@article {10750, title = {Administering analgesia sublingually is a suitable option for children with acute abdominal pain in the emergency department.}, journal = {Acta Paediatr}, volume = {108}, year = {2019}, month = {2019 Jan}, pages = {143-148}, abstract = {

AIM: Acute abdominal pain is a frequent complaint in children attending emergency departments. The aim of this study was to investigate the pain score reductions when children with acute abdominal pain received medication sublingually.

METHODS: We carried out a multicentre randomised controlled trial in three children{\textquoteright}s hospitals in Italy between March 2015 and June 2017. Children from four to 18~years of age with acute abdominal pain were recruited if their self-reported pain was at least six on a scale from 0-10. The children were randomised to receive ketorolac 0.5~mg/kg (n~=~70) or tramadol 2~mg/kg (n~=~70) sublingually or a melt in the mouth powder of 20~mg/kg paracetamol (n~=~70). The main study outcome was the pain scores for the three drugs after two hours.

RESULTS: The 210 children (58.6\% girls) had a median age of 12~years with an interquartile range of 9-14.3. The median pain scores at two hours were not significantly different between ketorolac 2.0 (interquartile ranges, IQR 0.0-4.3) and tramadol 3.0 (IQR 1.0-5.0) vs paracetamol 3.0 (IQR 0.8-5.0). The median pain reductions were all 5.0 points.

CONCLUSION: Delivering analgesia sublingually was a suitable option for pain relief in children with acute abdominal pain in the emergency department.

}, issn = {1651-2227}, doi = {10.1111/apa.14514}, author = {Cozzi, Giorgio and Zanchi, Chiara and Chiaretti, Antonio and Tipo, Vincenzo and Cernich, Marta and D{\textquoteright}Anna, Carolina and Fantacci, Claudia and Conversano, Ester and Zanon, Davide and Ronfani, Luca and Barbi, Egidio} } @article {10766, title = {Complete Remission of a Refractory Acute Myeloid Leukemia with Myelodysplastic- and Monosomy 7-Related Changes after a Combined Conditioning Regimen of Plerixafor, Cytarabine and Melphalan in a 4-Year-Old Boy: A Case Report and Review of Literature.}, journal = {Cancers (Basel)}, volume = {10}, year = {2018}, month = {2018 Aug 27}, abstract = {

Acute myeloid leukemia with myelodysplastic changes and monosomy 7 is a rare form of pediatric leukemia associated with very poor disease-free survival. The refractoriness of the disease is due to the protection offered by the bone marrow niche, making leukemic stem cells impervious to whatever chemotherapy or myeloablative regimen is chosen. Using a mobilizing agent for haematopoietic stem cells, Plerixafor, could sensitise leukemic cells to the myeloablative therapy. This approach was not previously used in a pediatric population, and in adult populations, was used in combination with busulphan with no difference in overall survival. We describe the case of a 4-year-old boy affected by refractory acute myeloid leukemia with myelodysplastic changes and monosomy 7. The child had never achieved a remission. We proposed a combined time-scheduled scheme of therapy with plerixafor and melphalan. Combining pharmacokinetics of plerixafor with pharmacokinetics and rapid and elevated myeloablative potential of melphalan in high dosage (200 mg/m{\texttwosuperior}), we succeeded in mobilizing more than 85\% of stem blasts immediately before infusion of Melphalan. The count of residual blasts after 8 h from melphalan infusion was only 1.3 cells/μL. The child achieved an engraftment at day +32 with full donor chimerism. Sixteen months after haematopoietic stem cell transplantation (HSCT), he is well and in complete remission. Our case suggests that the use of plerixafor before a conditioning therapy with melphalan could induce remission in acute myeloid leukemia refractory to the usual conditioning therapy in pediatric patients. This work adds strength to the body of knowledge regarding the "personalized" conditioning regimen for high-risk leukemic patients.

