Resilience strengthening in youth with a chronic medical condition: a randomized controlled feasibility trial of a combined app and coaching program.

Youth with a chronic medical condition (CMC) are often affected by comorbid mental disorders. Resilience-strengthening interventions can protect youth's mental health, yet evidence-based programs remain scarce. To address this lack, this study aimed to evaluate the feasibility of a dual approach combining app-based resilience training and cognitive behavioral group coaching. Fifty-one youths with CMC treated at a German university children's hospital aged 12-16 years were recruited. They were randomly assigned to a combined app game and coaching intervention or sole app gameplay. At pre-, post-intervention, and at a 2-month follow-up resilience, automatic negative thoughts and an app and coaching evaluation were assessed. Feasibility was defined as a recruitment rate of 70%, an 85% adherence rate for the REThink game, and 70% participation in both coaching sessions. Feasibility criteria were reached for coaching participation but not for recruitment or app adherence. While both the REThink game app and coaching intervention had high acceptance rates among youth with CMC, participants receiving additional coaching sessions showed higher satisfaction and adherence rates. Participants preferred remote to in-person meetings. The findings support a combination of a gamification app approach with online group coaching. Group coaching can improve adherence while online options increase accessibility. Future research should focus on testing in diverse participant samples, language, and age-adapted updates of the REThink game app. These findings provide guidance for increasing adherence in future intervention studies in youth with CMC cohorts.

Evaluation of lipoprotein-associated phospholipase A2 as a marker for renal microvasculopathy in adolescents with Type 1 diabetes.

AIM: To assess the relevance of lipoprotein-associated phospholipase A2 activity as a diagnostic and prognostic marker for renal microvascular diseases. METHODS: We analysed lipoprotein-associated phospholipase A2 activity and lysophosphatidylcholine levels (as a surrogate marker of oxidative stress) in 165 adolescents (aged 17.0 ± 2.3 years) with a history of Type 1 diabetes greater than 10 years. Clinical data were obtained from the German/Austrian nationwide Diabetes-Patients Follow-up (DPV) registry at blood collection and on average 2.4 ± 1.3 years later at follow-up. Relationships between lipoprotein-associated phospholipase A2 activity and clinical, demographic and laboratory variables, lysophosphatidylcholine levels and presence of albuminuria were evaluated by multivariable linear and logistic regression. RESULTS: Lipoprotein-associated phospholipase A2 activity was higher in male than female adolescents (P = 0.002). Albuminuria was present in 14% (22/158) of participants at baseline, and 5% (4/86) of participants without albuminuria at baseline developed albuminuria until follow-up. Lipoprotein-associated phospholipase A2 activity was associated neither with present nor with incident albuminuria. Lysophosphatidylcholine did not correlate with lipoprotein-associated phospholipase A2 activity. Cross-sectional bivariate correlation as well as multivariable linear regression analysis revealed a negative correlation of lipoprotein-associated phospholipase A2 activity with HbA1c and HDL-cholesterol. CONCLUSIONS: Lipoprotein-associated phospholipase activity was not associated with surrogate markers for oxidative stress and early diabetic nephropathy. The association of decreased lipoprotein-associated phospholipase A2 activity with poor glucose control might limit its function as a predictor of micro- and macrovascular diseases in Type 1 diabetes.

Multiple cytokines for the detection of Mycobacterium tuberculosis infection in children with tuberculosis.

