Shift from intravenous or 16% subcutaneous replacement therapy to 20% subcutaneous immunoglobulin in patients with primary antibody deficiencies.

In patients with primary antibody deficiencies, subcutaneous administration of IgG (SCIG) replacement is effective, safe, well-tolerated, and can be self-administered at home. A new SCIG replacement at 20% concentration (Hizentra®) has been developed and has replaced Vivaglobin® (SCIG 16%). An observational prospective multi-centric open-label study, with retrospective comparison was conducted in 15 Italian centers, in order to investigate whether and to what extent switching to Hizentra® would affect frequency of infusions, number of infusion sites, patients' satisfaction, and tolerability in patients previously treated with Vivaglobin® or intravenous immunoglobulins (IVIG). Any variations of dosage, frequency and duration of the infusions, and of number of infusion sites induced by Hizentra® with respect to the former treatment were recorded. Practical advantages and disadvantages of Hizentra®, with respect to the medicinal product formerly used, and the variations in patients' therapy-related satisfaction were monitored by means of the TSQM (Treatment Satisfaction Questionnaire for Medication); number, frequency, and duration of infectious events and adverse effects were recorded. Eighty-two patients switched to Hizentra®: 19 (23.2%) from IVIG and 63 (76.8%) from Vivaglobin®. The mean interval between infusions was not affected by the shift (7.0 ± 2.0 days with previous treatment versus 7.1 ± 1.2 during Hizentra®). A decrease in the number of infusion sites with Hizentra® was recorded in 12 out of 56 patients for whom these data were available. At 6 months, 89.7% of patients were satisfied with Hizentra®; no difference in terms of effectiveness, side effects, convenience, and global satisfaction was observed. No difference in the incidence of adverse events was reported.

Chronic immune thrombocytopenia in childhood.

Chronic thrombocytopenias are pathological conditions defined as a persistent platelet count below the normal range for more than 6-12 months, clinically characterized by mucocutaneous bleeding. Recently, an International Working Group of expert clinicians has redefined standard terminology and definitions of primary and secondary chronic immune thrombocytopenia (ITP). A document issued on acute childhood idiopathic thrombocytopenic purpura (AIEOP) provides parents and physicians with guidelines for the management of chronic ITP and gives prominence to the periodic re-evaluation of differential diagnosis. The majority of chronic ITP children do not require pharmacological treatments, especially if symptoms are absent or minimal and the treatment decision depends on several factors, in particular clinical conditions rather than platelets count. The recommendations distinguish three therapeutic strategies: emergency or symptomatic treatment, maintenance therapy and treatment aiming at definitive remission. Experimental/off-label treatment of chronic ITP are reported in the literature, such as the use of rituximab. Currently, other drugs (thrombopoiesis stimulating factors, mycophenolate, dapsone, danazol, azathioprine, rFVIIa, cyclophosphamide, vinca alkaloids and cyclosporine) are recommended in special cases or trials.

Does NADPH oxidase deficiency cause artery dilatation in humans?

NADPH oxidase is known to modulate the arterial tone, but the role of its specific subunits is still unclear. The objective of this study was to compare the role of p47 and gp91phox (NOX2) on artery dilatation. We conducted a multicenter study enrolling 30 patients with chronic granulomatous disease (CGD) (25 with NOX2 deficiency and 5 with p47(phox) deficiency) and 30 healthy subjects (HS), matched for gender and age, in whom flow-mediated dilation (FMD), serum activity of NOX2 (soluble NOX2-derived peptide [sNOX2-dp]), urinary isoprostanes (8-iso-PGF2α), and platelet production of isoprostanes and NOX2 were determined. Compared to HS, patients with CGD had significantly higher FMD and lower sNOX2-dp and 8-iso-PGF2α levels. Compared to patients with NOX2 deficiency and HS, patients with p47(phox) hereditary deficiency had intermediate FMD and oxidative stress, that is, higher and lower FMD and lower and higher isoprostanes compared to HS and patients with NOX2 deficiency, respectively. In agreement with this finding, an ex vivo study showed higher inhibition of NOX2 activity and lower isoprostane formation in platelets from patients with NOX2 deficiency compared to platelets from ones with p47(phox) deficiency. Our observations lead to the hypothesis that oxidants are implicated in artery vasoconstriction.

Association of interleukin-(IL)10 haplotypes and serum IL-10 levels in the progression of childhood immune thrombocytopenic purpura.

