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Introduction: We performed this study aiming to evaluate changes in epidemiology, clinical presentation and outcomes of children hospitalized for viral lower respiratory tract infections (LRTI).Methods: We performed a retrospective study of children younger than 18 years of age hospitalized for LRTIs with a positive respiratory viral testing from 2018 to 2022. We compared need of pediatric intensive care unit (PICU), invasive ventilation, and other respiratory support, viral etiologies, clinical presentations, imaging, and laboratory results in the precovid (2018-2019) and covid (2020-2022) period.Results: A total of 523 were included in the analysis. In the pandemic period, the detection of influenza was 95% less likely to occur (odds ratio [OR]: 0.05; 95% confidence interval [95% CI]: 0.02-0.12; p < .001), likewise the detection of adenovirus was 77% less likely to occur (OR: 0.23; 95% CI: 0.10-0.51; p < .001). In the pandemic period, the number of codetections increased from 15.52% in 2018 to 57.25% in 2022, resulting in a significantly increasing trend (p < .001). The odds of transfer to PICU was more than five times greater during the pandemic period (OR: 5.31; 95% CI: 1.78-15.86; p = .003).Conclusions: We found that the pattern of LRTI in children during COVID-19 pandemic significantly changed in terms of etiologies and increased severity.

Background: The CHOP-INTEND is an established outcome measure used to assess motor function in young and weak SMA patients previously validated in type I infants older than 3 months. Objective: The aim of our study was to assess the maturation of the CHOP-INTEND scores in a group of healthy infants, establishing which items of the scale can be reliably used in individuals younger than 3 months. Methods: This is a prospective observational study. The whole cohort was divided into 5 age groups. Each of the 16 CHOP-INTEND items was analyzed looking at the frequency distribution of the scores in each age subgroup. An item was considered developmentally appropriate when > 85% of the infants achieved a full score. Results: our study includes 61 assessments collected < 2 weeks, 25 at 2-4 weeks, 20 at 5-8 weeks, 25 at 9-12 weeks and 20 at 13-17 weeks. Eight of the 16 items were developmentally appropriate already in the first week and another by the end of the first month. The remaining 7 items had more variable responses in the first three months and full scores were consistently achieved only after the third month. Conclusions: Our findings suggest that the CHOP-INTEND can be used before the age of 3 months, but the results should be interpreted with caution, considering which items are developmentally appropriate at the time of testing. This will also help to establish whether the changes observed following early treatments are a sign of efficacy or at least partly reflect maturational aspects.

Introduction: There is marked heterogeneity in clinicians' choice of antibiotic duration for pediatric urinary tract infections (UTIs). Most patients with bacterial UTIs still receive between 7 and 10 days of antibiotics. Prolonged antibiotic exposure drives the emergence of resistance and increases the occurrence of adverse effects. There is increasing evidence that shorter antibiotic regimens may be equally effective compared with longer ones. However, studies evaluating shorter therapies in children hospitalized with urinary tract infections have not yet been performed. Methods: We performed a retrospective study comparing children hospitalized with UTIs treated with a short antibiotic (<7 days) or standard antibiotic treatment. The primary aim of our study was to assess the efficacy of a shorter antibiotic therapy for children with UTIs, compared with an historical group of children treated with a standard 7-14 days course. Results: 112 patients, 46 of which were females (41.1%) with a median age 6 months were enrolled. A total of 33 patients (29.5%) underwent a short therapy. All patients were successfully discharged from the acute episode, independently from antibiotic duration. Short therapy was associated with a lower risk of urinary tract relapse (22 relapses (95.6%) in the standard group, 1 (4.4%) in the short group; OR 0.081; 95%CI 0.01-0.63). Conclusions: Short antibiotic therapy was equivalent to standard duration therapy for the cure of UTIs in hospitalized children and was also associated with a lower rate of recurrences. This study provides the basis for a larger prospective randomized study to address the role of short antibiotic therapies in children with UTIs requiring hospitalization

Purpose: The COVID-19 pandemic has affected the mental and physical health of the world population. This study aims to investigate incidence of sleep-related difficulties and post-traumatic stress disorder in the school-aged children after 1 year of the pandemic. Methods: A sample of Italian children (6-12 years) was queried about their sleep behaviors after 1 year of the pandemic, answering the Children's Sleep Habits Questionnaire (CSHQ). We also evaluated trauma symptoms with the Children's Impact of Event Scale (CRIES-8). Results: Among 205 participants, 184 (89.8%) presented sleep-related difficulties. Out of all, 99 (48.3%) had a high risk to develop post-traumatic stress disorder. Ninety-five (51.6%) children with sleep-related difficulties also presented an abnormal CRIES-8 total score. A correlation was found between the CSHQ total score and the CRIES-8 total score (r = 0.354, P < .01). Conclusions: The sleep-related difficulties occurring during COVID-19 outbreak may compound to increase the risk to develop post-traumatic stress disorder among Italian children.

