Prognostic factors of overall survival in children and adolescents enrolled in dose-finding trials in Europe: An Innovative Therapies for Children with Cancer study

ObjectivesDose-finding trials are fundamental to develop novel drugs for children and adolescents with advanced cancer. It is crucial to maximise individual benefit, whilst ensuring adequate assessment of key study end-points. We assessed prognostic factors of survival in paediatric phase I trials, including two predictive scores validated in adult oncology: the Royal Marsden Hospital (RMH) and the MD Anderson Cancer Center (MDACC) scores.MethodsData of patients with solid tumours aged <18 years at enrolment in their first dose-finding trial between 2000 and 2014 at eight centres of the Innovative Therapies for Children with Cancer European consortium were collected. Survival distributions were compared using log-rank test and Cox regression analyses.ResultsOverall, 248 patients were evaluated: median age, 11.2 years (range 1.0–17.9); 46% had central nervous system (CNS) tumours and 54% extra-CNS tumours. Complete responses were observed in 2.1%, partial responses in 7.2% and stable disease in 25.9%. Median overall survival (OS) was 6.3 months (95% confidence interval, 5.2–7.4). Lansky/Karnofsky ≤80%, no school/work attendance, elevated creatinine and RMH score ≥1 correlated with worse OS in the multivariate analysis. The RMH and MDACC scores correlated with OS in adolescents (12–17 years), p = 0.002, but not in children (2–11 years).ConclusionsPerformance status of 90–100% and school/work attendance at enrolment are strong indicators of longer OS in paediatric phase I trials. Adult predictive scores correlate with survival in adolescents. These findings provide a useful orientation about potential prognosis and could lead in the future to more paediatric-adapted eligibility criteria in early-phase trials.     

Primary Aldosteronism: A New Understanding

Primary aldosteronism (PAL) may always have a genetic basis. This leads to either abnormally regulated, increased biosynthesis (Familial Hyperaldosteronism Type I, FHI) or to unrestrained hyperplasia and neoplasia, usually benign. The distinction between diffuse hyperplasia, nodular hyperplasia and adenoma may be relatively unimportant in functional and etiological terms. The genetic basis must be understood before diagnosis of disease (FHI) or of predispostion (all other PAL) can be made at birth and appropriate surveillance commenced. The natural history of PAL other than FHI is for a progressive increase in severity, with both adrenals eventually involved. Long-term follow-up of PAL is therefore mandatory, and postoperative assessment of residual non-suppressible aldosterone production by fludrocortisone suppression testing useful in defining biochemical cure or improvement, and the need for specific medical treatment.     

Out-of-Hospital Cardiac Arrest –Optimal Management

Out-of-hospital cardiac arrest (OHCA) has attracted increasing attention over the past years because outcomes have improved impressively lately. The changes for neurological intact outcomes has been poor but several areas have achieved improving survival rates after adjusting their cardiac arrest care. The pre-hospital management is certainly key and decides whether a cardiac arrest patient can be brought back into a spontaneous circulation. However, the whole chain of resuscitation including the in-hospital care have improved also. This review describes aetiologies of OHCA, risk and potential protective factors and recent advances in the pre-hospital and in-hospital management of these patients.     

Effects of combination of zinc and vitamin A supplementation on serum fasting blood sugar,insulin, apoprotein B and apoprotein A-I in patients with type I diabetes

Background and aim There is accumulating evidence that shows the metabolism of zinc and vitamin A are altered in diabetes mellitus type I (DMTI), thus the present study was conducted to evaluate the effects of combination of zinc and vitamin A supplementation on serum fasting blood sugar (FBS), insulin, apoprotein B and apoprotein A-I in patients with DMTI.

Design Forty-eight, 7-year-old to 20-year-old patients with at least 2 years of DMTI history, without any metabolic condition or medicine intake with insulin treatment, participated in a randomized double-blind clinical trial for 12 weeks. They were divided into zinc and vitamin A (VAZ)-supplemented (10 mg elemental zinc per day and one-half of a 25,000 IU vitamin A tablet every other day) and/or placebo groups after matching for sex, age and DMTI duration. Nutrient intake was estimated using 24 h recall and was analyzed by food processor program. Serum apoproteins B and A-I, FBS and insulin levels were determined at the beginning and end of the trial.

