Copeptin: Utility in Paediatric Patients with Hyponatraemia.

INTRODUCTION: Copeptin concentrations are a useful component of the diagnostic workup of paediatric patients with polyuria and polydipsia, but the value of measuring copeptin in patients with hyponatraemia is less clear. CASE REPORTS: We report 5 children with hyponatraemia in the context of different underlying pathologies. Copeptin concentrations were elevated in 4 cases (13.7, 14.4, 26.1, and 233 pmol/L; reference range 2.4-8.6 pmol/L), suggesting that non-osmoregulated vasopressin release (syndrome of inappropriate antidiuretic hormone) was the underlying mechanism for low sodium levels. In one of the patients, there was an underlying diagnosis of Schaaf-Yang syndrome (MAGEL2 gene mutation) with a clinical picture suggestive of dysregulated vasopressin production with inappropriately high and then low copeptin release. In one hyponatraemic patient, low copeptin concentrations indicated that non-osmoregulated arginine vasopressin release was not the cause of hyponatraemia and oliguria. DISCUSSION: Copeptin measurement did not influence management acutely but helped to clarify the mechanism leading to hyponatraemia when the result was available. Relatively high and low copeptin concentrations in association with hypo- and hypernatraemia indicate dysregulated vasopressin production in Schaaf-Yang syndrome.

Problem solving in clinical practice: the sick infant with low sodium and high potassium.

Many paediatricians will be faced with a sick infant who on investigation is found to have hyponatraemia and hyperkalaemia at some time in their career. The focus of initial management includes the treatment of potentially life-threatening hyperkalaemia with concurrent investigation aiming to elucidate whether the underlying cause reflects a primarily renal or endocrine pathology. We describe the presentation of two infants who each presented with one of the more common underlying diagnoses that led to this biochemical disturbance and discuss the approach to immediate treatment, diagnostic work-up and longer term management.

The potential role of the eGFR in differentiating between true and pseudohyperkalaemia.

BACKGROUND: Differentiating between true and pseudohyperkalaemia is essential for patient management. The common causes of pseudohyperkalaemia include haemolysis, blood cell dyscrasias and EDTA contamination. One approach to differentiate between them is by checking the renal function, as it is believed that true hyperkalaemia is rare with normal function. This is logical, but there is limited published evidence to support it. The aim of this study was to investigate the potential role of the estimated glomerular filtration rate in differentiating true from pseudohyperkalaemia. METHODS: GP serum potassium results >6.0 mmol/L from 1 January 2017 to 31 December 2017, with a repeat within seven days, were included. Entries were retrospectively classified as true or pseudohyperkalaemia based on the potassium reference change value and reference interval. If the initial sample had a full blood count, it was classified as normal/abnormal to remove blood cell dyscrasias. Different estimated glomerular filtration rate cut-points were used to determine the potential in differentiating true from pseudohyperkalaemia. RESULTS: A total of 272 patients were included with potassium results >6.0 mmol/L, with 145 classified as pseudohyperkalaemia. At an estimated glomerular filtration rate of 90 ml/min/1.73 m2, the negative predictive value was 81% (95% CI: 67-90%); this increased to 86% (95% CI: 66-95%) by removing patients with abnormal full blood counts. When only patients with an initial potassium ≥6.5 mmol/L were included (regardless of full blood count), at an estimated glomerular filtration rate of 90 ml/min/1.73 m2, the negative predictive value was 100%. Lower negative predictive values were seen with decreasing estimated glomerular filtration rate cut-points. CONCLUSION: Normal renal function was not associated with true hyperkalaemia, making the estimated glomerular filtration rate a useful tool in predicting true from pseudohyperkalaemia, especially for potassium results ≥6.5 mmol/L.

Adult height in patients with familial male-limited precocious puberty and the role of an aromatase inhibitor in patient management.

BACKGROUND: There is little adult height data in patients with familial male-limited precocious puberty (FMPP) and no management consensus. We assessed the treatment and adult height in local patients with FMPP and those reported in the literature. METHODS: Growth data were obtained on four local patients with FMPP and a search performed to obtain management details and adult height data on cases in the literature. UK (90) population standards were used to calculate standard deviation scores (SDS). RESULTS: Adult height data were available on 25 men with FMPP of whom 21 were treated. Median adult height SDS of patients was -1.5 SD with a mid-parental target of -0.6 SD (p=0.1). Eight patients (32%) had an adult height above the mid-parental target and seven patients (28%) had a height >2 SD below the mean. The median height SD was -0.03 in untreated patients and +0.5 SD in those receiving an aromatase inhibitor. There was no relationship between height and age at presentation. CONCLUSIONS: Aromatase inhibitor therapy is associated with a positive height outcome in FMPP but the outcome with and without intervention is unpredictable. Clinicians need to be cautious when counselling families about the potential height outcome in FMPP.

