Adrenal function in adult long-term survivors of nephroblastoma and neuroblastoma

AbstractBackgroundAdrenal insufficiency, or relative insufficiency, might partly explain increased mortality rates in nephroblastoma and neuroblastoma survivors after unilateral adrenalectomy.ObjectiveTo assess adrenal function and its metabolic effects in survivors after adrenalectomy.MethodsIn this cross-sectional study, 67 adult long-term survivors of nephroblastoma, 36 survivors of neuroblastoma and 49 control subjects participated. Adrenal function was assessed by a 1μg short Synacthen-test. Levels of cortisol, adrenocorticotrophic hormone (ACTH), low (LDL-C) and high-density lipoprotein-cholesterol (HDL-C), triglycerides, apolipoprotein-B, glucose and insulin were assessed in blood samples taken at baseline. In addition, cortisol levels were assessed after 30 (t=30) and 60min. Homoeostatic Model Assessment (HOMA) was calculated.ResultsAdrenal insufficiency was not present in survivors. Interestingly, baseline serum cortisol levels were higher in survivors after unilateral adrenalectomy (mean 503nmol/l) (N=46) than in survivors with both adrenals intact (mean 393nmol/l, P=0.002) (N=52), and than in controls (mean 399nmol/l, P=0.013) (N=49). After correcting for age, sex and use of oral oestrogens, unilateral adrenalectomy was independently associated with elevated baseline cortisol and ACTH levels. Baseline cortisol levels were positively associated with triglycerides (P<0.001), LDL-C (P=0.004), apolipoprotein-B (P<0.001) and HOMA (P=0.008).ConclusionsNo adrenal insufficiency was observed in survivors of nephroblastoma and neuroblastoma. Survivors treated with unilateral adrenalectomy had relatively high basal cortisol and ACTH levels, indicating a higher central setpoint of the hypothalamic-pituitary-adrenal axis. This higher setpoint was associated with lipid concentrations and insulin resistance and can therefore influence the cardiovascular risk profile in long-term survivors of nephroblastoma and neuroblastoma

Dextroamphetamine Treatment in Children With Hypothalamic Obesity

INTRODUCTION: Hypothalamic obesity (HO) in children has severe health consequences. Lifestyle interventions are mostly insufficient and currently no drug treatment is approved for children with HO. Amphetamines are known for their stimulant side-effect on resting energy expenditure (REE) and suppressing of appetite. Earlier case series have shown positive effects of amphetamines on weight in children with acquired HO. We present our experiences with dextroamphetamine treatment in the, up to now, largest cohort of children with HO. METHODS: A retrospective cohort evaluation was performed of children with HO treated with dextroamphetamine at two academic endocrine pediatric clinics. Off-label use of dextroamphetamine was initiated in patients with progressive, therapy-resistant acquired or congenital HO. Anthropometrics, REE, self-reported (hyperphagic) behavior and energy level, and side effects were assessed at start and during treatment. RESULTS: Nineteen patients with a mean age of 12.3 ± 4.0 years had been treated with dextroamphetamine. In two patients, ΔBMI SDS could not be evaluated due to short treatment duration or the simultaneous start of extensive lifestyle treatment. Mean treatment duration of the 17 evaluated patients was 23.7 ± 12.7 months. Fourteen patients (n = 10 with acquired HO, n = 4 with congenital HO) responded by BMI decline or BMI stabilization (mean ΔBMI SDS of -0.6 ± 0.8, after a mean period of 22.4 ± 10.5 months). In three patients, BMI SDS increased (mean ΔBMI SDS of +0.5 ± 0.1, after a mean period of 29.7 ± 22.6 months). In 11 responders, measured REE divided by predicted REE increased with +8.9%. Thirteen patients (68.4%) reported decreased hyperphagia, improvement of energy level and/or behavior during treatment. Two patients developed hypertension during treatment, which resulted in dosage adjustment or discontinuation of treatment. Twelve children continued treatment at last moment of follow-up. CONCLUSION: In addition to supportive lifestyle interventions, dextroamphetamine treatment may improve BMI in children with HO. Furthermore, dextroamphetamines have the potential to decrease hyperphagia and improve resting energy expenditure, behavior, and energy level. In patients with acquired HO, these effects seem to be more pronounced when compared to patients with congenital HO. Future studies are needed to support these results