}, issn = {2072-6694}, doi = {10.3390/cancers10090291}, author = {Grasso, Antonio G and Granzotto, Marilena and Zanon, Davide and Maestro, Alessandra and Loiacono, Stefano and Maximova, Natalia} } @article {10431, title = {Multicenter randomized, double-blind controlled trial to evaluate the efficacy of laser therapy for the treatment of severe oral mucositis induced by chemotherapy in children: laMPO RCT.}, journal = {Pediatr Blood Cancer}, volume = {65}, year = {2018}, month = {2018 Aug}, pages = {e27098}, abstract = {

OBJECTIVES: To demonstrate the efficacy of laser photobiomodulation (PBM) compared to that of placebo on severe oral mucositis (OM) in pediatric oncology patients. The primary objective was the reduction of OM grade (World Health Organization [WHO] scale) 7 days after starting PBM. Secondary objectives were reduction of pain, analgesic consumption, and incidence of side effects.

METHODS: One hundred and one children with WHO grade~>~2 chemotherapy-induced OM were enrolled in eight Italian hospitals. Patients were randomized to either PBM or sham treatment for four consecutive days (days +1 to +4). On days +4, +7, and +11, OM grade, pain (following a 0-10 numeric pain rating scale, NRS) and need for analgesics were evaluated by an operator blinded to treatment.

RESULTS: Fifty-one patients were allocated to the PBM group, and 50 were allocated to the sham group. In total, 93.7\% of PBM patients and 72\% of sham patients had OM grade~<~3 WHO on day +7 (P~=~0.01). A significant reduction of pain was registered on day +7 in the PBM versus sham group (NRS 1 [0-3] vs. 2.5 [1-5], P~<~0.006). Reduced use of analgesics was reported in the PBM group, although it was not statistically significant. No significant adverse events attributable to treatment were recorded.

CONCLUSIONS: PBM is a safe, feasible, and effective treatment for children affected by chemotherapy-induced OM, as it accelerates mucosal recovery and reduces pain.

}, issn = {1545-5017}, doi = {10.1002/pbc.27098}, author = {Gobbo, Margherita and Verzegnassi, Federico and Ronfani, Luca and Zanon, Davide and Melchionda, Fraia and Bagattoni, Simone and Majorana, Alessandra and Bardellini, Elena and Mura, Rosamaria and Piras, Alessandra and Petris, Maria Grazia and Mariuzzi, Maria Livia and Barone, Angelica and Merigo, Elisabetta and Decembrino, Nunzia and Vitale, Marina Consuelo and Berger, Massimo and Defabianis, Patrizia and Biasotto, Matteo and Ottaviani, Giulia and Zanazzo, Giulio Andrea} } @article {10852, title = {Total body irradiation and iron chelation treatment are associated with pancreatic injury following pediatric hematopoietic stem cell transplantation.}, journal = {Oncotarget}, volume = {9}, year = {2018}, month = {2018 Apr 13}, pages = {19543-19554}, abstract = {

Whereas many studies have addressed the risk of organ dysfunction following hematopoietic stem cell transplantation (HSCT), little is known about pancreatic susceptibility in this setting. We aimed to investigate the effect of iron overload (IO) and total body irradiation (TBI) on pancreatic function of children undergoing HSCT. We retrospectively evaluated children admitted between 2012-2016 fulfilling the following criteria: normal pancreatic iron concentration (PIC), regular pancreatic function before HSCT, availability of abdominal magnetic resonance imaging with gradient-recalled-echo sequences and a full set of biochemical markers of IO and pancreatic function performed before HSCT and at discharge. We divided the patients according to the use of TBI or myeloablative chemotherapy (MCHT) in the conditioning regimen. All patients with severe IO or moderate IO with a high risk of engraftment delay or transplantation-related complications underwent chelation therapy with deferoxamine (DFO) from the first day of conditioning to discharge. 63 patients had a HSCT in the study period, 13 did not fulfill the inclusion criteria; 50 (25 in each group) are included in the analysis, and did not show differences at baseline evaluation. At follow up testing the TBI group showed a significantly higher PIC (107,8{\textpm}100,3 μmol/g vs 28,4{\textpm}37,9 in MCHT group, p<0,0001). In the TBI group the patients who had DFO treatment had higher PIC (223,2{\textpm}48,8 μmol/g vs 55,7{\textpm}10,5 without DFO treatment, p<0,0001), and all patients having PIC >100 μmol/g at follow up had DFO-based chelation therapy, versus 26\% of those with lower PIC (p<0,0001). The number of patients presenting exocrine pancreatic dysfunctions one month after transplantation was significantly higher in the TBI group (48\% vs 4\%; p<0.0001). The mean pancreatic volume reduction was significantly greater in the TBI group (39,1\% vs 0,9\% in the MCHT group; p<0,05), and was significantly worse on those who received DFO therapy. Based on our data, we suggest that TBI is detrimental for pancreatic functions, and speculate that DFO may contribute to the rapid pancreatic IO observed in these patients.