Results There was significant increase in apoprotein A-I (P <?0.0001) and a significant decrease in apoprotein B (P <?0.0001) and apoprotein B/apoprotein A-I ratio (P <?0.0001) at the end of the study compared with baseline values in the VAZ group but apoprotein A-I had a significant increase (P <?0.0001) and the apoprotein B/apoprotein A-I ratio had a significant decrease (P = 0.02) at the end of study in the VAZ group compared with the control group

Conclusion It seems that combined zinc and vitamin A supplementation can improve serum apoprotein A-I, apoprotein B and the apoprotein B/apoprotein A-I ratio in patients with DMTI.     

Classic Osborn waves and incessant ventricular fibrillation in severe hypothermia

Abstract

Cardiac arrhythmias in severe hypothermia are common and are managed primarily by re-warming techniques. A 64-year-old male presented with alcohol associated aspiration pneumonia, sepsis and severe hypothermia and was noted to have classic ECG changes of hypothermia, i.e. Osborn waves. The patient had a tumultuous clinical course with prolonged resuscitative measures. Ultimately, an early focus on invasive core temperature re-warming with cardio-pulmonary bypass resulted in a favorable outcome.     

Seat-Belt-Related Injuries to the Supra-Aortic Arteries

Five seat-belt-related injuries occurring in four adults are reported. One injury involved the common carotid artery, two the internal carotid and two the subclavian arteries. Three of the four injured persons were asymptomatic and one had delayed-onset symptoms; none suffered stroke. There was no operative mortality or morbidity. Overall, the functional results of arterial reconstruction were good, with satisfactory patency at follow-up averaging 15 months.     

病毒性心肌炎患儿血清CK—MB与心肌肌钙蛋白I的检测诊断价值

目的研究血清肌酸激酶同工酶（CK—MB）与心肌肌钙蛋白I（cTnI）检测在病毒性心肌炎患儿诊断中的价值。方法将39例病毒性心肌炎患儿作为观察组，以同期行常规体检的39例健康儿童作为对照组，对比两组的cTnI、CK—MB的检测结果，并在观察组内对比cTnI与CK—MB的阳性率。结果观察组患儿发病1～2d时cTnI与CK—MB与对照组均有显著差异：发病7d及14d时观察组cTnI与对照组有显著差异。观察组内患儿发病1～2d时cTnI检测阳性率明显高于CK—MB；7d与14d时cTnI检测的阳性率则显著高于CK—MB．结论cTnI在病毒性心肌类的诊断中均且有较高的特异唐与敏威唐     

Is the knowledge of contact force beneficial in pulmonary vein antrum isolation?

Objective: To investigate the effect of the operator knowing the real-time contact force (CF) on the efficacy of pulmonary vein antrum isolation (PVAI).

Methods: Fifty patients with paroxysmal atrial fibrillation (AF) or short lasting persistent AF were randomized to CF guided PVAI (n?=?25) or conventional PVAI (n?=?25). In the CF guided group, CF between 10 and 40?g was aimed at. Efficacy of PVAI was measured as reduction in AF burden (AFB) and time to AF recurrence detected by implantable cardiac monitor (ICM), inserted three months before PVAI. Blanking period was three months and follow-up 12 months.

Results: All pulmonary veins were isolated in the CF guided group and all but one in the conventional group. Mean CF was 25?g in the CF guided group and 24?g in the conventional group (p?=?0.75). Compared to pre-ablation, median [IQR] relative reduction in AFB 3–12 months after ablation was 100 [99–100]% in the CF guided group (p?p?p?=?0.09). Nine patients (36%) had AF recurrence in the CF guided group and 13 (52%) in the conventional group (p?=?0.21, log-rank test). CF differed between operators. When adjusted for operator by regression analysis, patients without recurrent AF had lower proportion of ablation time with CF <10?g than recurrent patients (p?=?0.034). No complications occurred.

Conclusions: Operator knowledge of real-time CF had no significant effect on AFB reduction or time to AF recurrence. Larger trials should be done to study benefit of real-time CF.