Emergency management in patients with haemophilia A and inhibitors on prophylaxis with emicizumab: AICE practical guidance in collaboration with SIBioC, SIMEU, SIMEUP, SIPMeL and SISET.

Emicizumab has been approved in several countries for regular prophylaxis in patients with congenital haemophilia A and FVIII inhibitors because it substantially reduces their bleeding risk and improves quality of life. However, although significantly less frequent, some breakthrough bleeds may still occur while on emicizumab, requiring treatment with bypassing or other haemostatic agents. Thrombotic complications have been reported with the associated use of activated prothrombin complex concentrates. In addition, when surgery/invasive procedures are needed while on emicizumab, their management requires multidisciplinary competences and direct supervision by experts in the use of this agent. Given this, and in order to expand the current knowledge on the use of emicizumab and concomitant haemostatic agents, and reduce the risk of complications in this setting, the Italian Association of Haemophilia Centres (AICE) here provides guidance on the management of breakthrough bleeds and surgery in emergency situations in patients with haemophilia A and inhibitors on emicizumab prophylaxis. This paper has been shared with other National Scientific Societies involved in the field.

Increased nerve growth factor serum levels in top athletes.

OBJECTIVE: The nerve growth factor (NGF) is the main neurotrophin, which, besides being an important growth factor for nerves, plays an important role as a mediator of inflammation. Nerve growth factor has been shown to increase in relation to stress stimuli and in allergic diseases in humans as well as after physical exercise in animal models. This study aims at evaluating NGF serum levels in top athletes, a population sample in which allergic and neuro-immune diseases are reported with a significantly increased prevalence. DESIGN: Observational, cross-sectional, multicenter study. SETTING: Institutional, tertiary care. PARTICIPANTS: Ninety-six Italian pre-Olympic athletes (44 allergic and 52 nonallergic) and 49 matched controls selected within the Italian National Olympic delegation (n = 435). INDEPENDENT VARIABLES: Nerve growth factor serum levels determined through an enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Parametric or nonparametric tests were used for comparing NGF serum levels among different study groups depending on value distributions. RESULTS: Nerve growth factor serum levels were significantly higher in athletes than in controls independently from the presence of allergy. Nerve growth factor mean values were 368.3 ± 776.3 pg/mL in the sample of athletes and 174.1 ± 483.7 pg/mL in the control group (P < 0.001). CONCLUSIONS: This is the first study showing that intense and prolonged physical exercise is associated with an increase of NGF serum levels in athletes. Whether the increased NGF production might be linked to the prevalent Th2 response observed in allergic diseases and after physical exercise and whether it might be related to the patophysiology of neuro-immune disorders as such amyotrophic lateral sclerosis, reported with a higher prevalence in athletes, should deserve further investigations.

Iron and ADHD: time to move beyond serum ferritin levels.

OBJECTIVE: (a) To compare serum ferritin levels in a sample of stimulant-naïve children with ADHD and matched controls and (b) to assess the association of serum ferritin to ADHD symptoms severity, ADHD subtypes, and IQ. METHOD: The ADHD and the control groups included 101 and 93 children, respectively. Serum ferritin levels were determined with the enzyme-linked immunosorbent assay method. RESULTS: Serum ferritin did not significantly differ between children with ADHD and controls, as well as among ADHD subtypes. Correlations between serum ferritin levels and measures related to IQ or ADHD severity were not significant. CONCLUSION: This is the largest controlled study that assessed ferritin levels in stimulant-naïve ADHD children. The findings of this study do not support a significant relationship between serum ferritin levels and ADHD. However, the authors' results based on peripheral measures of iron do not rule out a possible implication of brain iron deficiency in ADHD, grounded on neurobiological hypotheses and preliminary empirical evidence.

AQUA: Allergy Questionnaire for Athletes. Development and validation.

PURPOSE: Despite the high and increasing prevalence of allergic diseases in athletes, allergy diagnostics is not part of the routine medical examination in sports medicine. This study reports the development and validation of an easy and reliable questionnaire for screening allergy in athletes. METHODS: AQUA was derived from the European Community Respiratory Health Survey Questionnaire. On the basis of open interviews with team doctors, coaches, and athletes, questions were added about: the type, duration, and intensity of training; exercise-related allergic and infectious symptoms; social habits (smoking); drug and food supplements intake; antidoping regulations. The final version of the questionnaire, made of 25 selected questions, was validated in 128 professional soccer players who underwent accurate history taking, medical examination, skin prick testing, and/or specific IgE determination. On the basis of the correlation with objective allergy (positive skin tests to at least one allergen), questions were scored from 1 to 5 according to their positive likelihood ratio. RESULTS: Skin tests (gold standard for validation) were positive in 46.8% of soccer players. Mean total AQUA score was 9.4 +/- 7.8 in allergic athletes versus 1.3 +/- 2.3 in nonallergic athletes. A total AQUA score of >or=5 was shown to have the best positive predictive value for allergy (0.94) with a specificity of 97.1% and a sensitivity of 58.3%. CONCLUSIONS: AQUA, produced in 10 European languages, is a validated, easy, and reliable tool for calling attention on the high prevalence of allergy in athletes.