}, issn = {1949-2553}, doi = {10.18632/oncotarget.24646}, author = {Maximova, Natalia and Gregori, Massimo and Simeone, Roberto and Sonzogni, Aurelio and Zanon, Davide and Boz, Giulia and D{\textquoteright}Antiga, Lorenzo} } @article {10537, title = {Comparison of Efficacy and Safety of Caspofungin Versus Micafungin in Pediatric Allogeneic Stem Cell Transplant Recipients: A Retrospective Analysis.}, journal = {Adv Ther}, volume = {34}, year = {2017}, month = {2017 05}, pages = {1184-1199}, abstract = {

INTRODUCTION: The high morbidity and mortality associated with invasive fungal infections (IFIs) provide the rationale for antifungal prophylaxis in immuno-compromised pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). Caspofungin and micafungin are antifungal agents of interest for prophylaxis of IFIs because of their potency against Candida and minimal toxicity or interactions with other drugs. Few studies have demonstrated the safety and efficacy of such echinocandins as prophylaxis for IFIs in patients undergoing HSCT.

METHODS: This retrospective cohort study compared caspofungin and micafungin for prevention of IFIs in 93 pediatric patients undergoing HSCT for oncological or non-oncological disease. The observation began with the first dose of antifungal agent and ended 3~months after transplantation.

RESULTS: Patients in the micafungin group had a higher overall treatment success rate of 87.2 versus 84.8\% in the caspofungin group, but the difference was not significant. There were no statistically significant differences in the incidence or type of proven/probable IFIs between the 2 groups. The low incidence of death did not differ statistically between the groups. Patients in the caspofungin group presented more frequently with fever, during and after neutropenia. In both groups, we observed an expected worsening of blood chemistry parameters. There were no adverse events definitely attributable to the two antifungal agents.

CONCLUSION: These results demonstrate good efficacy and tolerability for caspofungin and micafungin. However, better results with respect to the incidence and resolution of fever in the micafungin group may suggest its use in preference to that of caspofungin.

}, keywords = {Adolescent, Antifungal Agents, Caspofungin, Child, Child, Preschool, Cohort Studies, Echinocandins, Female, Hematopoietic Stem Cell Transplantation, Humans, Infant, Infant, Newborn, Lipopeptides, Male, Micafungin, Mycoses, Neutropenia, Retrospective Studies}, issn = {1865-8652}, doi = {10.1007/s12325-017-0534-7}, author = {Maximova, Natalia and Schillani, Giulia and Simeone, Roberto and Maestro, Alessandra and Zanon, Davide} } @article {10536, title = {First-time success with needle procedures was higher with a warm lidocaine and tetracaine patch than an eutectic mixture of lidocaine and prilocaine cream.}, journal = {Acta Paediatr}, volume = {106}, year = {2017}, month = {2017 May}, pages = {773-778}, abstract = {

AIM: More than 50\% of children report apian during venepuncture or intravenous cannulation and using local anaesthetics before needle procedures can lead to different success rates. This study examined how many needle procedures were successful at the first attempt when children received either a warm lidocaine and tetracaine patch or an eutectic mixture of lidocaine and prilocaine (EMLA) cream.

METHODS: We conducted this multicentre randomised controlled trial at three tertiary-level children{\textquoteright}s hospitals in Italy in 2015. Children aged three to 10 years were enrolled in an emergency department, paediatric day hospital and paediatric ward and randomly allocated to receive a warm lidocaine and tetracaine patch or EMLA cream. The primary outcome was the success rate at the first attempt.

