[Facial emotion recognition in children with attention-deficit/hyperactivity disorder]. / Reconocimiento de emociones faciales en niños con trastorno por déficit de atención/hiperactividad.

INTRODUCTION: There are difficulties in relationships that are attributed to a commitment in facial emotions recognition skills in subjects with attention-deficit/hyperactivity disorder (ADHD). The studies carried out did not always take into account the nature of the stimulus selected in pediatrics, which is important because the familiarity in faces, in terms of their physiognomic characteristics, makes it easier the recognition of the expressions. AIM: To identify the profile of recognition of emotions in pediatric subjects with ADHD, using as a stimulus photos of boys and girls. SUBJECTS AND METHODS: Analytical cross-sectional study of cases and controls. We analyzed the results obtained from 54 participants between 7 and 13 years divided into two groups: 26 in control group and 28 in ADHD group. They conducted an assessment with the Wechsler Intelligence Scale for Children (WISC-V), Conners' Continuous Performance Test II (CPT-II), and Child Affective Facial Expression set (CAFE). RESULTS: The ADHD group showed a lower performance in recognition of emotions in general, with greater difficulty in the recognition of anger, surprise and neutral expression in particular. No relationship was found between the recognition of emotions and age, sex, total intelligence quotient or CPT-II care variables. CONCLUSIONS: The subjects with ADHD present deficits in the recognition of emotions, especially in the recognition of anger, surprise and neutral expression, which could explain the difficulties in the interaction and that should be treated within the therapeutic framework.

TITLE: Reconocimiento de emociones faciales en niños con trastorno por déficit de atención/hiperactividad.Introducción. En sujetos con trastorno por déficit de atención/hiperactividad (TDAH), se observan dificultades en las relaciones interpersonales que se atribuyen a una afectación en las habilidades de reconocimiento de emociones faciales. Los estudios realizados no siempre tuvieron presente la naturaleza del estímulo seleccionado en pediatría, lo cual es fundamental porque la familiaridad en los rostros, en cuanto a sus características fisonómicas, favorece el reconocimiento de las expresiones. Objetivo. Identificar el perfil de reconocimiento de emociones en sujetos pediátricos con TDAH, utilizando como estímulo fotos de niños y niñas. Sujetos y métodos. Estudio analítico de corte transversal de casos y controles. Se analizaron los resultados obtenidos de 54 participantes de 7-13 años divididos en dos grupos: 26 en el grupo control y 28 en el grupo con TDAH. Realizaron una evaluación con la escala de inteligencia de Wechsler para niños (WISC-V), el Conners' Continuous Performance Test II (CPT-II) y el Child Affective Facial Expression set (CAFE). Resultados. El grupo con TDAH mostró un rendimiento menor en el reconocimiento de emociones en general, con mayor dificultad en el reconocimiento de enojo, sorpresa y expresión neutral en particular. No se encontró una relación entre el reconocimiento de emociones y la edad, el sexo, el cociente intelectual total o las variables de atención del CPT-II. Conclusiones. Los sujetos con TDAH presentan déficits en el reconocimiento de emociones, especialmente en el reconocimiento de enojo, sorpresa y expresión neutral, que podrían explicar las dificultades en la interacción y deberían tratarse dentro del marco terapéutico.

Multicentre surveillance study on feasibility, safety and efficacy of antifungal combination therapy for proven or probable invasive fungal diseases in haematological patients: the SEIFEM real-life combo study.