Derangement of genetic and immunological factors seems to have a pivotal role in the pathophysiology of immune thrombocytopenic purpura (ITP). We investigated interleukin(IL)-10 genetically determined expression in children with an acute progression of ITP (n=41) compared to young patients with chronic ITP (n=44) and healthy controls (n=60), and attempted to correlate IL-10 production with the course of the disease. We genotyped our study population for three single nucleotide polymorphisms at positions -1082 (A/G), -819 (C/T) and -592 (C/A) in the promoter region of the IL-10 gene. IL-10 levels were measured by enzyme-linked immunoassay. The IL-10 production in our study population was significantly higher in patients carrying the GCC haplotype than those bearing ACC and ATA haplotypes (6.9 ± 1.5 vs 3.6 ± 0.8 vs 3.3 ± 0.3, p=0.03). The serum concentration of IL-10 was significantly higher in patients with an acute course of their disease, who mainly carried the GCC haplotype (92%), compared to chronic subjects, bearing the non-GCC haplotypes, and controls [17 pg/mL (1.7-18) vs 3.5 pg/mL (0.6-11) vs 3 pg/mL (1-7), p<0.01)]. Our findings show that patients carrying the GCC-high producer IL-10 haplotype have an acute development of ITP and that IL-10 levels might represent a useful predictive biomarker of the disease course.

Clinical and laboratory characteristics of children positive for antiphospholipid antibodies.

BACKGROUND: It is difficult to estimate the actual prevalence of antiphospholipid syndrome (APS) in the paediatric population since there are no standardised criteria. We aimed to assess clinical and laboratory characteristics of a cohort of children positive for antiphospholipid antibodies (aPL) to contribute to the understanding of the heterogeneous aPL-related features in childhood. MATERIALS AND METHODS: Forty-four patients with prolonged activated partial thromboplastin time were enrolled and assigned to group I ("transiently positive") or group II ("persistently positive"), based on the detection of elevated aPL plasma levels [lupus anticoagulant (LA), anticardiolipin (aCL), and anti-ß2-glycoprotein I (anti-ß2GPI) antibodies] on, respectively, one or more occasions, at least 12 weeks apart, by standard procedures. The clinical history and symptoms of all patients were recorded. RESULTS: Thirty-three (75%) patients were assigned to group I, while the other 11 (25%) formed group II. Major associated diseases in group I were urticarial vasculitis (21%), acute infections (18%) and thalassaemia (12%). Five subjects (15%) were asymptomatic. Four out of the 11 subjects (36%) in group II had thrombotic events; they were all persistently aPL-positive and two of them had concomitant systemic lupus erythematosus. The rate of detection of LA-positivity was not significantly different between the two groups (76% vs 91%, p>0.05), whereas the percentage of patients positive for overall aCL was higher in group II than in group I (54% vs 42%, respectively; p<0.05). Specifically, aCL IgG and anti-ß2GPI IgM subtypes were significantly more represented in group II than in group I (100% vs 62% and 75% vs 33%, respectively; p<0.05). DISCUSSION: Our study shows that aPL-positive children have different features that should be taken into account in the classification of criteria for paediatric APS.

Clinical significance of serum cytokine levels and thrombopoietic markers in childhood idiopathic thrombocytopenic purpura.

BACKGROUND: Biological markers useful for defining children with newly diagnosed immune thrombocytopenic purpura (ITP) who are likely to develop the chronic form of the disease are partially lacking. The purpose of this study was to assess the clinical role of both immunological and thrombopoietic markers in children with ITP and correlate their levels with different disease stages. MATERIALS AND METHODS: We enrolled 28 children with ITP at the onset of their disease, who were followed-up for a whole year and divided according to whether their disease resolved within the 12 months (n=13) or became chronic (n=15), 11 subjects with chronic ITP off therapy for at least 1 month at the time of enrolment, and 30 healthy matched controls. Serum levels of T helper type 1 and 2 and T regulatory-associated cytokines, such as interferon γ, tumour necrosis factor α, interleukin (IL) 2, IL6, IL10, and thrombopoietin were measured in all children using quantitative immunoenzymatic assays, while reticulated platelets were evaluated by flow cytometric analysis. RESULTS: Serum IL10 levels were significantly higher in patients with an acute evolution of ITP than in either healthy controls (p<0.001) or patients with chronic progression of ITP (p<0.05). Reticulated platelet count and thrombopoietin levels were significantly higher in ITP patients at the onset of their disease, whether with acute resolution or chronic progression, than in healthy subjects (p<0.01; p<0.001), but did not differ between the groups of patients. CONCLUSION: IL-10 seems to predict the clinical course of ITP, as it is significantly higher at the onset of disease in patients who obtain disease remission in less than 1 year.