RESULTS: The analysis included 172 children who received a warm lidocaine and tetracaine patch and 167 who received an EMLA cream. The needle procedure was successful at the first attempt in 158 children (92.4\%) who received the warm patch and in 142 children (85.0\%) who received the cream (p = 0.03). The pain scores were similar in both groups.

CONCLUSION: This study showed that the first-time needle procedure success was 7.4\% higher in children receiving a warm lidocaine and tetracaine patch than EMLA cream.

}, keywords = {Anesthetics, Local, Catheterization, Peripheral, Child, Child, Preschool, Female, Hot Temperature, Humans, Lidocaine, Lidocaine, Prilocaine Drug Combination, Male, Pain, Phlebotomy, Prilocaine, Tetracaine}, issn = {1651-2227}, doi = {10.1111/apa.13764}, author = {Cozzi, Giorgio and Borrometi, Fabio and Benini, Franca and Neri, Elena and Rusalen, Francesca and Celentano, Loredana and Zanon, Davide and Schreiber, Silvana and Ronfani, Luca and Barbi, Egidio} } @article {8510, title = {Hepatic Gadolinium Deposition and Reversibility after Contrast Agent-enhanced MR Imaging of Pediatric Hematopoietic Stem Cell Transplant Recipients.}, journal = {Radiology}, year = {2016}, month = {2016 Jun 8}, pages = {152846}, abstract = {

Purpose To determine if hepatic gadolinium deposition occurs in pediatric patients with iron overload but normal renal and hepatic function who undergo gadolinium-based contrast agent (GBCA)-enhanced magnetic resonance (MR) imaging. Materials and Methods Design and execution of this study was approved by the Ethical Committee of Institute for Research in Maternal and Child Health Burlo Garofolo of Trieste (reference no. 1105/2015). Because of the retrospective nature of the study, the requirement to obtain informed consent was waived. Twenty-one recipients of allogeneic hematopoietic stem cell transplants who underwent GBCA-enhanced MR imaging for suspected infection or relapse followed by liver biopsy comprised the study group. The number of GBCA-enhanced MR examinations and cumulative gadolinium dose for each patient was analyzed by comparing liver histologic analysis and iron and gadolinium liver concentration (GLC). Eight patients had siderosis and underwent chelation therapy. The study group was compared with four control patients who were never exposed to GBCA. Statistical analysis was performed with Spearman rank coefficient for correlation. Results All 21 patients had positive correlations between GLC and total GBCA dose (r = 0.4486; P < .05) and between GLC and liver iron concentration (r = 0.56; P < .05). Patients who underwent deferoxamine therapy had a significant reduction of GLC (from 0.64 μg/g {\textpm} 0.29 to 0.20 μg/g {\textpm} 0.17 [standard deviation]; P < .05). Conclusion In the presence of siderosis, a transmetallation mechanism may be set off between ferric ion and gadoterate meglumine. Deferoxamine appears capable of binding to gadolinium ion. Further studies of the safety of GBCAs in severe siderosis are needed. Chelation should be considered in patients with iron overload and a history of GBCA exposure. ({\textcopyright}) RSNA, 2016.

}, issn = {1527-1315}, doi = {10.1148/radiol.2016152846}, author = {Maximova, Natalia and Gregori, Massimo and Zennaro, Floriana and Sonzogni, Aurelio and Simeone, Roberto and Zanon, Davide} } @article {7706, title = {Metal accumulation in the renal cortex of a pediatric patient with sickle cell disease: a case report and review of the literature.}, journal = {J Pediatr Hematol Oncol}, volume = {37}, year = {2015}, month = {2015 May}, pages = {311-4}, abstract = {

BACKGROUND: Sickle cell disease (SCD) is a well-known multisystem illness characterized by vascular injury due to vasoocclusion and hemolysis, as well as infectious complications and iron overload, all of which contribute to high morbidity and mortality rates among children. In these patients, some authors have previously described iron cortical deposition in the kidney. We here report the first case in the literature of a girl affected by SCD showing an anomalous metal and rare element retention in the renal cortex.

