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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. 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.

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.

ObjectiveChildhood 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 designIn 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).ResultsOf 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.ConclusionMusculoskeletal misdiagnoses were rare in children with brain tumors and did not affect the diagnostic time interval or survival. The misdiagnoses consisted primarily of torticollis- or otherwise neck-related diagnoses.

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.

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.

Recent studies suggest that alterations in the female urinary microbiota is associated to development of bladder disease. However, the normal microbiota composition and variation in healthy women are poorly described. Moreover, the effects of hormonal changes on microbiota during menopause is not well understood. The aim of our study was to investigate the urinary microbiota in healthy pre- and postmenopausal women without urinary tract symptoms. Microbiota composition in catheterized urine samples was mapped using 16S rRNA gene sequencing. In total, 41 premenopausal and 42 postmenopausal women were initially included. Samples with first PCR amplification concentration below level of the negative control were excluded, resulting in 34 premenopausal and 20 postmenopausal women included in data analysis. Urine from postmenopausal women showed significantly higher alpha diversity compared to premenopausal women. Lactobacillus was the most abundant bacteria in both groups, however the relative abundance of Lactobacillus accounted for 77.8% in premenopausal versus 42.0% in postmenopausal women. In conclusion, urine from premenopausal mostly presented with Lactobacillus dominated urotypes, whereas urine from postmenopausal women presented a more diverse urinary microbiota with higher abundance of the genera Gardnerella and Prevotella. The clinical and pathophysiological implications of this difference remain to be elucidated.

Objectives: Investigate characteristics of term infants culture-evaluated for early-onset sepsis (EOS) in neonatal intensive care units (NICUs), frequencies of organisms causing EOS, and factors associated with EOS. Study design: Using a cohort design, we identified term infants evaluated for EOS with blood, cerebrospinal fluid, or urine cultures in 326 NICUs (2011–2016). Using multivariable logistic regression, we investigated the association between EOS and demographic characteristics. Results: Of 142,410 infants, 1197 (0.8%) had EOS, most commonly caused by group B Streptococcus (GBS; 40.6%). Lower EOS risk was associated with low Apgar score, Cesarean delivery, small for gestational age, prenatal antibiotic exposure, and positive or unknown maternal GBS screening result. Increased risk was associated with prolonged rupture of membranes, maternal age

Accumulating evidence has implicated an involvement of the gut-brain axis in autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD), however with highly diverse results. This systematic review aims to describe and evaluate studies investigating the gut microbiota composition in individuals with ASD or ADHD and to evaluate if variations in gut microbiota are associated with these disorders. Twenty-four articles were identified in a systematic literature search of PubMed and Embase up to July 22, 2019. They consisted of 20 studies investigating ASD and four studies investigating ADHD. For ASD, several studies agreed on an overall difference in β-diversity, although no consistent bacterial variation between all studies was reported. For ADHD, the results were more diverse, with no clear differences observed. Several common characteristics in gut microbiota function were identified for ASD compared to controls. In contrast, highly heterogeneous results were reported for ADHD, and thus the association between gut microbiota composition and ADHD remains unclear. For both disorders, methodological differences hampered the comparison of studies.

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.

OBJECTIVE: To identify the prevalence of musculoskeletal diagnoses recorded six months prior to 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 (DNPR) was used to identify musculoskeletal diagnoses and associated dates recorded within six months preceding the diagnosis of cancer. We compared characteristics of children with and without a prior musculoskeletal diagnoses using prevalence ratios and 95% confidence intervals (CI) and diagnostic interval as median with interquartile range (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 3,895 children with all types of cancer, 264 (7%) had a total of 451 hospital visits with musculoskeletal diagnosis within six 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). 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.CONCLUSION: A preliminary musculoskeletal diagnosis occurred in 7% of children with cancer but did not affect overall survival.

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 CONCLUSIONS: TENS as add-on to anticholinergic treatment seems effective in a number of children with treatment-refractory DUI.

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.