Venous thrombosis in children: an emerging issue.

More and more cases of venous thrombosis are diagnosed in children thanks to newer imaging modalities. Central venous catheters have become commonplace in the care of critically ill children and have contributed to the increased rate of thrombotic events. Lastly, children who develop life-threatening or chronic medical conditions are surviving longer because of advanced medical therapies; these intensive therapies can be complicated by events such as thrombosis. Over the last 10 years, specific guidelines for treating thrombosis in children have become available. Nevertheless, in many situations anticoagulant treatment is specially tailored to each individual patient's needs. Some new antithrombotic drugs which have undergone clinical testing in adults might be beneficial to paediatric patients with thromboembolic disorders; unfortunately, clinical data and reports on the use of these drugs in children, when available, are extremely limited. The aim of this review is to provide physicians with enough background information to be able to manage thrombosis in children. First, by helping them detect a thrombotic event in a child. Upon confirmation of the diagnosis, the physician will request the appropriate tests and will choose the best treatment on the basis of the guidelines and recommendations. Moreover, the paediatrician will have the information he or she needs to identify which children are at highest risk of acute thrombotic events and relevant long-term sequelae and, therefore, to decide on the appropriate prophylactic or pharmacologic strategy. Lastly, we would like to provide the paediatrician with information on future drugs with regard to the treatment and prophylaxis of thrombosis.

Metabolic, inflammatory, endothelial and haemostatic markers in a group of Italian obese children and adolescents.

Childhood obesity and its related comorbidities are increasingly recognised in children, predisposing them to early cardiovascular disease and metabolic syndrome. The objective of the study was to investigate markers of metabolism, inflammation and haemostasis in a group of Italian obese children and adolescents. Fifty-nine obese and 40 non-obese subjects were recruited. Fasting glucose and insulin, total cholesterol, HDL and LDL cholesterol, triglycerides, high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor alpha (TNF-α), and adiponectin were measured. Hypercoagulability was assessed by measuring the circulating levels of thrombin-antithrombin complex (TAT), D: -dimer, fibrinogen, plasminogen activator inhibitor 1 (PAI-1) and von Willebrand Factor (vWF). A significant degree of insulin resistance was present in obese subjects compared with controls (p < 0.0001). The obese showed higher levels of total cholesterol, LDL cholesterol and triglycerides, and lower levels of HDL cholesterol than controls (p < 0.0001). Circulating levels of hsCRP and TNF-α were significantly higher in obese than in controls while serum adiponectin levels were significantly lower in obese than non-obese subjects (p < 0.001; p = 0.031; p < 0.0001, respectively). vWF, TAT, D-dimer, fibrinogen and PAI-1 levels were significant higher in obese subjects compared with control group (p = 0.02; p < 0.0001; p = 0.0037; p < 0.0001; p = 0.017, respectively). In conclusion, our results suggest that childhood obesity per se is associated with a proinflammatory and prothrombotic state.

Effect of eradication of Helicobacter pylori in children with chronic immune thrombocytopenia: a prospective, controlled, multicenter study.

BACKGROUND: The eradication of Helicobacter pylori has been associated with remission of immune thrombocytopenia (ITP) in approximately half of eradicated patients. Data on children are limited to small case series. PROCEDURE: Children from 16 centers in Italy, who were less than 18 years of age and diagnosed with chronic ITP (cITP), were screened for H. pylori infection. Positive patients underwent standard triple therapy with amoxicillin, clarithromycin, and omeprazole. The eradication response was defined as follows: complete response, platelet (PLT) count ≥ 150 × 10(9) /L; partial response, PLT count of at least 50 × 10(9) /L; no response, PLT count <50 × 10(9) /L. RESULTS: Of 244 screened patients, 50 (20%) had H. pylori infection, 37 of which received eradication therapy and completed follow-up. Eradication was successful in 33/37 patients (89%). PLT recovery was demonstrated in 13/33 patients after eradication (39%), whereas spontaneous remission was observed in 17/166 (10%) H. pylori-negative patients (P < 0.005). Responders more often required second line eradication (9/13), whereas a second cycle was required in 3/20 non-responders (P < 0.005). CONCLUSIONS: Among the large cohort of patients, those who underwent successful H. pylori eradication showed a significantly higher PLT response. Therefore, it may be appropriate to look for H. pylori and eventually eradicate it in children with cITP.