Aim Myopericarditis after COVID-19 vaccination were the most serious adverse events reported in children over 5 years of age. We want to summarise these cases, describing their incidence, clinical features, diagnostic pathways, therapeutic strategies and outcome. Methods A systematic review of the literature was conducted until 20 March 2022 by bibliographic electronic databases. We included all reports of post-vaccination myopericarditis in children aged between 5 and 18 years. Results All reported cases had elevated serum Troponin levels, associated with electrocardiogram changes, but often with normal echocardiogram. Cardiac magnetic resonance images always showed typical alterations. The pathogenetic mechanism is still unknown. Myocarditis following post-COVID vaccination is more frequent in boys with an average age of about 15 years. Treatment involves the usage of non-steroidal anti-inflammatory drugs, and the average hospitalisation is about 3 days. The long-term consequences are not yet known, so these patients should be studied in a cardiological follow-up and abstention from physical activity should be recommended. Conclusion The benefits of COVID-19 vaccination in children and adolescents appear to outweigh the risk of developing post-vaccination myopericarditis. We can also speculate a possible approval of vaccination in children under 5 years for the coming winter.

Study Objectives: The main aim was to evaluate the prevalence of sleep-disordered breathing (SDB) in patients with Chiari II malformation (CM-II). The secondary objectives were to evaluate the association between SDB, morphological abnormalities, and neurological symptoms and to review the literature on patients with SDB and CM-II.Methods: The study has a cross-sectional, case-control design. Patients with CM-II (patients) were compared to control patients referred for clinical polysomnography in the Sleep Medicine Unit, matched for age and sex. All patients underwent brain and spinal cord magnetic resonance imaging, and polysomnography was conducted for all participants. A review of the literature about SDB in patients with CM-II was performed.Results: Forty patients were included (20 patients vs 20 control patients). SDB was identified in 45% of patients, a significantly higher prevalence compared to control patients. Three patients presented with purely obstructive SDB, 3 patients with purely central SDB, and 3 patients with both obstructive and central SDB. Compared with control patients, patients with CM-II showed a higher oxygen desaturation index (median: CM-II, 3.7; interquartile range, 1.6-19.5; control patients: 1.1; interquartile range, 0.3-3.2) and obstructive apnea-hypopnea index (median: CM-II, 1.5; interquartile range, 0.5-5.1; control patients, 0.1; interquartile range, 0.0-0.7). A logistic regression showed that the risk of developing SDB in patients affected by CM-II was 14.7 times higher than in the control population.Conclusions: Our study and literature review showed a high prevalence of SDB in patients with CM-II. These patients are often asymptomatic at diagnosis, suggesting that PSG should be routinely provided in this population.

Background:Infectious encephalitis represents a rare but potentially severe clinical condition. However, limited international data are available in pediatric age.Methods:We conducted a retrospective study to review (a) the clinical presentation; (b) laboratory, radiology, and neurophysiology findings; (c) the correlations between these exams and outcome; and (d) the therapy performed.Results:Fifty-six patients were enrolled [22 female (39.6%), mean age 4.7 years, IQR 0.7-8.7 years], 19.6% presented neurologic sequelae. HSV was the single most frequently isolated pathogen (19.6%), although in most cases, the etiology remained undefined. 41.1% children presented prodromal before the development of neurologic signs. Fever was the most frequent constitutional symptom (83.9% of cases). Cerebrospinal fluid was normal in 48.5% of cases and electroencephalograpy in 24.5% cases. Brain computed tomography scans was normal in 33 (91.7%) cases, while cerebral magnetic resonance imaging (MRI) showed pathologic findings in 62.5% of cases. MRI was the only parameter associated with neurologic sequalae [P = 0.01; OR, 8.1 (95% CI: 1.52-42.84)].Conclusions:Pediatric encephalitis is a heterogeneous entity with nonspecific clinical and laboratory findings, with undefined etiologies in most times. MRI can play a primary role, both on a diagnostic and prognostic point-of-view, and its role should be implemented and made more accessible. Further studies are needed to define the exact role and timing of steroids.

Kawasaki disease (KD) is a childhood vasculitis of unknown etiology. The present study describes a case of KD shock syndrome that occurred in an infant (age, 16 months) following 7 days of high fever and persistent rash characterized by target-like and purpuric skin lesions. The child developed neurological manifestations such as altered consciousness and irritability. Consequently, brain magnetic resonance imaging (MRI) was performed, revealing an inflammatory involvement of the anterior perforated substance and the hypothalamus. Cerebral involvement on brain MRI is rarely described in KD but when reported is characterized mostly by cerebral vasculitis. We illustrate for the first time in KD an inflammation in the brain not related to vasculitis, reporting peculiar neuroradiological findings. This last aspect has fascinated us in light of recent evidence about the immunological spectrum of Multisystem Inflammatory Syndrome in Children (MIS-C) and Kawasaki-like syndrome in the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) outbreak.