AIM: To investigate the efficacy and safety of home-treatment with oral piv-mecillinam or amoxicillin-clavulanate in children with acute pyelonephritis.METHODS: Children aged over 6 months diagnosed with culture confirmed pyelonephritis at Danish Paediatric Departments were home-treated with piv-mecillinam (tablets) or amoxicillin-clavulanate (liquid or tablets). Follow-up was performed by phone (second treatment day) and clinical review of the patients in the hospital (day three).RESULTS: Four hundred eighteen children were included. In total, 333/418 (80%) responded well to the initial oral antibiotic treatment. 85/418 (20%) were changed to another treatment of these 47/418 (11%) to a second-line oral antibiotic and 38/418 (9%) to intravenous antibiotics due to insufficient clinical improvement or bacterial resistance. Bacterial resistance was similar for piv-mecillinam and amoxicillin-clavulanate: 4/74 (5%) versus 33/333 (10%) (p = 0.22). Insufficient clinical improvement, despite no resistance, primarily occurred in children treated with piv-mecillinam: 16/74 (22%) versus 28/344 (8%) (p < 0.001), and predominantly occurred in piv-mecillinam treated children CONCLUSION: A home-treatment regime for pyelonephritis in children >6 months is safe; however, during treatment, clinical re-evaluation is required as in 20% of cases a change in treatment was necessary.

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.

INTRODUCTION: Childhood irritant contact dermatitis (ICD) is the most common cause for developing chronic hand eczema as an adult. The COVID-19 reopening in Denmark included regulations introducing frequent hand washing. The aim of the present study was to evaluate if frequent hand washing increases the incidence of ICD in children.METHODS: We conducted an observational study in Denmark during the reopening of schools and daycare facilities for children aged 0-12 years (April 22nd to May 1st 2020). A questionnaire was sent out to parents in four municipalities consisting of 20 questions about frequency of hand washing, use of hand sanitiser, symptoms of ICD, atopic dermatitis, allergy and predispositions.RESULTS: The study included 6,273 children. In children without any prior symptoms of dermatitis, 42.4% experienced ICD (dry, red and itchy skin) due to increased hand hygiene. Schoolchildren had a 1.5 times greater relative risk of developing ICD than preschool children. Frequency of hand washing was a strong risk factor, whereas this was not the case for alcohol-based hand sanitiser. Hand washing 7-10 times/day and >10 times/day increased the relative risk by 1.83 and 2.23 times, respectively.CONCLUSIONS: A higher frequency of hand washing during the COVID-19 reopening increased the incidence of ICD in children. Hand hygiene is essential in our fight against novel coronavirus, but prophylactic initiatives are important to reduce the possible long-term consequences of ICD in children.FUNDING: none TRIAL REGISTRATION: Clinicaltrials.gov (NCT04375410).

It remains unknown how Coronavirus disease-2019 (COVID-19) prevention measures implemented on March 12, 2020, have affected the rate of pediatric infection-related hospitalizations in Denmark. Therefore, we investigated the rate of pediatric infection–related hospitalizations during the COVID-19 pandemic. We used a retrospective cohort design and included all Danish children < 18 years. Infection-related hospitalizations were assessed during study periods in 2020 vs. 2018/2019, and we computed incidence rate ratios (IRRs) with 95% confidence intervals (CIs) using Poisson regression. In the 2020 study period, 3093 children were hospitalized with an infection, while the corresponding figures for 2018 and 2019 study periods were 4824 and 3830, respectively. When comparing the 2020 to the 2018/2019 study period prior to nationwide lockdown, we observed a decline in infection-related hospitalizations (12.68 (95% CI, 12.22–13.16) vs. 15.49 (95% CI, 15.12–15.86) per 1000 person-years). We further observed decreased IRRs, especially during the lockdown period (week 11: 0.64 (95% CI, 0.55–0.75); week 12: 0.26 (95% CI, 0.21–0.33); week 13: 0.13 (95% CI, 0.10–0.19)). Conclusion: The rate of pediatric infection-related hospitalizations in Denmark declined during the COVID-19 pandemic in 2020 compared to that in 2018/2019, with a 36% decline during initiation of the nationwide lockdown period.What is Known:• Due to the COVID-19 pandemic, several countries have implemented mitigation strategies such as lockdown of non-critical business functions. Most of these strategies have previously been proven effective on interruption of infection transmission.• It remains unclear how the mitigation strategies have affected the rate of pediatric infection–related hospitalizations.What is New:• Insight on how COVID-19 prevention measures have affected the frequency of infection-related hospitalization.• Valuable knowledge on how to act in potential future pandemics. Supplementary Information The online version contains supplementary material available at 10.1007/s00431-021-03934-2.