SETTING: Interferon-gamma (IFN-γ) release assays (IGRAs) play an important role in the diagnosis of Mycobacterium tuberculosis infection. However, in children with tuberculosis (TB), some studies have shown increased frequencies of false-negative or indeterminate IGRA results. OBJECTIVE: To analyse the spectrum of different cytokines to improve the diagnostic accuracy of IGRAs in latent tuberculous infection (LTBI) and active TB. DESIGN: We performed multiplex cytokine expression analysis of QuantiFERON® Gold In-Tube supernatants in children with active TB (n = 21) and disease-free contacts with (n = 15) and without LTBI (n = 12), to determine the sensitivity and specificity of the modified tests. RESULTS: Of 21 initial cytokines analysed, IFN-γ and six other candidates (interleukin [IL] 2, inducible protein 10 [IP-10], IL-13, IL-1α, tumour necrosis factor alpha [TNF-α] and granulocyte-macrophage colony-stimulating factor [GM-CSF]) were significantly more elevated in children with TB and those with LTBI than in the non-infected controls. Sensitivity and specificity were similar for IFN-γ and IL-2, but lower for the remaining candidates. Notably, a subset of candidates, including IP-10, showed M. tuberculosis antigen-induced specific expression in non-infected children. None of the candidates showed differences in expression between children with TB and those with LTBI. CONCLUSIONS: Our results did not suggest that alternative IGRA cytokines can distinguish between children with active TB and those with LTBI. IFN-γ and IL-2 showed comparable capacity in diagnosing M. tuberculosis infection in our study groups.

Need for Better Diabetes Treatment: The Therapeutic Potential of NMDA Receptor Antagonists.

Diabetes mellitus is the most common metabolic disorder in children and adolescents. Optimal control of blood glucose concentration is essential to prevent acute and diabetic long-term complications. The options to treat diabetes have clearly improved over the last decades, however, to date neither type 1 diabetes nor type 2 diabetes mellitus can be cured. Therefore, diabetes research aims at developing ß-cell protective agents that prevent or even reverse diabetes onset. N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels that are widely expressed in the central nervous system (CNS) where they hold central roles in CNS function. NMDAR dysfunction is associated with several neurological and psychiatric disorders and therefore NMDAR modulators have several potential therapeutic indications. Only little is known about the role of pancreatic NMDA receptors. Our data provide evidence that inhibition of pancreatic NMDARs, either genetically or pharmacologically with the over-the-counter drug dextromethorphan, increases glucose-stimulated insulin secretion from mouse and human pancreatic islets, improves glucose tolerance in mice and individuals with diabetes and promotes islet cell survival under diabetogenic conditions. Thus, our data indicate for the first time that NMDAR antagonists could serve as adjunct treatment for diabetes mellitus. The development of a safe, blood glucose lowering and particularly ß-cell protective medication would significantly enhance current diabetes treatment.

Intrahepatic cholestasis of pregnancy (ICP): case report and review of the literature.

Intrahepatic cholestasis of pregnancy (ICP) represents the most common pregnancy-related liver disease in women. Women frequently present in the third trimester with pruritus and elevated serum bile acid and/or alanine transaminase levels. Clinical symptoms quickly resolve after delivery; however, recurrence in subsequent pregnancies has to be expected. Intrahepatic cholestasis of pregnancy is associated with increased perinatal complications, such as premature delivery, meconium staining of the amniotic fluid, respiratory distress, low Apgar scores, and even stillbirth. The risk for the fetus is significantly increased with maternal serum bile acid levels above 40 µmol/L, which characterize severe ICP. An important factor for ICP development is a rise of gestational hormones leading to cholestasis in genetically predisposed women. Variants in the bile salt export pump (BSEP) and the multidrug resistance protein 3 (MDR3) are most often identified in ICP. Here, we give an overview of the current literature on ICP and present the case of a woman with recurrent severe ICP. A common BSEP polymorphism as well as a rare MDR3 mutation may underlie the development of ICP in our patient. She had a premature delivery with meconium staining of the amniotic fluid. The neonate showed signs of respiratory distress with a low Apgar score. This case emphasizes that women with severe ICP have an increased risk for perinatal complications. Furthermore, severe ICP was associated with a MDR3 mutation, which has already been described in adult patients with liver cirrhosis. Thus, ICP may unmask an underlying MDR3 defect, which may predispose to development of hepatobiliary diseases such as gallstone disease, liver fibrosis/cirrhosis, as well as hepatobiliary malignancies. Therefore, genetic testing should be considered in women with severe as well as early onset ICP. Furthermore, regular follow-up should be discussed for women with genetic variants.

Hyperargininemia due to arginase I deficiency: the original patients and their natural history, and a review of the literature.