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Acute pain is one of the most common symptoms in children admitted to the Pediatric Emergency Department (PED) and its management represents a real clinical challenge for pediatricians. Different painful procedures can be very stressful for young children and their perception of pain can be enhanced by emotional factors, such as anxiety, distress, or anger. Adequate procedural sedation reduces anxiety and emotional trauma for the patient, but it reduces also stress for operators and the time for procedures. We have reviewed the literature on this topic and the drugs covered in these papers were: midazolam, fentanyl, ketamine, and dexmedetomidine. There are several routes of administering for these drugs to provide analgesia and anxiolysis to children: oral, parenteral, or intranasal (IN). Intravenous (IV) sedation, since it involves the use of needles, can be stressful; instead, IN route is a non-invasive procedure and generally well tolerated by children and it has become increasingly widespread. Some medications can be administered by a mucosal atomizer device (MAD) or by drops. The benefits of the atomized release include less drug loss in the oropharynx, higher cerebrospinal fluid levels, better patient acceptability, and better sedative effects. IN midazolam has a sedative, anxiolytic and amnesic effect, but without analgesic properties. Fentanyl and ketamine are mainly used for pain control. Dexmedetomidine has anxiolytic and analgesic properties. In conclusion, IN analgo-sedation is a simple, rapid and painless option to treat pain and anxiety in the PED requiring brief training on the administration process and experience in sedation.

No abstract available

Kawasaki disease (KD) is an acute, febrile illness of unknown etiology that mainly affects children under 5 years of age. intravenous immunoglobulin (IVIG), the standard treatment, has reduced coronary involvement to <5%. Patients who do not improve after an initial IVIG have a higher risk of developing coronary arteries aneurysms, and its optimal treatment remains controversial. We present a case of IVIG, steroids, and infliximab-resistant KD in a 9-month-old child, which developed giant aneurysms and was successfully treated with anakinra, a recombinant antagonist of the IL-1 receptor. In our case, the introduction of IL-1 receptor antagonist therapy seems to have blocked the disease from both a clinical and a laboratory point of view. We also noted a very rapid regression of coronary aneurysms passed from giant aneurysms to small ones, or, as in the case of the anterior descending artery, the complete disappearance of the aneurysm formation. We think that our case adds more evidences to the potential role of IL-1RA as therapy in some selected cases of refractory KD, in particular with severe involvement of coronary arteries, although new efficacy trials are needed to better understand the role of Anakinra in these patients.

Hemophilia A is an X-linked bleeding disorder caused by a deficiency of factor VIII. Depending on the factor VIII activity in patient's plasma, we can have three different forms of hemophilia A: mild (5-40 IU/dl), moderate (1-5 IU/dl) and severe (<1 IU/dl). The most common symptoms include recurrent bleeding episodes of soft tissues and joints. The treatment is based on the prophylactic use of clotting factor concentrates to prevent bleeding episodes. We describe three cases of patients with initially diagnosis of hemophilia A that show different clinical severity, undergoing prophylactic therapies with low benefit. In these patients, the dosage of von Willebrand antigen revealed either low level or absence of this factor, which in one case was caused by the occurrence of a type III form of von Willebrand disease

Lung ultrasound (LUS) is nowadays a fast-growing field of study since the technique has been widely acknowledged as a cost-effective, radiation free, and ready available alternative to standard X-ray imaging. However, despite extensive acoustic characterization studies and documented medical evidences, a lot is still unknown about how ultrasounds interact with lung tissue. One of the most discussed lung artifacts are the B-lines [in all ages] and the subpleural consolidations (in young infants). Recently, LUS has been claimed to be able to detect pneumonia in infants with bronchiolitis, although this can be an overestimation due to the peculiar physiology of small peripheral airways of the pediatric lung (particularly in neonate/infants). Distinguishing consolidations from atelectasis in young infants with bronchiolitis can be challenging and those criteria well defined for adults and older children (size and bronchogram) cannot easily translated in this specific subset. Therefore, if decades of studies clearly defined the low risk of SBI in bronchiolitis, we need to be careful before stating that LUS may confirm pneumonia in such a high number of cases and, importantly, new and promising techniques such as LUS should give us new insights bringing us to improvements and not back to overuse of antibiotics. More studies are surely need on this topic.