CASE PRESENTATION: A 10-year-old white girl affected by SCD underwent a routine magnetic resonance imaging investigation that evidenced a reduced signal intensity in the renal cortex, compatible with hemosiderin precipitation. Histologic and elemental analyses of the hepatic and the renal biotic samples, performed with inductively coupled plasma mass spectrometry, revealed that concomitant with the high iron deposition, toxic and potentially carcinogenic elements such as nickel, magnesium, rubidium, and gadolinuim were anomalously retained particularly in the kidney.

CONCLUSIONS: The finding of rare and toxic elements in the kidney of SCD patients might be linked to the development of specific neoplastic transformations already described in this patient cohort. To be confirmed, our speculations need to be demonstrated in large sampling of patients.

}, keywords = {Anemia, Sickle Cell, Child, Female, Humans, Kidney Cortex, Metals, Spectrophotometry, Atomic}, issn = {1536-3678}, doi = {10.1097/MPH.0000000000000322}, author = {Maximova, Natalia and Zanon, Davide and Pascolo, Lorella and Zennaro, Floriana and Gregori, Massimo and Grosso, Daniele and Sonzogni, Aurelio} } @article {1887, title = {Sedation with intranasal midazolam of Angolan children undergoing invasive procedures.}, journal = {Acta Paediatr}, volume = {101}, year = {2012}, month = {2012 Jul}, pages = {e296-8}, abstract = {

AIM: Ambulatory surgery is a daily requirement in poor countries, and limited means and insufficient trained staff lead to the lack of attention to the patient{\textquoteright}s pain. Midazolam is a rapid-onset, short-acting benzodiazepine which is used safely to reduce pain in children. We evaluated the practicability of intranasal midazolam sedation in a suburban hospital in Luanda (Angola), during the surgical procedures.

METHODS: Intranasal midazolam solution was administered at a dose of 0.5 mg/kg. Using the Ramsay{\textquoteright}s reactivity score, we gave a score to four different types of children{\textquoteright}s behaviour: moaning, shouting, crying and struggling, and the surgeon evaluated the ease of completing the surgical procedure using scores from 0 (very easy) to 3 (managing with difficulty).

RESULTS: Eighty children (median age, 3 years) were recruited, and 140 surgical procedures were performed. Fifty-two children were treated with midazolam during 85 procedures, and 28 children were not treated during 55 procedures. We found a significant difference between the two groups on the shouting, crying and struggling parameters (p < 0.001). The mean score of the ease of completing the procedures was significantly different among the two groups (p < 0.0001).

CONCLUSION: These results provide a model of procedural sedation in ambulatory surgical procedures in poor countries, thus abolishing pain and making the surgeon{\textquoteright}s job easier.

}, keywords = {Administration, Intranasal, Adolescent, Ambulatory Surgical Procedures, Angola, Child, Child Behavior, Child, Preschool, Conscious Sedation, Crying, Female, Humans, Hypnotics and Sedatives, Infant, Male, Midazolam, Prospective Studies}, issn = {1651-2227}, doi = {10.1111/j.1651-2227.2012.02691.x}, author = {Kawanda, Lumana and Capobianco, Ivan and Starc, Meta and Felipe, Daniel and Zanon, Davide and Barbi, Egidio and Munkela, Nadine and Rodrigues, Ver{\'o}nica and Malundo, L{\'u}is and Not, Tarcisio} } @article {1834, title = {Glutamine-enriched nutrition does not reduce mucosal morbidity or complications after stem-cell transplantation for childhood malignancies: a prospective randomized study.}, journal = {Transplantation}, volume = {91}, year = {2011}, month = {2011 Jun 27}, pages = {1321-5}, abstract = {

BACKGROUND: Intravenous glutamine-enriched solution seems to be effective in posttransplant period in decreasing the severity and duration of mucositis. The aim of this randomized study was to determine the benefit of glutamine supplementation both on mucosal morbidity and in posttransplant associated complications.