Hyperargininemia is caused by deficiency of arginase 1, which catalyzes the hydrolysis of L-arginine to urea as the final enzyme in the urea cycle. In contrast to other urea cycle defects, arginase 1 deficiency usually does not cause catastrophic neonatal hyperammonemia but rather presents with progressive neurological symptoms including seizures and spastic paraplegia in the first years of life and hepatic pathology, such as neonatal cholestasis, acute liver failure, or liver fibrosis. Some patients have developed hepatocellular carcinoma. A usually mild or moderate hyperammonemia may occur at any age. The pathogenesis of arginase I deficiency is yet not fully understood. However, the accumulation of L-arginine and the resulting abnormalities in the metabolism of guanidine compounds and nitric oxide have been proposed to play a major pathophysiological role. This article provides an update on the first patients ever described, gives an overview of the distinct clinical characteristics, biochemical as well as genetical background and discusses treatment options.

Evaluation of Acoustic Radiation Force Impulse Imaging (ARFI) for the Determination of Liver Stiffness Using Transient Elastography as a Reference in Children.

PURPOSE: Transient elastography (Fibroscan(©); (FS)) and acoustic radiation force impulse imaging (ARFI) represent noninvasive, user-friendly and quick methods providing an objective and reproducible measure of liver stiffness. The aim of the study was to evaluate cut-off values and performance of ARFI measurements in children using transient elastography as a reference. METHODS/PATIENTS: A total of 198 children were enrolled in this study. All patients underwent liver stiffness measurements with FS (FS-LS) as well as ARFI (with shear wave velocity quantification; ARFI-SWV) and the performance of ARFI in comparison to FS was studied. RESULTS: Significantly higher rates of successful measurements were found for ARFI compared to FS (198/198 (100%) vs. 160/198 (80.8%); p<0.001). ARFI-SWV correlated significantly with FS-LS (r=0.751, p=0.001). ARFI-SWV increased significantly with the stage of fibrosis (1.19+0.15 m/s for patients with FS-LS<7.6 kPa); 1.34+0.22 m/s for patients with 7.613.0 kPa). ARFI-SWV cut-off values were identified for no significant fibrosis (1.31 m/s; sensitivity 61.8% and specificity 79.5%) and for liver cirrhosis (1.63 m/s; sensitivity 70.0% and specificity 97.4%). The median values of liver stiffness measured by FS were age-dependent in 90 children without liver diseases with 4.8, 5.6, and 5.7 kPa in children 0-5, 6-11, and 12-18 years, respectively.

Fatal non-accidental alpha-lipoic acid intoxication in an adolescent girl.

The aim of our report is to increase awareness that the antioxidant alpha-lipoic acid, which is marketed primarily as weight loss and energy supplement, has potentially lethal effects. A 14-year-old girl ingested in suicidal intention a large amount of alpha-lipoic acid, which led to multiorgan failure and subsequent death within 24 h. Multiorgan failure consisted of decreased myocardial contractility, seizures, anuria, thrombocytopenia, and coagulopathy. Therapy consisted of ventilation, anticonvulsive treatment and circulatory support with high-dose catecholamines. According to alpha-lipoic acid serum levels following ingestion the girl must have ingested a minimum of 10 alpha-lipoic acid tablets of 600 mg each. This is the first report on a fatal case of alpha-lipoic acid ingestion, which is intended to inform physicians, pharmacists and patients about critical side effects of this allegedly innocuous drug.

Nasogastric vs. intravenous rehydration in children with gastroenteritis and refusal to drink: a randomized controlled trial.