Hereditary spherocytosis is the most common inherited hemolytic anemia characterized by the presence of spherical-shaped erythrocytes on peripheral blood smear. The clinical manifestations of HS are highly variable, from severe forms to asymptomatic forms. HS is caused by defects in red blood cell membrane proteins, encoded by the ANK1, EPB42, SLC4A1, SPTA1 and SPTB genes. Mutation of the ANK 1 gene is the most common and inheritance is autosomal dominant in 75% of cases. In our case, heterozygous an ANK1 c.4123C > T mutation was identified in a 4-year-old girl, using targeted next-generation sequencing and Sanger sequencing.

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A child with linear IgA bullous dermatosis, appeared after after administration of aspirin, is herein reported.

Paediatric optic pathway gliomas are low-grade brain tumours characterized by slow progression and invalidating visual loss. Presently there is no strategy to prevent visual loss in this kind of tumour. This study evaluated the effects of nerve growth factor administration in protecting visual function in patients with optic pathway glioma-related visual impairment. A prospective randomized double-blind phase II clinical trial was conducted in 18 optic pathway glioma patients, aged from 2 to 23 years, with stable disease and severe visual loss. Ten patients were randomly assigned to receive a single 10-day course of 0.5 mg murine nerve growth factor as eye drops, while eight patients received placebo. All patients were evaluated before and after treatment, testing visual acuity, visual field, visual-evoked potentials, optic coherence tomography, electroretinographic photopic negative response, and magnetic resonance imaging. Post-treatment evaluations were repeated at 15, 30, 90, and 180 days Brain magnetic resonance imaging was performed at baseline and at 180 days. Treatment with nerve growth factor led to statistically significant improvements in objective electrophysiological parameters (electroretinographic photopic negative response amplitude at 180 days and visual-evoked potentials at 30 days), which were not observed in placebo-treated patients. Furthermore, in patients in whom visual fields could still be measured, visual field worsening was only observed in placebo-treated cases, while three of four nerve growth factor-treated subjects showed significant visual field enlargement. This corresponded to improved visually guided behaviour, as reported by the patients and/or the caregivers. There was no evidence of side effects related to nerve growth factor treatment. Nerve growth factor eye drop administration appears a safe, easy and effective strategy for the treatment of visual loss associated with optic pathway gliomas.

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A case of severe myopericarditis is presented and response to high-dose intravenous immunoglobulin is highlighted.

This case report highlights how extensive irregular Mongolian blue spots may represent a clue for the diagnosis of GM1 gangliosidosis type 1.

ongenital thrombotic thrombocytopenic purpura (TTP) is a rare form of thrombotic microangiopathy, inherited with autosomal recessive mode as a dysfunction or severe deficiency of ADAMTS-13 (A Disintegrin And Metalloprotease with ThromboSpondin 1 repeats Nr. 13), caused by mutations in the ADAMTS-13 gene. About 100 mutations of the ADAMTS-13 gene were identified so far, although only a few characterised by in vitro expression studies. A new Asp to Gly homozygous mutation at position 173 of ADAMTS-13 sequence was identified in a family of Romanian origin, with some members affected by clinical signs of TTP. In two male sons, this mutation caused a severe (< 3%) deficiency of ADAMTS-13 activity and antigen level, associated with periodic thrombocytopenia, haemolytic anaemia and mild mental confusion. Both parents, who are cousins, showed the same mutation in heterozygous form. Expression studies of the mutant ADAMTS-13, performed in HEK293 cells, showed a severe decrease of the enzyme's activity and secretion, although the protease was detected inside the cells. Molecular dynamics found that in the D173G mutant the interface area between the metalloprotease domain and the disintegrin-like domain significantly decreases during the simulations, while the proline-rich 20 residues linker region (LR, 285-304) between them undergoes extensive conformational changes. Inter-domain contacts are also significantly less conserved in the mutant compared to the wild-type. Both a decrease of the inter-domain contacts along with a substantial conformational rearrangement of LR interfere with the proper maturation and folding of the mutant ADAMTS-13, thus impairing its secretion.

Background: The purpose of this study was to assess the efficacy and toxicity of radiotherapy (RT) with concurrent temozolomide (TMZ) chemotherapy followed by adjuvant TMZ in children with diffuse intrinsic pontine glioma (DIPG). Methods: Patients younger than 18 years with newly diagnosed DIPG were enrolled. Children were treated with focal RT along with concurrent daily TMZ. Four weeks after completing the initial RT-TMZ schedule, adjuvant TMZ was given every 28 days up to 12 cycles or progression disease. Results: Fifteen children with a median age of 9 years were enrolled. Fourteenth out of the 15 patients completed the chemoradiotherapy. The toxicity associated with TMZ was primarily haematopoietic. At a median follow-up of 15 months 13 children had died and 2 children were alive with progressive disease. No patient experienced complete response (CR). The median time to progression was 7·15 months. Conclusion: Chemoradiotherapy with TMZ followed by adjuvant TMZ did not improve the poor prognosis associated with DIPG in children.