UNLABELLED: This multicentre observational study evaluated the feasibility, efficacy and toxicity of antifungal combination therapy (combo) as treatment of proven or probable invasive fungal diseases (IFDs) in patients with haematological malignancies. Between January 2005 and January 2010, 84 cases of IFDs (39 proven and 45 probable) treated with combo were collected in 20 Hematological Italian Centres, in patients who underwent chemotherapy or allogeneic haematopoietic stem cell transplantation for haematological diseases. Median age of patients was 34 years (range 1-73) and 37% had less than 18 years. Acute leukaemia was the most common underlying haematological disease (68/84; 81%). The phase of treatment was as follows: first induction in 21/84 (25%), consolidation phase in 18/84 (21%) and reinduction/salvage in 45/84 (54%). The main site of infection was lung with or without other sites. The principal fungal pathogens were as follows: Aspergillus sp. 68 cases (81%), Candida sp. six cases (8%), Zygomycetes four cases (5%) and Fusarium sp. four cases (5%). The most used combo was caspofungin+voriconazole 35/84 (42%), caspofungin + liposomal amphotericin B (L-AmB) 20/84 (24%) and L-AmB+voriconazole 15/84 (18%). The median duration of combo was 19 days (range 3-180). The overall response rate (ORR) was 73% (61/84 responders) without significant differences between the combo regimens. The most important factor that significantly influenced the response was granulocyte (PMN) recovery (P 0.009). Only one patient discontinued therapy (voriconazole-related neurotoxicity) and 22% experienced mild and reversible adverse events (hypokalaemia, ALT/AST increase and creatinine increase). The IFDs-attributable mortality was 17%. This study indicates that combo was both well tolerated and effective in haematological patients. The most used combo regimens were caspofungin + voriconazole (ORR 80%) and caspofungin + L-AmB (ORR 70%). The ORR was 73% and the mortality IFD related was 17%. PMN recovery during combo predicts a favourable outcome. CLINICAL TRIALS REGISTRATION: NCT00906633.

Guidelines for the use of long-term central venous catheter in children with hemato-oncological disorders. On behalf of supportive therapy working group of Italian Association of Pediatric Hematology and Oncology (AIEOP).

In the last 30 years, the use of long-term central venous catheters (CVC) is increased especially for children with hemato-oncological disorders. However, the use of CVC is associated to complications, as mechanical accidents, thrombosis, and infections that can determine a prolongation of hospital stay, an increase of costs, and sometimes life-threatening conditions that require urgent systemic treatment or CVC removal. CVC removal may be troublesome especially in neonates, infants, or any other "highly needed CVC patients"; in these selected cases, the prevention and treatment of CVC-related complications play a pivotal role and specific surveillance programs are crucial. While extensive literature is focused on CVC management in adults, no guidelines are available for children. To this aim, the first recommendations for the management of CVC infectious complication in pediatric age have been written after pediatric and adult literature review and collegial discussion among members of Supportive Therapy working group of Italian Association of Pediatric Hematology and Oncology. Compared to the adult age, the necessity of peripheral vein cultures for the diagnosis of CVC-related infection remains controversial in children because of the poorer venous asset and a conservative, pharmacologically focused management through CVC remains mandatory, with CVC removal to be performed only in selected cases.

A prospective 7-year survey on central venous catheter-related complications at a single pediatric hospital.

The aims of this study were to assess the incidence and risk factors of major central venous catheter (CVC)-related complications in a large cohort of children affected by oncological, hematological, or immunological diseases in a 7-year prospective observational study at a single center. Nine hundred fifteen CVCs were inserted in 748 children for a total period of 307,846 CVC-days. Overall, 298 complications were documented with a complication rate of 0.97/1,000 CVC-days: 105 mechanical complications (dislocations 0.30/1,000 CVC-days, ruptures 0.04/1,000 CVC-days), 174 infections (bloodstream infections 0.46/1,000 CVC-days, tunnel infections 0.10/1,000 CVC-days), and 19 thrombosis (0.06/1,000 CVC-days). Significant risk factors were: diagnosis of acute lymphoblastic leukemia (ALL) and age

Continuous antibiotic infusion for salvage therapy of partially implanted central venous catheter tunnel infections due to staphylococci.

Tunnel infection is an uncommon but serious complication observed in patients with partially implanted central venous catheters. International guidelines suggest that should include antibiotics and catheter removal. A success rate of only 5-20% was reported without catheter removal. We treated 13 episodes of tunnel Gram-positive bacterial infection occurring in pediatric patients with cancer or serious blood disorders with 24-hr intra-catheter antibiotic continuous infusion. This approach led to a 69% success rate. Continuous infusion might be an attractive option to treat tunnel Gram-positive bacterial infections when catheter removal might not be feasible or advisable.

Bloodstream infections in children with cancer: a multicentre surveillance study of the Italian Association of Paediatric Haematology and Oncology. Supportive Therapy Group-Infectious Diseases Section.