Prospective study of hemostatic alterations in children with acute lymphoblastic leukemia.

In a group of newly diagnosed acute lymphocytic leukemia (ALL) children we evaluated a number of hemostatic and inflammatory markers at diagnosis and at different time points during chemotherapy for the remission induction to identify alterations in the plasma levels of prothrombotic markers before and during the course of chemotherapy. The following plasma markers were evaluated: thrombin-antithrombin complex (TAT), D-Dimer, plasminogen activator inhibitor 1 (PAI-1), antithrombin, fibrinogen, von Willebrand factor (VWF) antigen and high molecular weight VWF (HMW-VWF) multimers, P-selectin, tumor necrosis factor alpha (TNF-alpha), and interleukin 6 (IL-6). Plasma samples were collected at the following time points: at T0 (baseline) and T1 (+24 days of therapy), T2 (+36 days therapy), and T3 (+64 days therapy). The results show that, at diagnosis, ALL children presented with laboratory signs of increased thrombin generation and fibrin formation (i.e. high TAT and D-dimer levels), fibrinolysis inhibition (i.e. high PAI-1 level), endothelial activation (i.e., high HMW-VWF and soluble P-selectin levels) and inflammation (i.e. high TNF-alpha and IL-6 levels). After starting induction therapy, the thrombin generation markers and inflammatory cytokines significantly decreased. To the opposite, PAI-1 and P-selectin significantly increased, suggesting an insult by chemotherapy on the vascular endothelium. These effects were more evident during steroid administration. Symptomatic venous thromboembolism (VTE) episodes developed in two cases during induction therapy, which did not allow the evaluation of the predictive value for VTE of laboratory markers.

Effectiveness of recall systems for improving influenza vaccination coverage in children with oncohematological malignancies.

In order to verify whether a telephone recall system directly managed by the pediatricians who usually follow up the children for their cancer, with influenza vaccine administered in the oncological clinic, is more effective than an anonymous recall system, 205 children with oncohematological malignancies were randomised to one of three intervention strategies for increasing influenza vaccination coverage. The results showed that all of the strategies were useful in increasing influenza vaccination coverage, but the efficacy of recall was optimal only in the children who had completed chemotherapy since less than six months.

Management of chronic childhood immune thrombocytopenic purpura: AIEOP consensus guidelines.

BACKGROUND/OBJECTIVE: The management of chronic childhood idiopathic thrombocytopenic purpura (ITP) is distinct from acute ITP. Similar to the publication on acute ITP guidelines, the AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica) considered it appropriate to develop consensus guidelines for chronic childhood ITP to provide useful and shared information for physicians, healthcare professionals, parents and patients. DESIGN/METHODS: A preliminary, evidence-based document issued by a select group of AIEOP pediatric hematologists was discussed, modified and approved during a Consensus Conference according to procedures previously validated by the AIEOP Board. RESULTS: The guidelines give prominence to the periodical reevaluation of all the etiological hypotheses of thrombocytopenia in relation to its clinical condition. The majority of chronic ITP children do not require treatment, especially if bleeding is absent or minimal. The treatment decision depends on several factors other than the platelet count, and treatment options are suggested in relation to the therapeutic scenarios. Recommendations are given regarding support for surgery, particular hemorrhagic conditions, daily activities/sports, as well as for vaccines and drugs. Experimental treatments are also discussed.

Impact of influenza-like illness and effectiveness of influenza vaccination in oncohematological children who have completed cancer therapy.

In order to evaluate the impact of influenza-like illness and the effectiveness of influenza vaccination in children with oncohematological disease who have completed cancer therapy, 182 children with a diagnosis of oncohematological disease were divided into two subgroups on the basis of the length of time off therapy (<6 months or 6-24 months) and randomised 1:1 to receive influenza vaccination or not. The controls were 91 otherwise healthy children unvaccinated against influenza. The results show that the clinical and socioeconomic impact of influenza-like illnesses and the effectiveness of influenza vaccination in oncohematological children who have completed cancer therapy are related to the length of the off therapy period, and seem to be significantly greater in those who have been off therapy for less than 6 months in comparison with healthy controls. This suggests that the administration of influenza vaccination should be strongly recommended only among oncohematological children who have been off therapy for less than 6 months.

Association between DEFB1 gene haplotype and herpes viruses seroprevalence in children with acute lymphoblastic leukemia.