The treatment of children with malignant glioma remains challenging. The aim of this multicenter phase I study is to establish the recommended dose (RD) of the combination therapy with temozolomide (TMZ) and oral etoposide (VP-16) in children with relapsed or refractory malignant glioma and brainstem glioma at diagnosis. A phase I trial was conducted to establish the maximum tolerated dose (MTD) of TMZ and oral VP-16. This orally administered combination was investigated by a classical 3 + 3 design. Cohorts of patients were enrolled at 4 different levels: (1) TMZ 120 mg/m(2) on days 1-5 and VP-16 50 mg/m(2) on days 1-8; (2) TMZ 150 mg/m(2) on days 1-5 and VP-16 50 mg/m(2) on days 1-8; (3) TMZ 150 mg/m(2) on days 1-5 and VP-16 50 mg/m(2) on days 1-10; (4) TMZ 150 mg/m(2) on days 1-5 and VP-16 50 mg/m(2) on days 1-12. Therapy was administered in 28-day courses. A total of 118 courses were administered to 18 patients with a median age of 11.2 years. At dose level 1, none displayed toxicity. Of the 6 patients at dose level 2, 1 patient had dose limiting toxicity (DLT). None of the 3 patients at dose level 3 had DLT. At dose level 4, grade III/IV thrombocytopenia and neutropenia were observed in 2 out of the 6 patients enrolled. Therefore, the MTD was established at dose level 3. The RD for phase II trial in children with malignant glial is TMZ 150 mg/m(2) for 5 days and VP-16 50 mg/m(2) for 10 days every 28 days.

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BACKGROUND: To date, no specific therapy is available for optic glioma (OG)-induced visual loss. OBJECTIVE: To evaluate the effects on visual function of murine nerve growth factor (NGF) eye drop administration in children with severe visual impairment due to low-grade OGs. METHODS: Five patients with OGs and advanced optic nerve atrophy were assessed before and after a single 10-day course of 1 mg murine NGF topical administration by clinical evaluation, visual evoked potentials (VEPs), and brain magnetic resonance imaging (MRI). VEPs, the main functional outcome measure, were recorded at baseline and 1, 30, 45, 90, and 180 days posttreatment. MRI examinations were performed at baseline and at 180 days after NGF treatment. Six untreated control patients with OGs also underwent serial VEPs, clinical testing, and MRI assessments. RESULTS: After NGF treatment, median VEPs amplitude showed a progressive increase from the baseline values (P < .01). VEPs reached a maximum amplitude at 90 days (170% increase) and declined at 180 days, still remaining above the baseline level. Perception of spontaneous visual phosphenes was noted in all patients after NGF administration. MRI showed stable tumor size. In controls, clinical findings and VEPs did not show any significant change over the observation period. CONCLUSIONS: The findings from the study show that NGF administration may be an effective and safe adjunct therapy in children with optic atrophy due to OGs. The beneficial effect on optic nerve function suggests a visual rescuing mechanism exerted by murine NGF on the residual viable optic pathways.

Temozolomide (TMZ) is an oral alkylating agent with proven antitumoral activity in preclinical and clinical studies in adults with high-grade glioma (HGG). However, only limited efficacy has been reported in children with HGG using the 5-day schedule. This study investigated the safety of administering TMZ to children and adolescents with brain tumors over an extended period. Extended schedules have been proven to overcome chemoresistance without any major toxicity. The toxicity of TMZ, administered at 70 mg/m(2)/day orally for 21 consecutive days every 28 days, was assessed in children with brain tumors. A total of 156 courses of TMZ were given to 17 patients (median age 12.5 years, range 1-17 years), who were recruited into the study. Eleven patients had progressive or relapsing disease, and six patients were newly diagnosed. In this cohort no cases of toxic death or nonhematological toxicity were reported. In comparison with the 5-day schedule, thrombocytopenia and neutropenia were noted to be less frequent. Grades 3 and 4 lymphopenia occurred in 10.8 and 22.4% of courses, respectively; among the lymphopenic patients there was one case of disseminated zoster (meningoencephalitis and cutaneous involvement), one case of rotavirus gastroenteritis, and two cases of herpetic stomatitis reported. The objective response rate was 11.8%. Overall, 82.3% of patients showed stable disease. The prolonged TMZ schedule appeared to be well tolerated, with few cases of neutropenia or thrombocytopenia recorded. Nevertheless, prolonged exposure to TMZ was associated with lymphopenia and may lead to a higher rate of viral infections.

