Simplified radius,ulna, and short bone‐age assessment procedure using grouped‐Tanner‐Whitehouse method

Background: The Tanner–Whitehouse III (TW3) method is popular for assessing children's bone age, but it is time‐consuming in clinical settings; to simplify this, a grouped‐TW algorithm (GTA) was developed. Methods: A total of 534 left‐hand roentgenograms of subjects aged 2–15 years, including 270 training and 264 testing datasets, were evaluated by a senior pediatrician. Next, GTA was used to choose the appropriate candidate of radius, ulna, and short bones and to classify the bones into three groups by data mining. Group 1 was composed of the maturity pattern of the radius and the middle phalange of the third and fifth digits and three weights were obtained by data mining, yielding a result similar to that of TW3. Subsequently, new bone‐age assessment tables were constructed for boys and girls by linear regression and fuzzy logic. In addition, the Bland–Altman plot was utilized to compare accuracy between the GTA, the Greulich–Pyle (GP), and the TW3 method. Results: The relative accuracy between the GTA and the TW3 was 96.2% in boys and 95% in girls, with an error of 1 year, while that between the assessment results of the GP and TW3 was about 87%, with an error of 1 year. However, even if the three weights were not optimally processed, GTA yielded a marginal result with an accuracy of 78.2% in boys and 79.6% in girls. Conclusions: GTA can efficiently simplify the complexity of the TW3 method, while maintaining almost the same accuracy. The relative accuracy between the assessment results of GTA and GP can also be marginal.     

Hemophagocytic lymphohistiocytosis: Pathogenesis,diagnosis, and management

Hemophagocytic lymphohistiocytosis (HLH) is a life‐threatening hyperinflammatory syndrome that is classified into primary and secondary HLH. Primary HLH consists of monogenic disorders that mainly affect the perforin‐mediated cytotoxicity of cytotoxic T lymphocytes and natural killer cells. Secondary HLH occurs as a complication in various settings such as infection, malignancy, autoimmune disease, and post‐allogeneic hematopoietic stem cell transplantation. Both primary and secondary HLH are characterized by uncontrolled hypercytokinemia that results in myelosuppression and vascular endothelium damage. More than 10% of patients with HLH die within 2 months of diagnosis due to bleeding in the visceral organs, opportunistic infection due to neutropenia, or multiple organ failure. The most obvious presentations of HLH are persistent fever refractory to antimicrobial agents and hyperferritinemia due to hypersecretion of various cytokines. The first rule is not to overlook signs of hypercytokinemia and to settle the hyperactivated immunological state as soon as possible. In addition, to improve outcome, it is essential to identify the disorders underlying HLH and provide disorder‐appropriate treatment.     

Analysis of clinical and molecular characteristics of Wiskott–Aldrich syndrome in 24 patients from 23 unrelated Chinese families

Zhang Z‐Y, Xiao H‐Q, Jiang L‐P, Zhou Y, Zhao Q, Yu J, Liu W, Yang X‐Q, Zhao X‐D. Analysis of clinical and molecular characteristics of Wiskott–Aldrich syndrome in 24 patients from 23 unrelated Chinese families.
Pediatr Allergy Immunol 2010: 21: 522–532.
© 2010 John Wiley & Sons A/S The clinical data of 24 children with Wiskott–Aldrich syndrome (WAS) from 23 unrelated Chinese families were reviewed in the present study. WAS protein (WASP) expression in peripheral blood mononuclear cells was examined by flow cytometry (FCM); WASP gene was amplified by PCR and directly sequenced to analyze mutations in the WASP gene in patients and their female relatives. FCM analysis of 21 patients showed that 18 cases were WASP‐negative, and three had partially WASP expression. WASP gene analysis revealed mutations in 23 patients, including five missense mutations, four nonsense mutations, four deletion mutations, three insertion mutations, six splice site mutations, and one complex mutation, among which, 20 unique mutations were detected, including seven novel mutations (168 C>A, 747–748del T, 793–797del C, 1185 ins C, Dup 1251–1267, 1277 insA and 1266 C>G; 1267–1269del C). Five WAS children underwent stem cell transplantation. After 2 months of transplantation, WASP expression was restored to normal in all five patients whereas one patient died of cytomegalovirus‐induced interstitial lung disease. WASP gene analysis can make a definite diagnosis of WAS and identify mutation carriers, beneficial for timely treatment and genetic counseling for children with WAS.     

Pharmacokinetic and prandial pharmacodynamic properties of insulin degludec/insulin aspart in children,adolescents, and adults with type 1 diabetes

