Recent studies have shown that an artificial-pancreas system can improve glucosecontrol and reduce nocturnal hypoglycemia. However, it is not known whether suchresults can be replicated in settings outside the hospital. In this multicenter, multinational, randomized, crossover trial, we assessed the shortterm safety and efficacy of an artificial pancreas system for control of nocturnal glucose levels in patients (10 to 18 years of age) with type 1 diabetes at a diabetes camp. In two consecutive overnight sessions, we randomly assigned 56 patients to receive treatment with an artificial pancreas on the first night and a sensor-augmented insulin pump (control) on the second night or to the reverse order of therapies on the first and second nights. Thus, all the patients received each treatment in a randomly assigned order. The primary end points were the number of hypoglycemic events(defined as a sensor glucose value of (63 mg per deciliter [3.5 mmol per liter] for at least 10 consecutive minutes), the time spent with glucose levels below 60 mg per deciliter (3.3 mmol per liter), and the mean overnight glucose level for individual patients. On nights when the artificial pancreas was used, versus nights when the sensor augmented insulin pump was used, there were significantly fewer episodes of nighttime glucose levels below 63 mg per deciliter (7 vs. 22) and significantly shorter periods when glucose levels were below 60 mg per deciliter (P = 0.003 and P = 0.02, respectively, after adjustment for multiplicity). Median values for the individual mean overnight glucose levels were 126.4 mg per deciliter (interquartilerange, 115.7 to 139.1 [7.0 mmol per liter; interquartile range, 6.4 to 7.7]) with the artificial pancreas and 140.4 mg per deciliter (interquartile range, 105.7 to 167.4[7.8 mmol per liter; interquartile range, 5.9 to 9.3]) with the sensor-augmented pump. No serious adverse events were reported. Patients at a diabetes camp who were treated with an artificial-pancreas system had less nocturnal hypoglycemia and tighter glucose control than when they were treated with a sensor-augmented insulin pump.
COBISS.SI-ID: 1271980
This study aimed to describe the long-term outcome and immunological status of children born to mothers with antiphospholipid syndrome, to determine the factors responsible for childhood abnormalities, and to correlate the child's immunological profile with their mothers. Methods A prospective follow-up of a European multicentre cohort was conducted. The follow-up consisted of clinical examination, growth data, neurodevelopmental milestones and antiphospholipid antibodies (APL) screening.Children were examined at 3, 9, 24 months and 5 years. 134 children were analysed (female sex in 65 cases, birth weight 3000+/-500 g, height 48+/-3 cm). Sixteen per cent had a preterm birth ((37 weeks; n=22), and 14% weighted less than 2500 g at birth (n=19). Neonatal complications were noted in 18 cases (13%), with five infections (4%). During the 5-year follow-up, no thrombosis or systemic lupus erythematosus (SLE) was noted. Four children displayed behavioural abnormalities, which consisted of autism, hyperactive behaviour, feeding disorder with language delay and axial hypotonywith psychomotor delay. At birth lupus anticoagulant was present in four (4%), anticardiolipin antibodies (ACL) IgG in 18 (16%), anti-2 glycoprotein-I (anti-2GPI) IgG/M in 16 (15%) and three (3%), respectively. ACL IgG and anti-Ž2GPI disappeared at 6 months in nine (17%) and nine (18%), whereas APL persisted in 10% of children. ACL and anti-2GPI IgG were correlated with the same mother's antibodies before 6 months of age (p(0.05). Conclusion Despite the presence of APL in children, thrombosis or SLE were not observed. The presence of neurodevelopmental abnormalities seems to be more important in these children, and could justify long-term follow-up.