BACKGROUND: The prognosis of recurrent or progressive medulloblastoma (MB) is still poor. This study was designed to investigate the potential therapeutic benefit of combination therapy with temozolomide (TMZ) and oral etoposide (VP-16) in children with progressive or relapsed MB. Given the oral administration of both drugs the regimen was administered outpatient. METHODS: A phase I trial was conducted to establish the maximum tolerated dose (MTD) of TMZ and oral VP-16. This orally administered combination was investigated by classical 3+3 design. Cohorts of patients were enrolled at four different levels: (1) TMZ 120 mg/m(2) on days 1-5 and VP-16 50 mg/m(2) on days 1-8; (2) TMZ 150 mg/m(2) on days 1-5 and VP-16 50 mg/m(2) on days 1-8; (3) TMZ 150 mg/m(2) on days 1-5 and VP-16 50 mg/m(2) on days 1-10; (4) TMZ 150 mg/m(2) on days 1-5 and VP-16 50 mg/m(2) on days 1-12. Therapy was administered in 28-d courses. A total of 66 courses were administered to 14 patients with a median age of 5.7 years. RESULTS: None of the 3 patients at dose levels 1 and 2 had dose-limiting toxicity (DLT). Of the 6 patients at dose level 3, 1 patient had DLT. At dose level 4, grade 4 thrombocytopaenia and neutropaenia were observed in the first 2 patients enrolled. Therefore, the MTD was established at dose level 3. CONCLUSION: The recommended phase II dose in children is TMZ 150 mg/m(2) on days 1-5 and VP-16 50 mg/m(2) on days 1-10 every 28 d. The combination was well tolerated and demonstrated antitumour activity.

Invasive procedures, such as the lumbar puncture, can cause anxiety and pain in children undergoing treatment for acute lymphoblastic leukaemia (ALL). We investigated the safety and efficacy of two different protocols for analgo-sedation in 20 children with ALL undergoing lumbar puncture. We have conducted a prospective, cross-over study. Protocol A was composed of an association between propofol and alfentanil. Protocol B consisted in the combination of propofol and ketamine. We also evaluated the levels of nerve growth factor, substance P and enkephalins in the cerebrospinal fluid of these patients. All patients showed a satisfactory sedation and analgesia. We found a statistically significant difference of vital parameters between protocol A and protocol B, while there were no significant differences between sedation scores and the other parameters evaluated. Patients in protocol A showed a higher incidence of major side effects, such as respiratory depression. Pain neuromediator levels did not show any statistical difference between the two groups. This study shows that both protocols are effective to obtain a good sedation and analgesia in children with ALL undergoing lumbar puncture, but the association between propofol and ketamine appears to be safer due to the lower incidence of side effects.

Yolk sac tumor is a rare germ cell neoplasm occurring mainly in the gonads. Extragonadal yolk sac tumor is a very rare malignancy; its main distribution is along the midline of the body at three principal sites: mediastinum, central nervous system and retroperitoneum. Most yolk sac tumors are diagnosed between seven months and three years of age. We report a case of primary yolk sac tumor in a 13-month-old child. The tumor was located in the pontocerebellar angle, an atypical location that may not have suggested a yolk sac tumor as first diagnosis. We want to highlight the importance of performing tumor marker measurements during the first year of life, also for tumors located away from the midline.

Familial adenomatous polyposis is an inherited disorder characterized by the development of hundreds of colorectal adenomas during adolescence, which in many cases will transform into colorectal cancer by the fourth decade of life, along with the development of various malignant tumors including hepatoblastoma. We report on a female patient with a de novo interstitial deletion of 5q21.3-q23.3, encompassing the APC gene, associated with adenomatous polyposis and early colorectal cancer, hepatoblastoma, epidermoid cysts, mental retardation, several mild dysmorphic signs and lower limb venous thrombosis.

The aim of this study was to evaluate longitudinally functional and neuro-radiologic findings in childhood optic gliomas (OG), by comparing flicker visual evoked potentials (F-VEPs) with brain magnetic resonance imaging (MRI) changes. Fourteen children (age range: 1-13 years) with OGs underwent serial F-VEP, MRI and neuro-ophthalmic examinations over a 38 month (median, range: 6-76) follow-up. F-VEPs were elicited by 8 Hz sine-wave flicker stimuli presented in a mini-Ganzfeld. Contrast-enhanced MRI examinations were performed. Results of both tests were blindly assessed by independent evaluators. F-VEPs were judged to be improved, stable or worsened if changes in the amplitude and/or phase angle of the response exceeded the limits of test-retest variability (+/-90th percentile) established for the same patients. MRI results were judged to show regression, stabilization or progression of OG based on its changes in size (+/-20%) or extension. Two to seven pairs of F-VEP/MRI examinations per patient (median: 4) were collected. Based on a total of 38 pairs of F-VEP/MRI examinations, both tests agreed in showing worsening (progression), stabilization and improvement (regression) in 5, 15 and 10 cases, respectively. In 3 cases, F-VEPs showed a worsening and MRI a stabilization, while in 5 cases F-VEPs showed an improvement and MRI a stabilization. Agreement between F-VEP and MRI changes was 78.9% (95% CI: +/- 37%, K statistics = 0.67, P < 0.001). The results indicate that longitudinal F-VEP changes can predict changes in MRI-assessed OG size and extension, providing a non-invasive functional assay, complementary to neuro-imaging, for OG follow-up.