Personal recovery suits us all: A study in patients with non-affective psychosis, unaffected siblings and healthy controls

Personal recovery transcends illness and is a unifying human experience. Core elements in personal recovery are hope, meaning, and rebuilding oneself. Here we aim to investigate whether factors associated with personal recovery in patients with non-affective psychosis, unaffected siblings and healthy controls are similar. We investigated the association between personal recovery and resilience, social support, socio-demographic and illness-related variables in 580 patients, 630 siblings, and 351 healthy controls who participated in the Genetic Risk and Outcome of Psychosis (GROUP) study. Bi-variate associations between personal recovery and individual variables were assessed and multiple linear regression analyses were performed to estimate the proportion of variance in personal recovery that could be accounted for by the predictors and to investigate which predictors independently added to the model. Positive self was significantly and independently associated with personal recovery in all three groups. Pro-active action taking also seems to be important. Social functioning significantly contributed to explained variance in patients and siblings. Regarding illness-related factors, depressive symptoms had impact on personal recovery in both patients and siblings, whereas positive symptoms only did in siblings. The findings imply that not only personal recovery itself, but also some associated factors are universally human and suit us all. This means that patients and non-patients share supportive factors of personal recovery which may help to reach mutual understanding. Recovery-oriented practices and mental health services might be more effective when focusing also on improving self-image, functional coping styles and generating social interaction, next to the reduction of affective symptoms

Low-frequency observations of the Giant Radio Galaxy NGC 6251

We present LOFAR observations at 150 MHz of the borderline FRI/FRII giant radio galaxy NGC 6251. This paper presents the most sensitive and highest resolution images of NGC 6251 at these frequencies to date, revealing for the first time a low-surface-brightness extension to the northern lobe, and a possible backflow associated with the southern lobe. The integrated spectra of components of NGC 6251 are consistent with previous measurements at higher frequencies, similar to results from other LOFAR studies of nearby radio galaxies. We find the outer structures of NGC 6251 to be either at equipartition or slightly electron dominated, similar to those of FRII sources rather than FRIs, but this conclusion remains tentative because of uncertainties associated with the geometry and the extrapolation of X-ray measurements to determine the external pressure distribution on the scale of the outer lobes. We place lower limits on the ages of the extension of the northern lobe and the backflow of the southern lobe of t ≳ 250 Myr and t ≳ 210 Myr, respectively. We present the first detection of polarization at 150 MHz in NGC 6251. Taking advantage of the high Faraday resolution of LOFAR, we place an upper limit on the magnetic field in the group of BB/10kpc)−0.5μG for a coherence scale of ΛBBμG~forΛB=240 kpc

Temporal trends in acute adrenal insufficiency events in children with congenital adrenal hyperplasia during 2019-2022

Background It is unclear whether targeted monitoring of acute adrenal insufficiency (AI) related adverse events (AE) such as sick day episodes (SDE) and hospitalisation rate in congenital adrenal hyperplasia (CAH) is associated with a change in the occurrence of these events. Aim Study temporal trends of AI related AE in the I-CAH Registry. Methods In 2022, data on the occurrence of AI-related AE in children aged &lt;18yrs with 21-hydroxylase deficiency CAH was compared to data collected in 2019. Results In 2022, a total of 513 children from 38 centres in 21 countries with a median of 8 children (range 1, 58) per centre had 2,470 visits evaluated over a 3-yr period (2019-2022). The median SDE per patient yr in 2022 was 0 (0, 2.5) compared to 0.3 (0, 6) in 2019 (p=0.01). Despite adjustment for age, CAH phenotype and duration of study period, a difference in SDE rate was still apparent between the two cohorts. Of the 38 centres in the 2022 cohort, 21 had also participated in 2019 and a reduction in SDE rate was noted in 13 (62%), an increase was noted in 3 (14%) and in 5 (24%) the rate remained the same. Of the 474 SDEs reported in the 2022 cohort, 103 (22%) led to hospitalisation compared to 299 of 1099 SDEs (27%) in the 2019 cohort (p=0.02). Conclusions The I-CAH Registry can be used for targeted monitoring of important clinical benchmarks in CAH. However, changes in reported benchmarks need careful interpretation and longer-term monitoring

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Non-functioning Pituitary Adenomas