ObjectivesIn utero exposure to antiepileptic drugs has previously been associated with adverse outcome among offspring, but evidence on longer term milestone development remains limited. We investigated the association between in utero exposure to antiepileptic drugs and learning disabilities in the first year of compulsory education among offspring and assessed which antiepileptic drugs carried the highest risk.MethodsThis population-based case–cohort study used Danish nationwide register data from 2005 to 2008. Cases were offspring exposed to antiepileptic drugs in utero, and controls were unexposed offspring of mothers previously redeeming antiepileptic drug prescriptions. Offspring were followed from birth until the first year of compulsory education from 2011 to 2015. Learning disabilities were defined as mental retardation, specific developmental disorders, autism spectrum disorders, emotional/behavioural disorders or having special educational needs. Logistic regression was used to compute ORs with 95% CIs adjusted for potential confounding.ResultsOf 117 475 incident singleton births, 636 cases and 434 controls were included (median age: 6.1 years, males: 55.7%). Learning disabilities were identified among 7.1% cases compared with 3.7% for controls. During any trimester, the adjusted OR of the association between in utero exposure to antiepileptic drugs and learning disabilities was 2.20 (95% CI 1.16 to 4.17). Among cases not exposed to polytherapy (n=556), in utero exposure to lamotrigine compared with another antiepileptic drug was associated with the lowest adjusted risk (OR 0.42, 95% CI 0.19 to 0.92), and valproate carried a higher risk (OR 4.67, 95% CI 1.73 to 12.59).ConclusionIn utero exposure to antiepileptic drugs was significantly associated with learning disabilities among offspring. Lamotrigine should preferentially be considered over, for example, valproate if clinically feasible.

Congenital nephrogenic diabetes insipidus (CNDI) is characterized by the reduced ability of renal collecting duct cells to reabsorb water in response to the antidiuretic effect of vasopressin. Chronic polyuria and polydipsia are the hallmarks of the disease. Approximately 90% of all patients with CNDI have X-linked inherited disease caused by variants in the arginine vasopressin receptor 2 (AVPR2) gene. We present genetic findings in 34 individuals from 19 kindreds including one or more family members with CNDI. Coding regions of AVPR2 were sequenced bi-directionally. We identified eight novel disease-causing variants in AVPR2, p.Arg68Alafs*124, p.Ser171Arg, p.Gln174Pro, p.Trp200Arg, p.Gly201Cys, p.Gly220Arg, p.Val226Glu, and p.Gln291Pro in nine kindreds. In all three families with more than one affected individual, the novel variants segregated with the disease. We also identified eight recurrent disease-causing variants, p.Val88Met, p.Leu111Valfs*80, p.Arg113Trp, p.Tyr124*, p.Ser167Leu, p.Thr207Asn, p.Arg247Alafs*12, and p.Arg337* in ten kindreds. Our findings contribute to the growing list of AVPR2 variants causing X-linked CNDI.CONCLUSION: Being a rapid diagnostic tool for CNDI, direct sequencing of AVPR2 should be encouraged in newborns with familial predisposition to CNDI. What is Known: • Disease-causing variants in AVPR2 cause X-linked congenital nephrogenic diabetes insipidus (CNDI). • DNA sequencing of AVPR2 is rapid, facilitates differential diagnosis, early intervention, and genetic diagnosis thus reducing morbidity in CNDI. What is New: • We identified eight novel disease-causing variants in AVPR2: p.Arg68Alafs*124, p.Ser171Arg, p.Gln174Pro, p.Trp200Arg, p.Gly201Cys, p.Gly220Arg, p.Val226Glu, and p.Gln291Pro, thereby adding to the growing list of AVPR2 disease-causing variants and emphasizing the importance of genetic testing in CNDI.