BACKGROUND: Nasogastric rehydration therapy (NGRT) is the recommended therapy in moderately dehydrated children with gastroenteritis and refusal to drink, since it is supposed to be as effective if not better than intravenous rehydration therapy (IVRT). However, in clinical practice IVRT is often favored. We conducted a clinical trial to determine whether IVRT is not inferior to NGRT. PATIENTS AND METHODS: Children 3 months to 6 years of age with moderate dehydration and refusal to drink secondary to gastroenteritis were recruited. After clinical assessment of the degree of dehydration, patients were assigned randomly to receive either IVRT or NGRT over 6 h on the hospital ward. RESULTS: Recruitment did not yield the estimated number of patients. Mainly, non-enrollment was due to failure to obtain parental consent because IVRT was expected. 97 patients were enrolled in the study, 46 were randomized to NGRT and 51 to IVRT. There was no difference between IVRT and NGRT groups concerning length of hospital stay (2.2±1.1 days vs. 2.4±1.1 days), success of rehydration (78 vs. 76%) and adverse events. DISCUSSION: Since we had to terminate the study ahead of schedule due to a low recruiting rate, our results are not reliable. However, data from the literature shows that the widespread described superiority of NGRT over IVRT is seriously influenced by studies from developing countries questioning the applicability of the results to a setting available in high-income countries nowadays. CONCLUSION: Our study demonstrates the difficulties performing such a study in a high-income country to come to an objective and clearly evident final conclusion.

Neuromyelitis optica and pregnancy during therapeutic B cell depletion: infant exposure to anti-AQP4 antibody and prevention of rebound relapses with low-dose rituximab postpartum.

Neuromyelitis optica (NMO) predominantly affects women, some in childbearing age, and requires early therapeutic intervention to prevent disabling relapses. We report an anti-AQP4 antibody-seropositive patient who became pregnant seven months after low-dose (100 mg) rituximab application. Pregnancy showed no complications, and low-dose rituximab restarted two days after delivery resulted in neurological stability for 24 months. Remarkably, her otherwise healthy newborn presented with anti-AQP4 antibody and reduced B lymphocyte counts in umbilical cord blood, which normalized three months later. Confirming and extending previous reports, our case suggests that low-dose rituximab might be compatible with pregnancy and prevent rebound NMO disease activity postpartum.

Pseudotumor cerebri in childhood and adolescence -- results of a Germany-wide ESPED-survey.

BACKGROUND: No valid epidemiological data on Pseudotumor cerebri (PTC) in childhood and adolescence are available. This national survey aims to raise awareness of the PTC in paediatrics and contribute to a better understanding of age-related characteristics. METHODS: Over 1 year (January-December 2008) new cases of PTC in childhood and adolescence from all paediatric hospitals in Germany were collected by the German Paediatric Surveillance Unit for rare diseases (ESPED). RESULTS: With a total of 61 cases, an annual incidence of 0.5 per 100 000 children <18 years was found. Children of all age groups were affected. A female preponderance and obesity was only found in adolescents. Clinical presentation was variable. Headaches represent the most common symptom affecting prepubertal children less frequently. A wide range of vision problems could be documented (papilledema, visual loss, double vision, visual field defects, disturbed colour and stereo vision). In 10 patients no papilledema was found. Comorbidities were reported in 23% of patients. 14 children gained remission after lumbar puncture without medication. Acetazolamide was the drug of choice, with relatively low dosages used. Escalation strategies were variable. 2 patients were treated invasively (sinus venous stent, LP shunt). CONCLUSION: PTC in childhood and adolescence appears to be as frequent as in the general population. Unspecific clinical characteristics and the broad spectrum of ophthalmologic findings emphasize the importance of a skilful neuroophthalmological investigation. Inconsistent therapeutic approaches are most likely due to a lack of diagnostic and therapeutic standards. Present diagnostic criteria and guidelines for the management of paediatric PTC do not sufficiently consider paediatric aspects.

Successful management of neonatal hemochromatosis by exchange transfusion and immunoglobulin: a case report.

Neonatal hemochromatosis (NH) is a rare and severe liver disease of mainly intra-uterine onset, characterized by neonatal liver failure, hepatic and extrahepatic iron accumulation. This leads to an altered iron metabolism with resulting siderosis. The disease represents the most common cause of liver failure in neonates and is also the most common indication for neonatal liver transplantation. We present a case of a newborn diagnosed with NH and life threatening liver failure. Initial treatment consisted of chelation therapy and antioxidants, but lack of laboratory and clinical improvement led to an exchange transfusion followed by the singular substitution of intravenous immunoglobulin (IVIG). Both, exchange transfusion and IVIG were tolerated well and led to an improvement of the general condition of the patient and recovery of liver synthetic function. The subsequent favorable course of the disease is described in this case report.

