Context: TransCon Growth Hormone (GH) (Ascendis Pharma) is a long-acting recombinant sustained-release human GH prodrug in development for children with GH deficiency (GHD).Objective: To compare the pharmacokinetics, pharmacodynamics, safety, and efficacy of weekly TransCon GH to that of daily GH in prepubertal children with GHD. Design:Randomized, open-label, active-controlled study of three doses of weekly TransCon GH versus daily Genotropin (Pfizer).Setting: Thirty-eight centers in 14 European countries and Egypt.Patients: Prepubertal male and female treatment-naïve children with GHD (n = 53).Interventions: Subjects received one of three TransCon GH doses (0.14, 0.21, or 0.30 mg GH/kg/wk) or Genotropin 0.03 mg GH/kg/d for 26 weeks.Main Outcome Measures: GH and insulinlike growth factor-1 (IGF-1) levels, growth, adverse events, and immunogenicity.Results: Both GH maximum concentration and area under the curve were similar following TransCon GH or Genotropin administration at comparable doses. A dose response was observed, with IGF-1 standard deviation scores increasing into the normal range for all three TransCon GH doses. Annualized mean height velocity for the three TransCon GH doses ranged from 11.9 cm to 13.9 cm, which was not statistically different from 11.6 cm for Genotropin. Adverse events were mild to moderate, and most were unrelated to the study drug. Injection site tolerance was good. One TransCon GH subject developed a low-titer, nonneutralizing antibody response to GH. Conclusions:The results suggest that long-acting TransCon GH is comparable to daily Genotropin for GH (pharmacokinetics) and IGF-1 (pharmacodynamics) levels, safety, and efficacy and support advancement into phase 3 development.

Three multicenter, randomized, controlled studies evaluated doripenem in children 3 months to <18 years of age, with complicated intra-abdominal or urinary tract infections and bacterial pneumonia.In the 66 patients treated with doripenem before early termination of the studies for nonsafety reasons, doripenem was safe and generally well tolerated. Low enrollment limited ability to assess benefits and risks of doripenem in children.

Background/Aims: Diagnosis of growth hormone deficiency (GHD) in children requires the use of provocative growth hormone (GH) stimulation tests, which can have limited reliability and are potentially contraindicated in some patients. This is the first paediatric study to test the safety, tolerability, and pharmacokinetics (PK)/pharmacodynamics (PD) of macimorelin, an oral GH secretagogue, approved for diagnosis of adult GHD. Methods: In this open-label, group com-parison, single-dose escalation trial (EudraCT 2018-001988-23), sequential cohorts of patients (C1-C3) received ascending single doses of macimorelin: 0.25 (C1), 0.5 (C2), and 1.0 (C3) mg/kg. Primary endpoints were safety and tolerability, and secondary endpoints were PK/PD. Results: Twenty-four patients aged between 2 and <18 with suspected GHD participated in the study. No macimorelin-related adverse events were reported, and macimorelin was well tolerated.

CLINICAL AND ANAMNESTIC FEATURES OF THE COURSE OF ACUTE BRONCHITIS IN CHILDRENStrelkova M., Senatorova G. The purpose of the study wasto detect clinical and anamnestic features of the course of acute obstructive bronchitis in children with a background of undifferentiated connective tissue dysplasia. Dynamic examination of 42 children with acute obstructive bronchitis was performed. The registration card for all children was developed and filled, it consisted of several sections: general information, family history, allergic history, life and past medical history, phenotypic assessment of undifferentiated connective tissue dysplasia. The results indicate that compromised allergic and genealogical history, as well as burdened obstetric history of the mother (threatened preterm delivery and gestosis) is significant risk factors. Assessment of clinical manifestations of acute obstructive bronchitis in children showed that the severity of the disease, which is determined by the degree of severity and duration of symptoms, was associated with the number of signs ofUCTD.Keywords: acute obstructive bronchitis, children, undifferentiated connective tissue dysplasia, wheezing, phenotypic assessment. РезюмеКЛИНИЧЕСКИЕ И АНАМНЕСТИЧЕСКИЕ ОСОБЕННОСТИ ТЕЧЕНИЯ ОСТРОГО БРОНХИТА У ДЕТЕЙСтрелкова М., Сенаторова Г.Метою дослідження було виявити клінічні та анамнестичні особливості перебігу гострого обструктивного бронхіту (ГОБ) у дітей на тлі недиференційованої дисплазії сполучної тканини. Проведено динамічне обстеження 42 дітей з гострим обструктивним бронхітом. Розроблено і заповнено реєстраційну картку для всіх дітей, вона складалася з кількох розділів: загальна інформація, сімейний анамнез, алергологічний анамнез, анамнез життя та хвороби дитини, фенотипічні оцінки недиференційованої дисплазії сполучної тканини. Результати свідчать про наявність факторів ризику - наявність обтяженого алергологічного та генеалогічного анамнезу, а також обтяжений акушерський анамнез матері (наявність загрози передчасних пологів та гестозів). При аналізі клінічних проявів ГОБ у дітей було встановлено, що ступінь тяжкості та тривалості симптомів захворювання була пов'язана з кількістю ознак недиференційованої дисплазії сполучної тканини.Ключові слова: гострий обструктивний бронхіт, діти, недиференційована дисплазія сполучної тканини, фенотипічні ознаки. Резюме.КЛИНИЧЕСКИЕ И АНАМНЕСТИЧЕСКИЕ ОСОБЕННОСТИ ТЕЧЕНИЯ ОСТРОГО БРОНХИТА У ДЕТЕЙСтрелкова М., Сенаторова Г.Целью исследования было выявить клинические и анамнестические особенности течения острого обструктивного бронхита у детей на фоне недифференцированной дисплазии соединительной ткани. Проведено динамическое обследование 42 детей с острым обструктивным бронхитом (ООБ). Разработаны и заполнены регистрационную карточку для всех детей, она состояла из нескольких разделов: общая информация, семейный анамнез, аллергологический анамнез, анамнез жизни и болезни ребенка, фенотипическая оценка признаков недифференцированнойдисплазиисоединительной ткани. Результаты свидетельствуют о наличии факторов риска - наличие отягощенного аллергологического и генеалогического анамнеза, а также отягощенный акушерский анамнез матери (наличие угрозы преждевременных родов и гестозов). При анализе клинических проявлений ГОБ у детей было установлено, что степень тяжести и продолжительности симптомов заболевания была связана с количеством признаков признаков недифференцированнойдисплазиисоединительной ткани.Ключевые слова: острый обструктивный бронхит, дети, недифференцированная дисплазия соединительной ткани, фенотипические признаки.