Acceptance of a reusable self-injection device for recombinant human growth hormone: final data from a questionnaire-based, cross-sectional, international, multicenter, observational study in pediatric patients.

BACKGROUND: A questionnaire-based survey was conducted to assess attitudes toward a reusable self-injection system (SurePal™) among pediatric patients with growth disturbances who were prescribed treatment with Omnitrope(®) within routine clinical practice. METHODS: This was a multicenter, observational study, incorporated into the noninterventional PAtients TReated with Omnitrope(®) (PATRO) Children study. Included subjects, or their caregivers, completed a questionnaire on the following five main areas: attractiveness of SurePal™, training received, using the device, the low drug wastage system, and experience versus other devices used previously (pretreated patients). Responses were based on a 5-point scale, with 2 being the best possible outcome and -2 the worst possible outcome. RESULTS: In total, 550 patients were included in this study (338 from France, 169 from Germany, and 43 from the UK). The mean age ± standard deviation of participants was 10.8±3.5 years; the majority (57%) were male and growth hormone treatment naïve (88%). Almost half (49.8%) of children prepared their SurePal™ for injection themselves and 45.5% performed injections themselves. As patients progressed into their teens, the majority (≥75%) favored preparing SurePal™ and performing injections themselves, rather than seeking assistance. The attractiveness of SurePal™ was rated as excellent/good by 84.7% of patients overall; this rating was similarly high (≥79%) across countries and age-groups. Preparing (88.8%) and using (83.3%) SurePal™ were rated as very easy/easy by most patients; these ratings were similarly high, irrespective of country or age-group. The dose-memory function was rated as very helpful/helpful by 66.2% of patients. Among 246 patients who reported using the low drug-waste feature, 87.4% found it helpful. Among pretreated patients (n=64), 78.2% reported that SurePal™ was much better/better than their previous device. CONCLUSION: These data confirm the ease of use and patient preference for SurePal™ among pediatric patients with growth disturbances.

Testosterone Treatment of Pubertal Delay in Duchenne Muscular Dystrophy.

BACKGROUND: The outlook for adolescents with Duchenne muscular dystrophy (DMD) has improved greatly as a result of corticosteroid use, but treatment will compromise growth and delay puberty. Whether exogenous testosterone can promote growth, development, and skeletal health is unclear. METHODS: We collected data retrospectively on growth and pubertal response in 14 adolescents with DMD who were treated with testosterone between 2008 and 2014. RESULTS: A total of 14 boys were treated at a median age of 14.5 years. Eight have finished treatment after a mean age of 3.1 years and the feedback from families was generally positive. The mean testicular volume pretreatment was 2.4 and 3.9 mL posttreatment. The mean baseline testosterone concentrations were < 1.0 and 5.4 nmol/L postintervention. Median height velocity increased from 0.45 cm/y before treatment to 3.6 cm/y after the treatment. The mean height gain was 14.2 cm. CONCLUSIONS: A broad range of testosterone preparations was used. Testosterone was generally well-liked, but side effects were experienced by some patients and the pubertal growth increment appears to be compromised. Few subjects had adult endogenous testosterone levels posttreatment. Controlled studies are required to determine the most appropriate treatment regimen and the precise impact of testosterone on key outcomes, such as muscle function and bone integrity. Clinicians will then be better placed to advise families about likely benefits and risks.

Acceptability of the reusable SurePal™ self-injection device for Omnitrope(®) among pediatric patients: results from a questionnaire-based, cross-sectional, multicenter observational study.