Kikuchi-Fujimoto disease (KFD) is a rare and benign disease that typically affects the cervical lymph nodes. Its aetiology is unknown and a role of the autoimmune system in the pathogenesis is hypothesized. This self-limiting disease is often confused with malignancies. No specific management is generally required but long-term follow-up should be planned despite the low risk of recurrence, as recurrences have been described many years after the first episode and there is a high risk of development of an autoimmune disease or even lymphoma. We review the clinical and histological features of KFD and report an unusual case presenting with cervical and supraclavicular lymphadenopathy, and persistent fever

We report a novel case of gray platelet syndrome (GPS). A 14-year-old boy had bleeding diathesis, mild thrombocytopenia, giant platelets with severe defect of alpha-granule secretory proteins, myelofibrosis and splenomegaly.

BACKGROUND: Pain is the most common discomfort experienced by children with cancer and occurs in almost 89% of patients in an advanced stage of the disease. It is most often not adequately treated because of inexperience and unfounded fears of analgesic treatment. In adults, patient controlled analgesia (PCA) is widely administered, while in children with moderate to severe cancer pain its use is still under evaluation for safety and efficacy. GOALS OF WORK: To evaluate the efficacy and safety of fentanyl administered by PCA in children with cancer pain. MATERIALS AND METHODS: Eighteen children (range 6 to 15 years) with moderate to severe pain were enrolled and treated with fentanyl by PCA plus background infusion (BI) (BI of 1 microg/kg/h with booster doses of 1 microg/kg by intravenous route). To evaluate efficacy and safety of the analgesic treatment, different subjective and objective parameters were monitored at 4-h intervals. In addition, patients' satisfaction was assessed by a questionnaire at the end of the treatment. MAIN RESULTS: All children experienced a good degree of analgesia and did not require any other analgesic drug during the treatment. Both subjective and objective parameters improved after starting pain-relieving treatment and no major side effects occurred. The questionnaire administered to the children showed a high grade of satisfaction. CONCLUSIONS: PCA plus BI with fentanyl administered by intravenous route is a safe and efficacious method for analgesia in children with moderate to severe cancer pain. Our policy of fentanyl-treatment did not show any major side effects.

A 3-month-old male infant was admitted to hospital with anemia. Follow-up controls revealed the presence of specific cytomegalovirus (CMV) antibodies. Virus was isolated from urine, blood, and saliva. At 7 months of age, he presented with melena. Polymerase chain reaction (PCR) of biopsy samples from the duodenum was positive for CMV. Anemia resolved after starting antiviral therapy with oral valganciclovir.

No abstract

In pediatric oncology, LPs are frequently performed for diagnostic and therapeutic purposes. A LP procedure may be helpful in diagnosing many diseases and disorders. In addition, a LP may be performed therapeutically, to inject medications directly into the spinal canal. Intrathecal administration of antineoplastic drugs allows to bypass the selective filter of BBB and to achieve significant concentrations of the antineoplastic agents in CSF reducing the likelihood of systemic toxicity. Lumbar puncture is generally well tolerated but might be characterized by several disadvantages and risks.

Children with chronic idiopathic thrombocytopenic purpura generally show a favorable outcome with a high spontaneous recovery rate even many years after the initial diagnosis. In this retrospective study, 5 out of 12 children with chronic ITP achieved a spontaneous recovery. A careful follow-up appears to be adequate for most of the patients, reserving splenectomy to the rare severely affected patients

PURPOSE: The objective of the study was to evaluate the efficacy and toxicity of Temozolomide (TMZ) administered for 5 consecutive days in three daily dosing in children with recurrent or refractory high-grade glioma. PATIENTS AND METHODS: Twenty-four patients with a median age of 10.5 years were enrolled onto this open-label, multicenter, phase II study. The patients were previously treated with surgical resection (17 of 24), radiotherapy (19 of 24) and chemotherapy (18 of 24). Therapy was administered orally three times a day for 5 consecutive days at the dose of 200 mg/m(2)/dx5 for chemotherapy naive patients. In patients heavily pretreated with chemotherapy the starting dose was of 150 mg/m(2)/dx5. RESULTS: A total of 95 cycles were administered. The median progression free-survival (PFS) was 3 months for the entire group while disease stabilization was obtained in 7 patients (29.1%), all with supratentorial tumors. No CR or PR was observed. TMZ treatment showed a limited toxicity. Thrombocytopenia was the most common hematological adverse effect. Our data suggest a marginal activity of TMZ in children with recurrent high-grade glioma.