A one-year prospective, multicentre surveillance study on aetiology, main clinical features and outcome of bloodstream infections in children with cancer was conducted in 18 paediatric haematology centres belonging to the Italian Association for Paediatric Haematology and Oncology. A total of 191 bloodstream infections were reported during the study period. Of them, 123 (64%) occurred in neutropenic and 68 (36%) in non-neutropenic patients. Gram-positive cocci caused 45% (85/191) of the episodes, gram-negative rods 41% (78/191), and fungi 9% (18/191). The remaining 5% (10/191) of the episodes were poly-microbial infections. A total of 204 pathogens were isolated (46% gram-positive cocci; 44% gram-negative rods; and 10% fungi). The aetiologic distribution was similar among neutropenic and non-neutropenic patients. A correlation between the infection and the presence of an indwelling central venous catheter was found in 20% (23/114) of the episodes among neutropenic patients and in 55% (23/62) among non-neutropenic patients. Gram-negative micro-organisms were isolated in an unusually high proportion of catheter-related infections (48%). The overall mortality rate from any cause within 30 days from the first positive blood culture was 11%, and was higher among patients who were neutropenic at the onset of the infection than among those who were not neutropenic (15 versus 4%, P = 0.03). In addition, the mortality was significantly higher in recipients of bone marrow transplantation than in patients with acute leukaemia or solid tumour (21, 11 and 6%, respectively) and was also higher in fungaemias and poly-microbial infections (22 and 30%) than in single gram-positive and gram-negative bacteraemias (11 and 6%).

Analysis of early infectious complications in pediatric patients undergoing bone marrow transplantation.

The purpose of the present study was to analyze the characteristics of infectious complications occurring during the first 100 days after bone marrow transplantation (BMT) in a cohort of 123 pediatric patients with hematological malignancies (n = 73), solid tumors (n = 32) and nonmalignant disorders (n = 18). Fifty-eight patients received allogeneic grafts, and 65 patients an autologous transplant. Fever developed in 107 (87%) children; 82% of infectious complications occurred during the neutropenic period. Documented infection developed in 33 (31%) patients, while 74 (69%) patients had possible infection (i.e. fever of unknown origin). The incidence of bacteremia was 21%, and gram-positive cocci were the predominant pathogens; non-bacteremic microbiologically documented infection developed in 6% of patients; clinically evident infection developed in 4% of subjects. The incidence of primary febrile episodes was not significantly different between autologous and allogeneic BMT (86% vs 88%); nor did the median number of days to the onset of fever (5 days in both groups) or the median duration of fever (5 days in both groups) differ. In contrast, the frequency of secondary febrile episodes was significantly higher (P = 0.0001) in allogeneic BMT recipients (40%) than in autologous recipients (15%). The mortality rate due to infections was 2/36 (5%) for matched sibling donor BMT, and 1/13 (8%) for matched unrelated donor BMT. No deaths occurred in the 65 patients who were autografted. Invasive fungal infections accounted for 2 of the 3 infectious deaths. In conclusion, the majority of children undergoing BMT experienced at least one infectious episode; allogeneic BMT recipients were at high risk of developing secondary febrile episodes, but the overall mortality rate due to infection in the first 100 days after transplantation was low.

Italian guidelines for the management of infectious complications in pediatric oncology: empirical antimicrobial therapy of febrile neutropenia.

The Italian Association for Paediatric Haematology and Oncology prepared a guideline document aimed at unifying and rationalising as much as possible the management of febrile neutropenia in children with cancer, because of the potential impact of these procedures on hospital costs and on the development of antibiotic resistance. Before starting anti-infective therapy, at least 2 blood cultures, a throat swab, urine-culture, and cultures from any suspected infected site, should be performed. Routine chest X-rays at onset of febrile neutropenia are probably not necessary, in absence of respiratory signs. At the present time, the safer option probably remains the combination of a beta-lactam and an aminoglycoside, and treating febrile neutropenia outside of hospital should be considered an investigational approach. The choice of the most appropriated regimen for each institution should be based also on the local bacteriological statistics and patterns of bacterial resistance. Antibiotic toxicity and cost should be other important factors. Every subsequent addition or substitution of antibiotics should be based on objective signs of clinical deterioration. The only accepted empirical modification is empirical antifungal therapy, while the empirical addition of a glycopeptide antibiotic cannot be recommended.

Cryptococcal meningitis following a thrombotic microangiopathy in an unrelated donor bone marrow transplant recipient.