METHODS: Children undergoing allogeneic hematopoietic stem-cell transplantation (HSCT) for malignant hematological diseases were randomly assigned to standard total parenteral nutrition (S-TPN) or glutamine-enriched (GE)-TPN solution consisting of 0.4 g/kg/day of l-alanine-glutamine dipeptide. This treatment started on the day of HSCT and ended when the patients could orally cover more than 50\% of their daily energy requirements. The severity and the rate of post-HSCT mucositis were based on World Health Organization criteria. All the analyses were conducted on intention-to-treat principle.

RESULTS: One hundred twenty consecutive patients (83 men; median age, 8.1 years) were enrolled. The mean duration of treatment was 23.5 and 23 days in the two treatment arms. The mean calorie intake was 1538 kcal/d in the S-TPN group and 1512 kcal/d in GE-TPN group. All patients were well nourished before and after HSCT. Mucositis occurred in 91.4\% and 91.7\% of patients in S-TPN and GE-TPN arm, respectively (P=0.98). Odds ratio adjusted by type of HSCT was 0.98 (95\% confidence interval, 0.26-2.63). Type and duration of analgesic treatment, clinical outcome (engraftment, graft versus host disease, early morbidity, and mortality, relapse rate up to 180 days post-HSCT) were not significantly different in the two treatment arms.

CONCLUSION: GE-TPN solution does not affect mucositis and outcome in well-nourished HSCT allogeneic patients.

}, keywords = {Adolescent, Analgesia, Child, Child, Preschool, Double-Blind Method, Female, Glutamine, Hematopoietic Stem Cell Transplantation, Humans, Infant, Male, Mucositis, Mucous Membrane, Neoplasms, Odds Ratio, Parenteral Nutrition, Prospective Studies, Recurrence, Stem Cells, Treatment Outcome}, issn = {1534-6080}, doi = {10.1097/TP.0b013e31821ab959}, author = {Uderzo, Cornelio and Rebora, Paola and Marrocco, Emanuela and Varotto, Stefania and Cichello, Francesca and Bonetti, Maurizio and Maximova, Natalia and Zanon, Davide and Fagioli, Franca and Nesi, Francesca and Masetti, Riccardo and Masetti, Roberto and Rovelli, Attilio and Rondelli, Roberto and Valsecchi, Maria Grazia and Cesaro, Simone} } @article {1621, title = {A web-based system for total parenteral nutrition prescription in a pediatric hospital - biomed 2010.}, journal = {Biomed Sci Instrum}, volume = {46}, year = {2010}, month = {2010}, pages = {351-6}, abstract = {

otal Parenteral Nutrition (TPN) is defined as feeding a patient by infusing nutrients intravenously, bypassing the usual process of eating and digestion. There are two kinds of TPN: short-term TPN may be used when a patient{\textquoteright}s digestive system is temporarily nonfunctional because of an interruption in its continuity; long-term TPN is used to treat patients with an impairment or a lack in nutrient absorption. TPN has extended the life of children born with nonexistent or severely deformed digestive organs and is a vital support for these patients. In Burlos Pediatric Department, pediatricians fill in a pharmacy request form in which nutritional needs are included for each patient. Subsequently, clinical pharmacists evaluate the patients individual data and decide which TPN formula to prepare. To enhance the TPN prescription process, an intranet web-based system has been developed to replicate the original paper-based forms. The software, developed in PHP and based on open source tools and services, has been constructed according to pharmacists requirements. These professionals, together with the Hospital Information System technicians, thanks to the availability of affordable instruments, perceive the advantages that such a system would have in improving clinical practice and quality of care. The system was devised with the goal to avoid common reading errors, to improve the correct text comprehension, to ensure prescription preparation, administration and tracking. According to a process of total quality control, the system reduces clinical risks regarding issues such as the correct and rapid availability of medical prescriptions and the incorrect identification of the patients. In comparison with paper-based TPN prescriptions, electronic-based forms have reduced the incidence of errors, the possible lack of patient data and reading misunderstandings. Regarding future improvements, IT technicians are defining the procedures to implement digital signature and medical aspects of the electronic TPN medical prescriptions.

}, issn = {0067-8856}, author = {Bava, Michele and Bradashia, Fulvio and Rovere, Francesca and Maestro, Alessandra and Vecchi Brumatti, Liz and Accardo, Agostino and Paparazzo, Rossella and Zanon, Davide} }