Objectives GX-H9 is a long-acting form of recombinant human GH under clinical development for both adults and children with GHD. In this report, 24-month efficacy and safety of once weekly and every other week (EOW) administration of GX-H9 were evaluated, in addition to Genotropin® switch-ability to GX-H9 after 12-month of treatment. Methods Subjects were randomly assigned to receive either one of three doses of GX-H9 (0.8 mg/kg/week, 1.2 mg/kg/week or 2.4 mg/kg every other week) or 0.03 mg/kg/day of Genotropin®. Treatment duration is 24-month for all patients in GX-H9 arms while patients in Genotropin® arm were re-randomized to one of three doses of GX-H9 at the completion of the first 12-month of treatment. Doses of GX-H9 were adjusted throughout the treatment period whenever necessary, based on IGF-1 levels. Results Out of 56 randomized, 54 received either GX-H9 or Genotropin®. Fifty subjects completed the 12-month treatment period. Of 50, 45 subjects completed the next 12-month, comprising 33 patients from GX-H9 and 12 patients who switched from Genotropin®. First year/second year mean±SD annualized height velocity (aHV) for 0.8 mg/kg/week, 1.2 mg/kg/week or 2.4 mg/kg every other week of GX-H9 were 10.50±2.54/9.14±1.96, 11.76±1.96/9.88±1.92 and 11.03±2.92/9.72±1.90 cm/year, respectively. First year mean±SD aHV for Genotropin® was 9.14±3.09 cm/year. Patients switched to one of the three doses of GX-H9 in the second year showed comparable aHV in the second year (8.73±2.69/7.60±0.90/9.13±1.07 cm/year for 0.8 mg/kg/week, 1.2 mg/kg/week and 2.4 mg/kg/EOW GX-H9, respectively). No significant slow-down of the growth was observed in the second year from patients who received GX-H9 throughout and patients who switched from Genotropin®. Mean change in height SDS after 12 months/24 months of GX-H9 treatment throughout from baseline treatment improved continuously (+1.10/+1.61 and +1.31/+1.89 and +1.15/+1.69 for 0.8 mg/kg/week, 1.2 mg/kg/week and 2.4 mg/kg EOW GX-H9, respectively). First year mean change in height SDS for Genotropin® was +0.92 SDS, and showed comparable improvement in height SDS after switching to GX-H9 weekly arms (+0.76 and +0.79 SDS for 0.8 mg/kg/week and 1.2 mg/kg/week, respectively). Most treatment-emergent adverse events were evaluated as unrelated to the study drug and were mild or moderate in severity. No new safety concerns were observed throughout 24 months of long-term GX-H9 treatment or after switching to GX-H9 from Genotropin®.Conclusions Growth response and safety profile of GX-H9 in children with GHD is comparable to those of daily GH, achieving robust growth rates after 24-month treatment. Subjects switched from Genotropin® in the second year, also showed substantial catch-up growth indicated by improvement in height SDS. GX-H9 has a unique potential to be a convenient long-term GH providing not only weekly but also twice-monthly treatment.

The aim of the study to evaluate the peculiarities of the aortic wall structure at the place of coarctation. Materials and methods: Studying of the aortic sections removed during operative correction at the place of constriction. 10 children at the age between 1 to 6 months were undergone the operation. Intraoperative aortic biopsy specimens were observed in 10% neutral formalin. Histologic sections were prepared in a conventional way followed by staining them with hematoxylin-eosin. Results: Histological examination in the areas of constriction revealed that the endothelium in all the preparations had poor expressiveness. The most significant changes were recorded in the middle layer of the aorta in the form of reduced development of elastic fibers, their fragmentation and chaotic arrangement. Angiomatosis with the formation of thin-layer small vessels by capillary type was found out. In all the preparations, areas of emptying of cells and fibers of the middle cover with the formation of cystic structures were revealed. Conclusions: The histological examination has revealed changes in the structure of the aorta wall, which may indicate the systemic nature of the lesion and make it possible to consider coarctation of the aorta to be a manifestation of systemic vasculopathy. The above-mentioned facts determine the need for a more detailed examination of children with the specified pathology at different stages of observation.

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