In patients undergoing bone marrow transplantation cryptococcosis is rarely encountered. We report a fatal case of Cryptococcus meningitis in a 12-year-old girl with acute lymphoblastic leukemia (ALL) in second remission who had a transplant from a human leukocyte antigen (HLA)-identical unrelated bone marrow donor. The conditioning regimen was thiotepa, cyclophosphamide, and total body irradiation (TBI); graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A, methotrexate, and antilymphocyte globulin (ALG). The patient experienced stage III GVHD responsive to high-dose corticosteroids. On day +54 a thrombotic microangiopathy occurred. On day +64 neurological status worsened; a brain computed tomographic (CT) scan showed hyperdense lesions suggesting fungal infection. Detection of cryptococcal antigen by latex agglutination was positive but India ink stain and culture were negative. Despite treatment with amphotericin B, 5-flucytosine, and granulocyte-macrophage colony-stimulating factor, the patient died 13 days after the diagnosis.

[Indwelling central venous catheters after discontinuation of therapy and risk of infection in children with cancer]. / Permanenza del catetere venoso centrale dopo la sospensione della terapia e rischio infettivo in bambini affetti da neoplasia.

In this retrospective study we report the incidence of CVC-related infections in a pediatric oncology population during the off therapy period. We analysed 128 children with oncologic diseases (solid tumors and leukemia), 78 boys and 50 girls, aged 1 to 21 years, who maintained the CVC in situ at least 6 months after the cessation of chemotherapeutic protocols. Seventy-eight patients had a single lumen Broviac-Hickman CVC, 8 patients had a double lumen Broviac-Hickman and 42 a implantable port device. The permanence of CVC in situ after discontinuation of treatment varied between 6 and 24 months. CVC was removed in 5 patients that presented a CVC-related infection, respectively 6, 6, 6, 7 and 10 months from discontinuation of therapy, in 85 patients because was considered no more necessary. 38 patients are still with CVC in situ; in this group 11 patients relapsed more than 6 months after discontinuation of the therapy and were analysed until the time of relapsed. The result of our study show that the incidence of CVC related infections in patients off therapy is very low. Considering the discomfort that frequent blood withdrawals cause to children and the relapse risk, we think that CVC may be maintained in situ more than 6 months after discontinuation of the therapy without risks for the patients.

Fluconazole versus amphotericin B as empirical antifungal therapy of unexplained fever in granulocytopenic cancer patients: a pragmatic, multicentre, prospective and randomised clinical trial.

Amphotericin B, despite its intrinsic servere toxicity, is the most commonly used empirical antifungal therapy in cancer patients with unexplained fever not responding to empirical antibacterial therapy. The aim of this study was to show whether fluconazole was as effective as, and less toxic than, amphotericin, with no effort made to compare the antifungal activity of the two drugs. A group of 112 persistently febrile (> 38 degrees C) and granulocytopenic (< 1000 cells/mm3) cancer patients, not receiving any absorbable antifungal antibiotic for prophylaxis, with a mean age of 27 years (range 1-73 years), undergoing chemotherapy for a variety of malignancies and with a diagnosis of unexplained fever after at least 96 h of empirical antibacterial therapy, were randomised to receive either fluconazole (6 mg/kg/day up to 400 mg/day) or amphotericin B (0.8 mg/kg/day) as empirical antifungal treatment. Patients were required to have normal chest X-rays at randomisation, no previous history of aspergillosis and negative surveillance cultures for Aspergillus. The intention-to-treat analysis showed defervescence and survival without treatment modification in 42 of 56 patients (75%) in the fluconazole group and in 37 of 56 (66%) in the amphotericin B group (P = 0.4). Duration of therapy was 6 days (95% CI = 4-8 days) in both groups. Death occurred in 3 patients (5%) in the fluconazole and in 2 (4%) in the amphotericin B group. No fungal death was documented in either group. Adverse events developed in 18 of 56 patients (32%) in the fluconazole group and in 46 of 56 (82%) in the amphotericin B group (P < 0.001). In the amphotericin B group, 5 patients had treatment discontinued because of toxicity, versus none in the fluconazole group, a difference which approached statistical significance (P = 0.06). This study shows that fluconazole is by far less toxic than amphotericin B and suggests that it might be as effective as amphotericin B, in pragmatical terms and for this specific indication. However, numbers are too small to allow definitive conclusions about efficacy, and the use of fluconazole for this indication remains experimental. Future studies should try to identify patients more at risk of fungal infections, with the aim of individualising antifungal approaches.