Recent studies investigated the role of an unusual immune response to infective agents in the etiology of acute lymphoblastic leukemia (ALL) in children. Human beta-defensin-1 (hBD-1) is an anti-microbial peptide of the innate immune system, which exerts a killing role against pathogens. In the present study, three polymorphisms have been genotyped, namely, -52G/A, -44C/G and -20G/A, of DEFB1 gene, coding for hBD-1, in 40 ALL patients and 40 healthy children, and tested for an association between genetic variants of the protein and seroprevalence of antibodies for herpes viruses. The seroprevalence of cytomegalovirus (CMV), herpes simplex viruses (HSV) and Epstein-Barr virus (EBV) IgG antibodies in leukemic children was higher than that in controls (CMV: 61.5 vs. 27.3%, p = .008; HSV: 50 vs. 24.2%, p = .04; EBV: 61.3 vs. 46.2%, p = ns, respectively). Carriers of the GCA haplotype were found to have a significantly higher rate of immunization against CMV and HSV in ALL children compared to controls (CMV: 68 vs. 29%, p = .006; HSV: 56 vs. 26%, p = .04, respectively). No such observation was made when we analyzed the immunization against Epstein-Barr virus (EBV) by GCA haplotype in case and controls (58 vs. 40%, p = ns). These findings suggest that leukemic patients carrying untranslated variants of hBD-1 display a higher susceptibility to herpes viruses infections than controls.

Hepatic veno-occlusive disease during chemotherapy for nephroblastoma: successful and safe treatment with defibrotide. Report of a clinical case.

Here we report a case of administration of defibrotide in an 11 months old infant with hepatic veno-occlusive disease during chemotherapy for nephroblastoma. He presented with abdominal distension, a weight gain of 15%, ascites, hepatomegaly with right upper quadrant pain, thrombocytopenia and hypertransaminasemia. Despite therapy, his clinical conditions aggravated, and, therefore intravenous administration of defibrotide on a compassionate-use basis was started. The dosage was 15 mg/kg/day in 4 divided doses, which was increased gradually (in 3 days) to 40 mg/kg/day in 4 divided doses. Defibrotide proved safe and effective in resolving clinical symptoms and normalizing serological findings in the syndrome.

Hereditary deficiency of gp91(phox) is associated with enhanced arterial dilatation: results of a multicenter study.

BACKGROUND: NADPH oxidase is believed to modulate arterial tone, but its role in humans is still unclear. The objective of this study was to evaluate whether NADPH oxidase is involved in flow-mediated arterial dilation (FMD). METHODS AND RESULTS: Twenty-five patients with hereditary deficiency of gp91(phox), the catalytic core of NADPH oxidase, (X-CGD), 25 healthy subjects, and 25 obese patients matched for sex and age were recruited. FMD, platelet gp91(phox), serum levels of nitrite and nitrate as markers of nitric oxide generation, oxidized low-density lipoprotein, and urinary excretion of isoprostanes as markers of oxidative stress were determined. Platelet gp91(phox) expression was downregulated in X-CGD patients (1.0+/-0.8 mean fluorescence; P<0.001) and upregulated in obese patients (4.1+/-2.2 mean fluorescence; P=0.01) compared with healthy subjects (2.9+/-1.7 mean fluorescence). Urinary excretion of isoprostanes was reduced in X-CGD patients (41.7+/-33.3 pg/mg creatinine; P=0.04) and increased in obese patients (154.4+/-91 pg/mg creatinine; P<0.001) compared with healthy subjects (69.5+/-52.4 pg/mg creatinine). Obese patients had higher serum oxidized low-density lipoprotein than healthy subjects (35.3+/-6.7 versus 24.8+/-9.8 U/L; P<0.001) and X-CGD patients (28.5+/-7.2 U/L; P<0.001). X-CGD patients had significantly higher FMD (14.7+/-5.9%) compared with healthy subjects (7.9+/-2.5%; P<0.001); obese patients had lower FMD (5.3+/-3.0%; P=0.028) compared with healthy subjects. Serum nitrite and nitrate levels were significantly higher in patients with X-CGD (36.0+/-10.8 micromol/L; P=0.016) and lower in obese patients (9.3+/-11.0 micromol/L; P=0.001) compared with healthy subjects (27.1+/-19.1 micromol/L). Serum nitrite and nitrate levels significantly correlated with FMD (R(s)=0.403, P<0.001) and platelet gp91(phox) (R(s)=-0.515, P<0.001). FMD inversely correlated with platelet gp91(phox) (R(s)=-0.502, P<0.001) and isoprostanes (R(s)=-0.513, P<0.001). CONCLUSIONS: This study provides the first evidence that, in humans, gp91(phox) is implicated in the modulation of arterial tone.

