Context Daily growth hormone (GH) injections can be burdensome for patients and carers. Somapacitan is a long-acting, reversible albumin-binding GH derivative in development for once-weekly administration in patients with growth hormone deficiency (GHD). Objective The objective of this study is to evaluate the efficacy, safety, and tolerability of once-weekly somapacitan vs once-daily GH. Design REAL 3 is a multicenter, randomized, controlled, double-blind (somapacitan doses), phase 2 study with a 26-week main and 26-week extension phase (NCT02616562). Setting This study took place at 29 sites in 11 countries. Patients Fifty-nine GH treatment-naive prepubertal children with GHD were randomly assigned; 58 completed the trial. Interventions Interventions comprised 3 somapacitan doses (0.04 [n = 16], 0.08 [n = 15], or 0.16 mg/kg/wk [n = 14]) and daily GH (0.034 mg/kg/d [n = 14]), administered subcutaneously. Main Outcome Measures The primary end point was height velocity (HV) at week 26. Secondary efficacy end points included HV SD score (SDS) and insulin-like growth factor-I (IGF-I) SDS. Results At week 26, mean (SD) annualized HV for the somapacitan groups was 8.0 (2.0), 10.9 (1.9), and 12.9 (3.5) cm/year, respectively, vs 11.4 (3.3) cm/year for daily GH; estimated treatment difference (somapacitan 0.16 mg/kg/week—daily GH): 1.7 [95% CI –0.2 to 3.6] cm/year. HV was sustained at week 52, and significantly greater with somapacitan 0.16 mg/kg/week vs daily GH. Mean (SD) change from baseline in HV SDS at week 52 was 4.72 (2.79), 6.14 (3.36), and 8.60 (3.15) for the somapacitan groups, respectively, vs 7.41 (4.08) for daily GH. Model-derived mean (SD) IGF-I SDS for the somapacitan groups was −1.62 (0.86), −1.09 (0.78), and 0.31 (1.06), respectively, vs −0.40 (1.50) observed for daily GH. Safety and tolerability were consistent with the profile of daily GH. Conclusions In children with GHD, once-weekly somapacitan 0.16 mg/kg/week provided the closest efficacy match with similar safety and tolerability to daily GH after 26 and 52 weeks of treatment. A short visual summary of our work is available (1).

The depiction of blood vessels at the subsegmental level lacked accuracy when compared with operative findings.

1 Vasoconstrictor responses of the isolated and perfused canine epicardial coronary artery to uridine 5'-triphosphate (UTP) were analysed pharmacologically. 2 At basal perfusion pressure, UTP induced vasoconstriction in a dose-related manner and the vasoconstriction was sometimes followed by a slight vasodilatation at large doses (more than 10 nmol). The rank order of potency for vasoconstriction was UTP=UDP4ATP4TTP5ITP44 UMP. At raised perfusion pressure by 20 mM KCl, the vasoconstriction was not changed and a small vasodilatation was induced at large doses. The rank order of potency for vasodilatation was induced at large doses. The rank order of potency for vasodilatation was ATP44ITP5UDP4UTP5TTP. The maximal vasodilator response to UTP was much less than that to ATP. UMP did not induce vasodilatation. 3 The P2X receptor agonist and desensitizing agent a,b-methylene ATP (1 mM) and the P2 receptor antagonist suramin (100 mM) inhibited the vasoconstrictor responses to ATP but not those to UTP and UDP. The P2 receptor antagonist reactive blue 2 (30 mM) did not inhibit the vascular responses to UTP. 4 UTP (200 mM) desensitized the vasoconstrictor responses to UTP, but not either the vasodilator responses to UTP or the vasoconstrictor responses to ATP and UDP. UDP (200 mM) did not desensitize the vascular responses to UTP. 5 Preincubating the UDP stock solution and arterial preparation with hexokinase (10 and 1 uml 71 , respectively) did not change the vasoconstrictor responses to UDP. 6 The Ca channel blocker diltiazem (1 mM) inhibited the vasoconstrictor responses to UTP but not those to ATP and UDP. Incubation in a Ca 2+ -free solution containing 1 mM EGTA inhibited the vascular responses to ATP, UTP and UDP. 7 Removal of the endothelium by an intraluminal injection of saponin (1 mg) inhibited the vasodilator responses to UTP. Indomethacin, a cyclo-oxygenase inhibitor (1 mM), inhibited the vasodilator responses to UTP, but N G -nitro-L-arginine, a nitric oxide synthase inhibitor (300 mM), did not have an inhibitory e ect. 8 The results suggest that (1) UTP induces vasoconstriction via UTP-preferring P2Y receptors on the smooth muscle and vasodilatation via receptors di erent from those mediating the vasoconstriction induced by UTP and mediating the vasodilatation by ATP on the endothelium, through mainly the release of prostacyclin in the canine epicardial coronary artery; (2) UDP induces vasoconstriction via UDP-preferring P2Y receptors; and (3) L-type Ca ion channels are involved in the vasoconstriction induced by UTP, but not in that induced by UDP.

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We treated an 11-year-old girl with spinal cord compression near an epidural tumor. Bone marrow examination confirmed the diagnosis of acute lymphoblastic leukemia (ALL). To reduce the compression we treated her immediately with high-dose dexamethasone and vincristine administered intravenously along with local irradiation. Three days later, radiation was discontinued because magnetic resonance imaging showed that the spinal cord compression was reduced. Complete remission has continued without evidence of neurologic sequelae for more than 3 years since diagnosis. Rapid reduction of the blasts resulted in tumor lysis syndrome, which was treated with conventional management and additional diuresis without hemodialysis. Epidural spinal cord compression in childhood ALL can be treated effectively with systemic chemotherapy and local radiotherapy without laminectomy.