Association of exercise-induced hyperinsulinaemic hypoglycaemia with MCT1-expressing insulinoma.

AIMS/HYPOTHESIS: Exercise-induced hyperinsulinism (EIHI) is a hypoglycaemic disorder characterised by inappropriate insulin secretion following anaerobic exercise or pyruvate load. Activating promoter mutations in the MCT1 gene (also known as SCLA16A1), coding for monocarboxylate transporter 1 (MCT1), were shown to associate with EIHI. Recently, transgenic Mct1 expression in pancreatic beta cells was shown to introduce EIHI symptoms in mice. To date, MCT1 has not been demonstrated in insulin-producing cells from an EIHI patient. METHODS: In vivo insulin secretion was studied during an exercise test before and after the resection of an insulinoma. The presence of MCT1 was analysed using immunohistochemistry followed by laser scanning microscopy, western blot analysis and real-time RT-PCR of MCT1. The presence of MCT1 protein was analysed in four additional insulinoma patients. RESULTS: Clinical testing revealed massive insulin secretion induced by anaerobic exercise preoperatively, but not postoperatively. MCT1 protein was not detected in the patient's normal islets. In contrast, immunoreactivity was clearly observed in the insulinoma tissue. Western blot analysis and real-time RT-PCR showed a four- to fivefold increase in MCT1 in the insulinoma tissue of the EIHI patient compared with human pancreatic islets. MCT1 protein was detected in three of four additional insulinomas. CONCLUSIONS/INTERPRETATION: We show for the first time that an MCT1-expressing insulinoma was associated with EIHI and that MCT1 might be present in most insulinomas. Our data suggest that MCT1 expression in human insulin-producing cells can lead to EIHI and warrant further studies on the role of MCT1 in human insulinoma patients.

Sedation of children during measurement of CSF opening pressure: lack of standardisation in German children with pseudotumor cerebri.

BACKGROUND: Diagnosis of pseudotumor cerebri (PTC) requires proper documentation of raised CSF opening-pressure. In childhood results may not be reliable due to insufficient sedation/analgesia or drug effects. We aimed to evaluate the current practice regarding pain and stress management in children undergoing lumbar puncture (LP) for pressure measurement. METHODS: A one-year survey was conducted involving 368 German paediatric departments. All children with newly diagnosed PTC should be reported. Details analyzed here included: age, sex, CSF opening pressure and type of procedural sedation and analgesia (PSA) during LP. RESULTS: 61 patients were analyzed, aged 6 months to 17 years. 29 patients (47%) did not receive any kind of PSA. In children receiving PSA the following regimens were used: Ketamine; Midazolam; Ketamine + Midazolam; Midazolam + Piritramide; Propofol; Profofol + Midazolam; general anaesthesia. CONCLUSION: Pain and stress management in children undergoing LP for CSF opening pressure measurement is often insufficient. Pain, stress and the variability of PSA regimen may be confounders of pressure measurement. In order to prevent false diagnoses of PTC and to obtain comparable results at different centers, a general consensus on PSA in children undergoing LP for CSF opening pressure measurements is required.

Bloody nipple discharge (BND) in an 8 months old girl and a 9 months old male--rational diagnostic approach.

Bloody nipple discharge in adults is, in men as well as in women, often a symptom of an underlying malignant disease. In respect of this, multiple invasive and mutilating diagnostic procedures have been performed in infants and older children. Apart from individual cases in older and pubertal children, in childhood benign conditions are most common and can be diagnosed by non-invasive diagnostic procedures. Here we discuss a rational diagnostic approach on the basis of 2 patients with bloody nipple discharge at the age of 8 and 9 months which resolved spontaneously without treatment after 3 and 6 months, respectively.