COBISS.SI-ID: 658860
The International Berlin-Frankfurt-Münster Study Group conducted a prospective randomized clinical trial (ALL IC-BFM 2002) for the management of childhood acute lymphoblastic leukemia (ALL) in 15 countries on three continents. The aim of this trial was to explore the impact of differential delayed intensification (DI) on outcome in all risk groups. For this trial, 5,060 eligible patients were divided into three risk groups according to age, WBC, early treatment response, and unfavorable genetic aberrations. DI was randomized as follows: standard risk (SR), two 4-week intensive elements (protocol III) versus one 7-week protocol II; intermediate risk (IR), protocol III × 3 versus protocol II × 1; high risk (HR), protocol III × 3 versus either protocol II × 2 (Associazione Italiana Ematologia Oncologia Pediatrica [AIEOP] option), or 3 HR blocks plus single protocol II (Berlin-Frankfurt-Münster [BFM] option). At 5 years, the probabilities of event-free survival and survival were 74% (± 1%) and 82% (± 1%) for all 5,060 eligible patients, 81% and 90% for the SR (n = 1,564), 75% and 83% for the IR (n = 2,650), and 55% and 62% for the HR (n = 846) groups, respectively. No improvement was accomplished by more intense and/or prolonged DI. The ALL IC-BFM 2002 trial is a good example of international collaboration in pediatric oncology.Although the alternative DI did not improve outcome compared with standard treatment and the overall results are worse than those achieved by longer established leukemia groups, the national results have generally improved.
COBISS.SI-ID: 1232812
Cytokines may promote or inhibit disease progression in type 1 diabetes. We investigated whether systemic proinflammatory, anti-inflammatory and regulatory cytokines associated differently with fasting and meal-stimulated beta cell function in patients with longer term type 1 diabetes. The beta cell function of 118 patients with type 1 diabetes of duration of 0.75%4.97 years was tested using a standardised liquid mixed meal test (MMT). Serum samples obtained at %5 to 120 min were analysed by multiplex bead-based technology for proinflammatory (IL-6, TNF-%), anti-inflammatory (IL-1 receptor antagonist [IL-1RA]) and regulatory (IL-10, TGF-%1%3) cytokines, and by standard procedures for C-peptide. Differences in beta cell function between patient groups were assessed using stepwise multiple regression analysis adjusting for sex, age, duration of diabetes, BMI, HbA1c and fasting blood glucose. High fasting systemic concentrations of the proinflammatory cytokines IL-6 and TNF-% were associated with increased fasting and stimulated C-peptide concentrations even after adjustment for confounders (p%(%0.03). Interestingly, increased concentrations of anti-inflammatory/regulatory IL-1RA, IL-10, TGF-%1 and TGF-%2 were associated with lower fasting and stimulated C-peptide levels (p%(%0.04), losing significance on adjustment for anthropometric variables. During the MMT, circulating concentrations of IL-6 and TNF-% increased (p%(%0.001) while those of IL-10 and TGF-%1 decreased (p%(%0.02) and IL-1RA and TGF-%2 remained unchanged. The association between better preserved beta cell function in longer term type 1 diabetes and increased systemic proinflammatory cytokines and decreased anti-inflammatory and regulatory cytokines is suggestive of ongoing inflammatory disease activity that might be perpetuated by the remaining beta cells. These findings should be considered when designing immune intervention studies aimed at patients with longer term type 1 diabetes and residual beta cell function.
COBISS.SI-ID: 1304492
Concordant leukemia arises as a consequence of intraplacental spread of an initiated pre-leukemic clone from one twin to the other. Both twins carried a germline N-terminal frameshift C/EBPA mutation, a 19-base pair deletion (c.147_165del, p.Glu50fs), at the time of diagnosis of AML, both twins carried an additional identical somatic C-terminal mutation: an inframe insertion of aminoacid lysine (c.936_937dupAAG, p.313_314insLys). Twin A, also had the third mutation in C-terminal part of C/EBPA gene, somatic inframe deletion of 50 aminoacids (c.911_1060del, p.304-353del). Findings suggest that C/EBPA germline mutation predispose to the development of leukemia and that the second ‘hit’ is an acquired mutation in the remaining C/EBPA allele. We suspect that this mutation has arisen in one twin and has been intraplacentaly transferred to the other twin in utero. The interval between AML onset in our twins is considerably longer than reported elsewhere. Molecular scrutiny of the healthy monozygotic co-twin is important if the individual is considered as a bone marrow donor for a twin with leukemia.
COBISS.SI-ID: 864940