Effects of VEGF on phenotypic severity in children with hereditary hemorrhagic telangiectasia.

The purpose of this study was to estimate vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-beta1 serum levels in children with hereditary hemorrhagic telangiectasia (HHT) type 1 and type 2 and to correlate them to the presence of arteriovenous malformations (AVMs). High VEGF levels were initially found in an infant who had been hospitalized with intestinal bleeding and suspected HHT. This case led to the evaluation of VEGF and TGF-beta1 by standard enzyme-linked immunosorbent assay in 13 children with HHT and familiarity. Patients were divided into 2 groups on the basis of the presence/absence of pulmonary AVMs. No significant difference was found for VEGF and TGF-beta1 levels in HHT patients versus controls. Among HHT patients, serum levels of VEGF in those without AVM were significantly lower than those with AVM and normal controls. No difference for TGF-beta1 levels was found in these patient subgroups. Low VEGF levels may represent a protection factor against the onset of pulmonary AVMs in HHT children. However, neither VEGF nor TGF-beta1 can be used as biochemical markers for an early diagnosis in HHT. The diagnosis of HHT still requires clinical criteria, which permitted to confirm the presence of the disease in the infant with intestinal bleeding.

Molecular characterization of a large cohort of patients with Chronic Granulomatous Disease and identification of novel CYBB mutations: an Italian multicenter study.

Chronic Granulomatous Disease (CGD) is a rare inherited disorder in which phagocytes fail to produce antimicrobial superoxide because NADPH oxidase activity is absent. In about 65% of the cases, the disease is due to mutations affecting the X-linked CYBB gene, encoding the gp91(phox) subunit of NADPH oxidase. We investigated 34 CGD male patients by DHPLC and direct sequencing. A mutation was found in the CYBB gene of 33 patients and 9 of these were novel: one non-sense mutation (c.1123 G>T), three missense mutations (c.58G>A; c.1076 G>C; c.1357 T>A), two splice site mutations (c.141+5G>T; c.142-1G>A), one duplication (c.42_45dupCATT), one deletion (c.184delT), and one rare deletion of two non-contiguous nucleotides (c.1287delT+c.1290delC). One patient had the most frequent GT homozygous deletion in exon2 of the NCF-1 gene encoding the p47(phox) subunit of NADPH oxidase. The carrier analysis was performed in 23 patients' mothers and 16 female relatives through molecular and FISH studies. No clear correlation between the severity of clinical symptoms and the type of mutation could be demonstrated. This study further supports the great heterogeneity of the disease and the notion that genetic analysis is a critical step in obtaining a definitive diagnosis for CGD.

Successful treatment with Protein C of febrile neutropenia in pediatric patients during cancer therapy.

Febrile Neutropenia (FN) is a complication of chemotherapy in childhood cancer and at the same time secondary deficit of Protein C (PC) is often present during sepsis in children with cancer. In this study we have compared the clinical outcome of two different groups. At the onset of FN during chemotherapy the first group (patients with a secondary deficit of PC) received Protein C Concentrate (PCC) replacement while the other group without PC deficiency received only symptomatic therapies. We report that PC replacement could shorten duration of FN and improve the clinical outcome. The administration of PCC was safe and without any complications.

Factors conditioning effectiveness of a reminder/recall system to improve influenza vaccination in asthmatic children.

In order to verify whether a telephone recall system directly managed by pediatricians who usually follow up children for their asthma is more effective than an anonymous recall system, we randomly assigned 285 asthmatic children (177 males; mean age 10.3+/-3.4 years) to one of three groups: those whose mothers were to be called by a pediatrician not previously involved in caring for their asthmatic children and who received the vaccine in our immunisation clinic (group 1); those whose mothers were to be called by a pediatrician from our asthma clinic and who received the vaccine in the immunisation clinic (group 2); and those whose mothers were to be called by a pediatrician from our asthma clinic and who received the vaccine in the same clinic (group 3). Our findings highlight that the use of a reminder/recall system increases vaccination rates in asthmatic children, and show that the best results are obtained when the mothers are contacted and the vaccine administered by the pediatricians who usually follow up the child for asthma.