Clinical remission is associated with restoration of normal high-density lipoprotein cholesterol levels in children with malignancies.

1. Serum lipids and lipoprotein profiles were determined in children affected by different types of malignancies (leukaemias or lymphomas and solid tumours) both before any treatment and after remission of the disease following chemical or surgical therapy. 2. At the time of diagnosis, children bearing tumours showed hypertriglyceridaemia and reduced concentrations of plasma high-density lipoprotein cholesterol levels, the decrease being particularly prominent in patients with haematological tumours. Children bearing solid tumours displayed an increase of total cholesterol, while those with haematological cancer showed decreased phospholipid levels; low-density lipoprotein cholesterol in neoplastic patients was not significantly different from control values. High triacylglycerol and low high-density lipoprotein cholesterol levels were also evident in cancer patients divided according to age into three groups (0-5, 6-10 and 11-15 years) when compared with age-matched control subjects. Similarly, high triacylglycerol and low high-density lipoprotein cholesterol levels were also observed in both male and female children when patients were divided according to sex and compared with corresponding controls. 3. Clinical remission after therapy was accompanied by an increase of high-density lipoprotein cholesterol levels compared with values observed at diagnosis. In contrast, post-treatment levels of triacylglycerol were higher than those observed before therapy. These results support the hypothesis that alterations of high-density lipoprotein cholesterol levels may be related, at least in part, to the rate of tumour growth, while modifications of triacylglycerol levels may be mediated by different mechanisms.

[Pulmonary complications after bone marrow transplantation]. / Complicanze polmonari dopo trapianto di midollo osseo.

Pulmonary toxicity occurs in approximately 10 to 50% of patients undergoing bone marrow transplantation (BMT). Bacterial pneumonia very commonly affects patients within the first 6 months post-BMT. Etiologic factors include neutropenia and the presence of graft-versus-host disease (GVHD). Pulmonary fungal infections, due to candida and aspergillus, may develop in 16% of patients receiving BMT, with a high mortality rate, being about 80%. A prolonged neutropenia as well as GVHD and associated immunosuppressive treatments are important factors in predisposing a patient to develop fungal pneumonitis. Interstitial pneumonitis occurs in 10-40% of patients; herpes viruses are the most commonly documented cause, with cytomegalovirus (CMV) being the most common pathogen. No causative organism is identified in up to 60% of the cases. It is likely that some of these cases may result from drug or radiation toxicity. Lung shielding and fractionation of the dose have decreased the incidence of interstitial pneumonitis to less than 5%. Patients with GVHD are predisposed to lung infections because of the immunosuppression that accompanies GVHD and its treatment. In addition, GVHD itself appears to have a direct effect on pulmonary epithelium. Cultural and serologic studies as well as radiographic investigations and other diagnostic procedures (ie bronchoalveolar lavage) are needed for appropriate management of pulmonary complications.

[The leukemia-lymphoma syndrome with gastrointestinal involvement in childhood. A case report]. / Sindrome leucemia-linfoma con interessamento gastrointestinale in età pediatrica. Descrizione di un caso.

The gastrointestinal tract is an uncommon site of presentation for acute lymphoblastic leukemia in children. We report a child who developed a leukemia-lymphoma syndrome with central nervous system and gastrointestinal tract involvement at the diagnosis. The patient received an intensive combination chemotherapy and is currently off-therapy in continuous complete remission 29 months after the diagnosis.

Imipenem use in serious childhood infections.

Imipenem plus cilastatin is a beta-lactam antibiotic with a broad spectrum and good tolerance. For this its use is indicated in serious infections even in children. The authors carried out a preliminary bacteriological study in patients affected by serious infection, cystic fibrosis, tumors, neutropenia, subjects undergoing intensive therapy and those with abdominal surgical infection. Isolated microorganism sensitivity in these patients, towards imipenem was very high (89%-100%). With these premises, 35 patients with serious infections in various locations were treated only with imipenem. Of these, 15 were oncologic neutropenic and 20 normal. In the first group therapeutic success was 66.6% and in the second one 80%. Local and systemic tolerance always showed good results.