BACKGROUND: SurePal™ is a reusable self-injection system that has been developed to support daily administration of Omnitrope(®) (Sandoz, Kundl, Austria). A questionnaire-based cross-sectional survey was conducted to evaluate acceptability of, and preference for, SurePal™ in pediatric patients who were prescribed treatment with Omnitrope(®) within routine clinical care. METHODS: This multicenter, observational study was incorporated into the ongoing non-interventional PATRO (PAtients TReated with Omnitrope(®)) Children study. Patients (or caregivers) were provided with a questionnaire that included five main topics; attractiveness of the device, training received, using SurePal™, the low drug wastage system, and experience versus other devices used previously (where applicable). Questions were scored on a 5-point scale, with -2 being the worst possible outcome (eg, very hard/very poor) and 2 being the best possible outcome (eg, very easy/excellent). RESULTS: A total of 186 patients were included in this study (Germany, n=154; UK, n=32). The attractiveness of SurePal™ was rated as excellent/good by 87.1% of patients. Overall, 86.5% of patients found that using their SurePal™ was very easy/easy. Almost all patients (96.2%) found that preparing their SurePal™ for injection was very easy/easy, and 89.2% found that injecting with SurePal™ was very easy/easy. 85.5% of patients recorded that the dose memory function was helpful, and 87.6% that taking their SurePal™ apart after an injection was very easy/easy. Of the 88 patients who recorded that they had used the low drug waste feature, 89.8% found the feature to be helpful. Among pre-treated patients (n=42), 81% recorded that SurePal™ was much better/better than their previously used device. CONCLUSION: This questionnaire-based cross-sectional survey in pediatric patients confirms the ease of use and patient preference for SurePal™, a reusable self-injection system that has been developed to support daily administration of Omnitrope(®).

The use of cell-delivered gene therapy for the treatment of HIV/AIDS.

HIV/AIDS is a disease that impairs immune function, primarily by decreasing T-lymphocyte count. Its progression can be contained by highly active antiretroviral therapy (HAART), but there are side effects that can be severe, and the development of resistance often forces the physician to modify the HAART regimen. There are no vaccines available for HIV. An alternative approach that could provide a path to a curative therapy is the use of cell-delivered gene therapy in which an anti-HIV gene(s) is introduced into hematopoietic cells to produce a population that is protected from the effects of HIV. In this paper, we review the field and discuss an approach using a short hairpin RNA to CCR5, an important co-receptor for HIV.

The impact of fasting and treatment omission on susceptibility to hypoglycaemia in children and adolescents with GH and cortisol insufficiency.

OBJECTIVE: Hypoglycaemia may be a frequent occurrence in young GH deficient patients and so we studied the response to fasting in children and adolescents with GH and/or cortisol deficiency. METHODS: A total of 20 patients (2-18 years) fasted for 14 h (22.00-12.00 h) on two occasions as part of a randomized cross-over study. Fourteen had pituitary hormone deficiency (PHD) including GH deficiency (GHD). Of the 14 patients, seven were ACTH sufficient (PHDC+) and seven ACTH deficient (PHDC-). Six had primary adrenal failure (PAF). Subjects administered or omitted their normal dose of evening GH and/or morning hydrocortisone. Glucose, insulin, GH, cortisol, ketones and catecholamines were measured at 04.00 h and regularly from 07.00 to 12.00 h. Insulin sensitivity was assessed by HOMA and hypoglycaemia defined as a blood glucose (BG)

Analysis of prognostic factors of acute lymphoblastic leukemia in infants: report on CCG 1953 from the Children's Oncology Group.

Infant acute lymphoblastic leukemia (ALL) has a poor therapeutic outcome despite attempts to treat it based on prognostic factor-guided therapy. This is the first cooperative group trial characterizing all infants at the molecular level for MLL/11q23 rearrangement. All infants enrolled on Children's Cancer Group (CCG) 1953 were tested for MLL rearrangement by Southern blot and the 11q23 translocation partner was identified (4;11, 9;11, 11;19, or "other") by reverse-transcriptase polymerase chain reaction (PCR). One hundred fifteen infants were enrolled; overall event-free survival (EFS) was 41.7% (SD = 9.2%) and overall survival (OS) was 44.8% at 5 years. Five-year EFS for MLL-rearranged cases was 33.6% and for MLL-nonrearranged cases was 60.3%. The difference in EFS between the 3 major MLL rearrangements did not reach statistical significance. Multivariate Cox regression analyses showed a rank order of significance for negative impact on prognosis of CD10 negativity, age younger than 6 months, and MLL rearrangement, in that order. Toxicity was the most frequent cause of death. Relapse as a first event in CCG 1953 was later (median, 295 days) compared with CCG 1883 historic control (median, 207 days). MLL/11q23 rearrangement, CD10 expression, and age are important prognostic factors in infant ALL, but molecular 11q23 translocation partners do not predict outcome.