BackgroundNew sensitive techniques have revealed a large population of bacteria in the human urinary tract, challenging the perception of the urine of healthy humans being sterile. While the role of this urinary microbiota is unknown, dysbiosis has been linked to disorders like urgency urinary incontinence and interstitial cystitis. When comparing studies it is crucial to account for possible confounders introduced due to methodological differences. Here we investigated whether storage condition or time of collection, had any impact on the urinary microbial composition.ResultsFor comparison of different storage conditions, urine was collected from five healthy adult female donors, and analyzed by 16S rRNA gene sequencing. Using the same methods, the daily or day-to-day variation in urinary microbiota was investigated in nineteen healthy donors, including four women, five men, five girls, and five boys. With the exception of two male adult donors, none of the tested conditions gave rise to significant differences in alpha and beta diversities between individuals. Conclusion: The composition of the urinary microbiota was found to be highly resilient to changes introduced by storage temperature and duration. In addition, we did not observe any intrapersonal daily or day-to-day variations in microbiota composition in women, girls or boys.Together our study supports flexibility in study design, when conducting urinary microbiota studies.Author summaryThe discovery of bacteria native to the urinary tract in healthy people, a location previously believed to be sterile, has prompted research into the clinical potential of these bacteria. However, methodological weaknesses can significantly influence such studies, and thus development of robust techniques for investigating these bacteria are needed. In the present study, we investigated whether differences in storage following collection, could affect the bacterial composition of urine samples. Next, we investigated if this composition exhibited daily or day-to-day variations.Firstly, we found, that the bacterial composition of urine could be maintained by storage at −80 °C, −20 °C, or refrigerated at 4 °C. Secondly, the bacterial composition of urine remained stable over time. Overall, the results of this study provide information important to study design in future investigations into the clinical implications of urinary bacteria.

This case report presents a three-month-old girl, previously healthy, who was admitted to the hospital due to a cyanotic episode during breastfeeding. The episode was initially interpreted as aspiration. She had recurrent generalised seizures, and blood tests revealed hypomagnesaemia and hypocalcaemia. The electrolyte abnormalities were corrected by intravenous magnesium with subsequent normalisation of the calcium level. Genetic testing discovered a deletion in the TRPM6, which is associated with familial hypomagne-s-aemia with secondary hypocalcaemia. It is important to identify electrolyte disturbances in infants with afebrile seizures.

BACKGROUND: Childhood steroid-sensitive nephrotic syndrome (SSNS) has previously been assumed to be a disease of childhood. This has been challenged by few studies reporting that some patients with childhood SSNS may continue to relapse into adulthood. The aim of this study was to investigate the long-term outcome of childhood SSNS presenting data from an unselected well-defined cohort of Danish patients.METHODS: We conducted a retrospective study of the clinical outcome from a population of patients consecutively admitted to the pediatric departments in the central and northern region of Denmark from 1998 to 2015. Patients were followed until August 2017. Data were collected from the patient's medical records.RESULTS: Long-term outcome was studied in 39 adult patients with childhood onset SSNS. A total of 31% (12/39) had active disease in adulthood. Univariate analysis showed that more severe forms of SSNS (e.g., steroid dependent/frequent relapsing (SD/FR) nephrotic syndrome) in childhood were associated with active disease in adulthood. Comparing adult patients with SD/FR showed a significantly higher number of relapses/patient/year from late childhood and adolescence in the group with active disease vs. non-active disease (1.06 (95%CI: 0.32-1.81) vs. 0.19 (95%CI: 0.06-0.31, p = 0.005).CONCLUSION: In general, one third of all patients with SSNS during childhood continue to have active disease during early adulthood, in particular patients with SD/FR continue to suffer from active disease. The present data illustrates that SSNS is not just a disease of childhood but persists in adulthood in a significant number of patients.