Non-functioning pituitary adenomas (NFPAs) occur in a substantial proportion of the population. Non-functioning pituitary adenomas occur sporadically and seldom arise as components of familial tumour syndromes. Treatment of non-functioning pituitary adenomas depends on the clinical signs and symptoms, comorbidities and patient preferences. It is a process of shared decision making between the patient and a multidisciplinary team. Surgery is indicated when the pituitary adenoma abuts or compresses the optic chiasm and causes visual field loss or vision loss. The goal of pituitary surgery for NFPA is to prevent patients from incurring bitemporal hemianopsia or restore visual field deficits and/or double vision. In most cases, patients diagnosed with a NFPA need long-term follow-up in order to monitor for tumour growth, alterations in visual field examination, biochemical assessment of the anterior pituitary functions and hormone replacement therapy if needed. Endocrine nurses play a key role in educating patients about the aetiology of NFPA, surgical treatments and hormone replacement therapy.</p

Dextroamphetamine Treatment in Children With Hypothalamic Obesity

Introduction: Hypothalamic obesity (HO) in children has severe health consequences. Lifestyle interventions are mostly insufficient and currently no drug treatment is approved for children with HO. Amphetamines are known for their stimulant side-effect on resting energy expenditure (REE) and suppressing of appetite. Earlier case series have shown positive effects of amphetamines on weight in children with acquired HO. We present our experiences with dextroamphetamine treatment in the, up to now, largest cohort of children with HO. Methods: A retrospective cohort evaluation was performed of children with HO treated with dextroamphetamine at two academic endocrine pediatric clinics. Off-label use of dextroamphetamine was initiated in patients with progressive, therapy-resistant acquired or congenital HO. Anthropometrics, REE, self-reported (hyperphagic) behavior and energy level, and side effects were assessed at start and during treatment. Results: Nineteen patients with a mean age of 12.3 ± 4.0 years had been treated with dextroamphetamine. In two patients, ΔBMI SDS could not be evaluated due to short treatment duration or the simultaneous start of extensive lifestyle treatment. Mean treatment duration of the 17 evaluated patients was 23.7 ± 12.7 months. Fourteen patients (n = 10 with acquired HO, n = 4 with congenital HO) responded by BMI decline or BMI stabilization (mean ΔBMI SDS of -0.6 ± 0.8, after a mean period of 22.4 ± 10.5 months). In three patients, BMI SDS increased (mean ΔBMI SDS of +0.5 ± 0.1, after a mean period of 29.7 ± 22.6 months). In 11 responders, measured REE divided by predicted REE increased with +8.9%. Thirteen patients (68.4%) reported decreased hyperphagia, improvement of energy level and/or behavior during treatment. Two patients developed hypertension during treatment, which resulted in dosage adjustment or discontinuation of treatment. Twelve children continued treatment at last moment of follow-up. Conclusion: In addition to supportive lifestyle interventions, dextroamphetamine treatment may improve BMI in children with HO. Furthermore, dextroamphetamines have the potential to decrease hyperphagia and improve resting energy expenditure, behavior, and energy level. In patients with acquired HO, these effects seem to be more pronounced when compared to patients with congenital HO. Future studies are needed to support these results

We mind your step: understanding and preventing drop-out in the transfer from paediatric to adult tertiary endocrine healthcare

Introduction: Transition from paediatric to adult endocrinology can be challenging for adolescents, their families and healthcare professionals. Previous studies have shown that up to 25% of young adults with endocrine disorders are lost to follow-up after moving out of paediatric care. This poses a health risk for young adults, which can lead to serious and expensive medical acute and long-term complications. Methods: In order to understand and prevent dropout, we studied electronic medical records of patients with endocrine disorders. These patients were over 15 years old when they attended the paediatric endocrine outpatient clinic (OPC) of our hospital in 2013–2014 and should have made the transfer to adult care at the time of the study. Results: Of 387 adolescents, 131 had an indication for adult follow-up within our university hospital. Thirty-three (25%) were lost to follow-up. In 24 of them (73%), the invitation for the adult OPC had never been sent. We describe the failures in logistic processes that eventually led to dropout in these patients. Conclusion: We found a 25% dropout during transfer from paediatric to adult tertiary endocrine care. Of all dropouts, 73% could be attributed to the failure of logistic steps. In order to prevent these dropouts, we provide practical recommendations for patients and paediatric and adult endocrinologists