Insulin degludec/insulin aspart (IDegAsp) is a soluble coformulation of long‐acting insulin degludec and short‐acting insulin aspart. This open‐label, Phase 1 study aimed to determine the pharmacodynamic and pharmacokinetic properties of IDegAsp in children (6–11 yr), adolescents (12–17 yr), and adults (18–65 yr) with type 1 diabetes mellitus (T1DM). Thirty‐eight subjects received single subcutaneous IDegAsp dosing (0.5 U/kg) immediately before a standardized liquid meal (17.3 g carbohydrates/100 mL; adjusted for body weight) followed by plasma glucose (PG) and pharmacokinetic blood sampling for 36 and 57 h, respectively. There were no apparent differences between age groups in PG lowering effect (AUC_{PG baseline,0–6 h,meal,SD}), maximum PG excursion (ΔPG_max,meal,SD), or maximum PG concentration (PG_max,meal,SD) after the standardized meal. Estimated ratios (ERs) for total exposure (AUC_{IAsp,0–12 h,SD}) and maximum concentration (C_max,IAsp,SD) of IAsp in IDegAsp were children/adults, 1.69 (95% confidence interval, CI: 1.02; 2.80) and 1.66 (95% CI: 1.10; 2.51); adolescents/adults, 1.14 (95% CI: 0.76; 1.69) and 1.16 (95% CI: 0.84; 1.61). ERs for total exposure (AUC_{IDeg,0–∞,SD}) and maximum concentration (C_max,IDeg,SD) of IDeg in IDegAsp were children/adults, 1.42 (95% CI: 0.94; 2.16) and 1.38 (95% CI: 1.09; 1.76); adolescents/adults, 1.23 (95% CI: 0.96; 1.58) and 1.16 (95% CI: 0.95; 1.42). IDegAsp was well tolerated across age groups. The fast onset of prandial coverage of IAsp in IDegAsp and the ultra‐long pharmacokinetic properties of IDeg in IDegAsp were preserved in children and adolescents. Exposure to IAsp and IDeg seemed to be higher in children vs. adults, but no differences were observed in PG lowering effect. IDegAsp could be an alternative treatment option in children and adolescents with T1DM.     

Congenital Rosai–Dorfman disease presenting with anemia,thrombocytopenia, and hepatomegaly

Rosai–Dorfman disease (RDD) is a rare entity of non‐Langerhans cell histiocytoses (non‐LCH) which usually presents with bilateral painless cervical lymphadenopathy. We describe a neonate with RDD who presented with anemia, thrombocytopenia and hepatomegaly. He recovered spontaneously with conservative management. This represents an atypical presentation of RDD. Conservative management with close monitoring can be adopted for some with systemic involvement. Pediatr Blood Cancer 2009;52:415–417. © 2008 Wiley‐Liss, Inc.     

Megacystis–microcolon–intestinal hypoperistalsis and prune belly: overlapping syndromes

Megacystis–microcolon–intestinal hypoperistalsis syndrome (MMIHS) is a rare, often fatal condition. Infants present with a functional obstruction of the gastrointestinal tract (GI), malrotation, microcolon, and a large nonobstructed bladder. Several features common to both MMIHS and Eagle–Barrett or prune belly syndrome (PBS) include hydronephrosis, bladder distension and laxity of the abdominal wall musculature. Additionally, MMIHS and PBS have been reported in the same family, suggesting the possibility of a common pathogenesis. MMIHS usually presents in female infants. We present a male infant diagnosed with both MMIHS and PBS. This is a unique case in which both MMIHS and true PBS are present in the same infant.     

Indoor environment,atopy and the risk of asthma in children in New Zealand

The objective of this study was to examine the relationship between the indoor environment, atopy and asthma in 7–9-year-old children. Cases and controls were randomly selected from children who participated in the International Study of Asthma and Allergies in Childhood (ISAAC) in Wellington, New Zealand. Cases were children with a previous diagnosis of asthma and current medication use (n = 233) and controls were children with no history of wheezing and no diagnosis of asthma (n = 241). Information was recorded about the indoor environment during the first year of life and currently. Dust was sampled from floors and beds and Der p 1 and Fel d 1 measured using enzyme-linked immunosorbent assays. Skin-prick tests were performed with eight common allergens. Sensitization to Dermatophagoides farinae (OR = 3.19; 95% CI 1.74–5.84), Dermatophagoides pteronyssinus (OR = 2.06; 95% CI 1.16–3.65) and cat (OR = 3.89; 95% CI 1.06–14.30) were independently associated with current asthma. The use of a sheepskin in the first year of life (OR = 1.91; 95% CI 1.11–3.33) was also independently associated with current asthma but current Der p 1 levels showed no association with current asthma. Exposures in early life may be more important than current exposures in determining asthma at age 7–9 years. Prospective studies are needed in New Zealand to determine the relative importance of early life exposures to Der p 1 and other risk factors for asthma.     

Imipenem–cilastatin versus piperacillin–tazobactam as monotherapy in febrile neutropenia

Background: In view of the recent trend toward monotherapy in the treatment of febrile neutropenia, we evaluated the clinical efficacy and safety of imipenem–cilastatin versus piperacillin–tazobactam as an empiric therapy for febrile neutropenia in children with malignant diseases. Methods: Febrile neutropenic patients received either imipenem–cilastatin or piperacillin–tazobactam randomly. Improvement without any changes in the initial antibiotic treatment was defined as “success” and improvement with modification of the initial treatment and death was defined as “failure”. Results: Over 12 months, 99 febrile neutropenic episodes were treated with monotherapy in 63 patients with a median age of 5 years. At admission, median absolute neutrophil count was 50/mm³ and in 67% of episodes, neutrophil count was under 100/mm³. Median duration of neutropenia was 5 days. In 22% of episodes, neutropenia persisted for more than 10 days. Piperacillin–tazobactam was used in 52 episodes and imipenem–cilastatin was used in 47 episodes. There was no difference between groups in terms of age, sex, primary diseases, neutrophil count or duration of neutropenia. In the whole group, the success rate was 67% and the failure rate was 33%, whereas in the piperacillin–tazobactam group, the rates were 71% and 29%; and in the imipenem–cilastatin group they were 62% and 38%, respectively (P > 0.05). There were no deaths. No major adverse effects were seen in either group. Conclusions: Although failure was slightly higher in the imipenem–cilastatin group, this was statistically insignificant. Both of these antibiotics can be used safely for initial empirical monotherapy of febrile neutropenia.