Summary Introduction Fecal and urinary incontinence are common disorders in children. Obesity and its associated comorbidities have become increasingly common, and a relation between obesity, nocturia, incontinence, and nocturnal enuresis has been suggested. Objective This large scale population study aims to determine the prevalence of fecal incontinence (FI), daytime urinary incontinence (DUI), nocturnal enuresis (NE), and nocturia in children at school entry and in adolescence and to clarify whether obesity is associated to any of the aforementioned symptoms. Study design First-grade children and their parents and adolescents in the seventh to ninth grades were interviewed in relation to school nurse visits. The interview included questions on whether incontinence or nocturia were experienced at least once per month. The participants' age was recorded, and weight and height were measured. Body mass index (BMI) was calculated and age standardized by the use of BMI-standard deviation score (SDS), with reference to World Health Organization normative BMI data. Obesity was defined as BMI-SDS >2. Associations between obesity and incontinence and nocturia were quantified by odds ratio (OR). Results Completed interview questionnaires and measurements were obtained from 4002 children (95.1%) in the child population and 2801 adolescents (84.4%) in the adolescent population. The mean age of children was 6.45 ± 0.39 years, and 4.4% were obese. Overall 11.2% reported FI, 21.8% DUI, 16.8% NE, and 31.4% experienced nocturia. Obesity was associated with FI in first-grade boys (OR 1.86 compared with normal weight). Mean age of adolescents was 13.9 ± 0.85 years, and 7.6% of adolescent boys and 5.5% of the girls were obese. Fecal incontinence was reported by 2.1% of the adolescents, 4.5% had DUI, 1.0% stated to have NE, and 32.3% reported nocturia. Obesity was significantly associated with nocturia in adolescents (OR 1.74–2.01). Discussion The prevalence of nocturia seems constant throughout childhood and adolescent life; this has not previously been documented. Incontinence is very common at school entry, with DUI reported more frequently than enuresis by both children and adolescents. Obesity is associated with nocturia in adolescents and FI in first-grade boys, but no significant association between obesity and NE or DUI is found. Strength of this study is the very high participation rates, but the study does not reveal information on previous treatment, subtype, or severity of symptoms. Conclusions Incontinence is very common in children. One-third of both children and adolescents experience nocturia. Obesity is associated with FI in first-grade boys and nocturia in adolescents.

Due to ease of acquisition, fecal samples are often used in studies investigating gut microbiota. Improper handling of these samples can lead to bacterial growth and alter bacterial composition. While freezing samples at −80 °C is considered gold standard, this is not suitable for studies utilizing self-sampling by lay participants or field studies. Thus to effectively prevent bacterial growth, techniques that allow efficient fecal storage outside laboratory facilities are needed. Fecal samples were collected from three donors. From each donor feces, 45 samples were collected and stored either freshly frozen at −80 or −20 °C, or in three separate storage buffers at room temperature or 4 °C for 24 or 72 hours. Bacterial composition was analyzed using Illumina amplicon sequencing of the V4 region of the 16 S rRNA gene. While storage conditions did affect bacterial composition and diversity compared to storage at −80 °C, the variation between donors superseded the variations introduced by storage. Samples stored at −20 °C most closely resembled those stored at −80 °C. When investigating variations in bacterial composition between separate study populations, fecal samples can efficiently be stored in −20 °C freezers or in one of the presented storage buffers, without severe alterations in bacterial composition.

Caspar Bundgaard-Nielsen1,2, Anne Sofie Hansen3, Marlene Briciet Lauritsen3, Mette Nyegaard4, Søren Hagstrøm1,2,5, Suzette Sørensen1,2

Background. Oedema formation in nephrotic syndrome (NS) may be associated with volume overload or volume contraction. The present study investigates if plasma aldosterone was related to a clinical course symptomatic of either volume expansion or hypovolaemia. Methods. Twenty patients with NS were included. Blood and urine samples were collected before treatment of NS and at stable remission. Aldosterone and other vasoactive hormones were measured in plasma and the patients were classified based on the aldosterone concentrations. Results. Five patients were classified with stimulated aldosterone, mean 611 pg/mL [95% confidence interval (CI): 365–993], 12 with suppressed aldosterone, mean 13 pg/mL (95% CI: 6–26), and 3 with unchanged aldosterone, mean 117 pg/mL (95% CI: 101–135). Patients with high aldosterone were characterized by lower estimated glomerular filtration rate (eGFR) (87 ± 30 versus 142 ± 30, P < 0.01), and increased albuminuria (14 ± 11 versus 6 ± 4 g/L, P = 0.03) compared with the remaining patients. eGFR was normalized rapidly by volume expansion in four of these five patients. Conclusions. Elevated plasma aldosterone during NS may be associated with a risk of temporary reduced eGFR. The normalization of eGFR by volume expansion supports the hypothesis of functional hypovolaemia in some patients. Our data suggest that acute measurement of aldosterone may have implications for the management of oedema.