danish Registry-Based Cohort Study.

OBJECTIVE: To identify the prevalence of musculoskeletal diagnoses recorded 6 months before the diagnosis of cancer and to evaluate whether preceding musculoskeletal diagnoses affected survival. STUDY DESIGN: We performed a nationwide registry-based cohort study including all children under 15 years of age diagnosed with cancer in Denmark over a 23-year period (1996-2018). The Danish National Patient Registry was used to identify musculoskeletal diagnoses and associated dates recorded within 6 months preceding the diagnosis of cancer. We compared the characteristics of children with and without a prior musculoskeletal diagnoses using prevalence ratios and 95% CI and diagnostic interval as median with IQR. We compared survival using Kaplan-Meier and Cox proportional hazards regression analysis adjusting for age, sex, and presence of metastasis at diagnosis. RESULTS: Of 3895 children with all types of cancer, 264 (7%) had a total of 451 hospital visits with musculoskeletal diagnosis within 6 months preceding the diagnosis of cancer; however, survival was not affected. The overall median diagnostic interval from first musculoskeletal diagnosis (within 6 months before cancer diagnosis) to cancer diagnosis was 15 days (IQR, 7-47 days). A diagnosis of juvenile idiopathic arthritis, unspecified arthritis, and arthropathy each accounted for 5% of the contacts, primarily in children with acute lymphoblastic leukemia, bone sarcomas, or neuroblastomas. CONCLUSIONS: A preliminary musculoskeletal diagnosis occurred in 7% of children with cancer, but did not affect the overall survival.

Prolonged rectal shedding of SARS-CoV-2 in a 22-day-old-neonate: a case report.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the novel coronavirus disease 2019 (COVID-19), which is characterized by a diverse clinical picture. Children are often asymptomatic or experience mild symptoms and have a milder disease course compared to adults. Rectal shedding of SARS-CoV-2 has been observed in both adults and children, suggesting the fecal-oral route as a potential route of transmission. However, only a few studies have investigated this in neonates. We present a neonate with a mild disease course and prolonged rectal SARS-CoV-2 shedding. CASE PRESENTATION: A 22-day old neonate was admitted to the hospital with tachycardia and a family history of COVID-19. The boy later tested positive for COVID-19. His heart rate normalized overnight without intervention , but a grade 1/6 heart murmur on the left side of the sternum was found. After excluding signs of heart failure, the boy was discharged in a habitual state after three days of admission. During his admission, he was enrolled in a clinical study examining the rectal shedding of SARS-CoV-2. He was positive for SARS-CoV-2 in his pharyngeal swabs for 11 days after initial diagnosis and remained positive in his rectal swabs for 45 days. Thereby, the boy remained positive in his rectal swabs for 29 days after his first negative pharyngeal swab. CONCLUSIONS: The presented case shows that neonates with a mild disease course can shed SARS-CoV-2 in the intestines for 45 days. In the current case, it was not possible to determine if fecal-oral transfer to the family occurred, and more research is needed to establish the potential risk of the fecal-oral transmission route.

Description of the voided urinary microbiota in asymptomatic prepubertal children - A pilot study.

BACKGROUND: Recently, it has been established that the urine of a healthy adult bladder contains a microbiota and that urinary dysbiosis may be involved in the development of urinary tract diseases. The urinary microbiota and its relation to bladder health and disease in children is yet to be established. The objective of the present study was to investigate the voided urinary microbiota in asymptomatic prepubertal children. STUDY DESIGN: Thirty asymptomatic children (15 boys and 15 girls) participated in the study. Bacterial DNA in "clean-catch" midstream urine (CC MSU) samples was analysed using Illumina MiSeq sequencing of the V4 region of the bacterial 16 S rRNA gene. All children had normal bladder function as ensured by uroflowmetry, ultrasonic post-void residual, and frequency-volume charts. Bladder-related parameters and gender comparisons were analysed statistically by parametric and non-parametric tests. Alpha diversity, beta diversity, and a Venn diagram were used to analyse sequencing data. RESULTS: All CC MSU samples contained bacterial DNA. The voided urinary microbiota differed significantly between girls and boys in terms of operational taxonomic unit (OTU) richness, Shannon diversity index, and relative abundances of bacterial genera, but not for evenness. The urine of girls was dominated by Prevotella (18.2%), Porphyromonas (12.9%), Ezakiella (8.1%), Prevotella 6 (7.4%), and Dialister (7.0%). Porphyromonas (22.4%) was the most abundant genus in boys, followed by Ezakiella (12.0%), Campylobacter (11.6%), Prevotella (8.6%), and Dialister (3.7%). Girls had 10 unique core OTUs, whereas boys had no unique core OTUs. Porphyromonas appeared as a shared core OTU between genders. DISCUSSION: Contrary to previous findings, this study found significant differences in the voided urinary bacterial composition among asymptomatic prepubertal children. Moreover, the bacterial composition diverged from that found among healthy adults by other research groups. Among adults, the gender specific urinary microbiota has been hypothesised to be caused by anatomical differences in the reproductive organs and differences in sex hormone levels. This could also be evident for asymptomatic prepubertal children as sex hormone levels are different even at the prepubertal stage. The limitations of the study encompass small sample size and urine collection by CC MSU with risk of contamination from surrounding areas. CONCLUSIONS: This study documents that CC MSU samples of asymptomatic prepubertal children are not sterile. The composition of the voided urinary microbiota seems gender specific and unequal to that of healthy adults. The role of the urinary microbiota in paediatric urological disorders should be considered in future studies.