Rosai-Dorfman disease, or sinus histiocytosis with massive lymphadenopathy (SHML), is a rare and self-limiting benign disorder that most commonly involves the cervical lymph nodes. The authors describe two cases of SHML. Fine-needle aspiration of the lymphadenopathy was performed in both patients. Immunocytochemical and histologic features, as the evidence of emperipolesis and S100 protein positivity on immunostaining, were typical of SHML. Fine-needle aspiration cytology plays an important diagnostic role in SHML and may be conclusive in a typical clinical setting. The diagnosis of SHML should be considered in the differential diagnosis of massive, painless cervical lymphadenopathy. Long-term follow-up is necessary to observe the complete regression of the massive lymphadenopathy. However, specific therapy is available and should be limited to patients with compressive symptoms or extranodal disease.

PURPOSE: The objective of the study was to evaluate the efficacy and toxicity of Temozolomide (TMZ) administered for 5 consecutive days in three daily dosing in children with recurrent or refractory high-grade glioma. PATIENTS AND METHODS: Twenty-four patients with a median age of 10.5 years were enrolled onto this open-label, multicenter, phase II study. The patients were previously treated with surgical resection (17 of 24), radiotherapy (19 of 24) and chemotherapy (18 of 24). Therapy was administered orally three times a day for 5 consecutive days at the dose of 200 mg/m(2)/dx5 for chemotherapy naive patients. In patients heavily pretreated with chemotherapy the starting dose was of 150 mg/m(2)/dx5. RESULTS: A total of 95 cycles were administered. The median progression free-survival (PFS) was 3 months for the entire group while disease stabilization was obtained in 7 patients (29.1%), all with supratentorial tumors. No CR or PR was observed. TMZ treatment showed a limited toxicity. Thrombocytopenia was the most common hematological adverse effect. Our data suggest a marginal activity of TMZ in children with recurrent high-grade glioma.

Hypersensitivity reactions to carboplatin are rare but sometimes life-threatening events may occur requiring discontinuation of treatment. In our study, we describe clinical features and diagnostic procedures of carboplatin-associated reactions in children affected by low-grade astrocytoma and treated with multiple courses of carboplatin. In 6 out of 29 children, we reported allergic events. We also report a desensitization protocol for carboplatin administration, which allowed the patients to receive effective treatment without adverse reactions

Intrathecal chemotherapy with antineoplastic agents is mainly utilised in children with leukaemia and lymphoma, and in selected brain tumours. In these diseases, intrathecal use is restricted to methotrexate (MTX), cytosine arabinoside (Ara-C) and corticosteroids. A number of other agents are, at the present time, under evaluation. Intrathecal MTX administered sequentially with systemic high dose MTX infusion prolongs therapeutic cerebral spinal fluid (CSF) levels of the drug. Prolonged therapeutic CSF levels can also be achieved by giving repeated small intrathecal doses of MTX over an extended period in selected patients, with an implanted Ommaya reservoir. In the CSF, the metabolic inactivation of Ara-C is significantly lower than in plasma with a CSF clearance similar to the rate of CSF bulk flow. A slow-release formulation of Ara-C may be given intrathecally, resulting in a prolonged cytotoxic concentration in the CSF. CNS relapse and neurotoxicity in patients with acute lymphoblastic leukaemia, especially younger children, may be reduced by using age-related dosing of intrathecal MTX and Ara-C. Hydrocortisone is used in combination with MTX and Ara-C for so-called 'triple intrathecal chemotherapy' in the treatment of meningeal leukaemia. Intrathecal thiotepa does not appear to be advantageous over systemic administration in patients with brain and meningeal leukaemia. Monoclonal antibodies, reactive with tumour-associated antigens, can be used as delivery systems for chemotherapeutic agents and radionuclides. However, the development of this new approach is currently under evaluation in larger clinical studies. Neurological adverse effects may be expected with intrathecal chemotherapy and are increased by high dose systemic therapy, concomitant cranial radiotherapy or meningeal infiltration by neoplastic cells. Inadvertant intrathecal administration of antineoplastic agents that are indicated for systemic administration only, is dangerous and may result in a f

Intrathecal chemotherapy with antineoplastic agents is mainly utilised in children with leukaemia and lymphoma, and in selected brain tumours. In these diseases, intrathecal use is restricted to methotrexate (MTX), cytosine arabinoside (Ara-C) and corticosteroids. A number of other agents are, at the present time, under evaluation. Intrathecal MTX administered sequentially with systemic high dose MTX infusion prolongs therapeutic cerebral spinal fluid (CSF) levels of the drug. Prolonged therapeutic CSF levels can also be achieved by giving repeated small intrathecal doses of MTX over an extended period in selected patients, with an implanted Ommaya reservoir. In the CSF, the metabolic inactivation of Ara-C is significantly lower than in plasma with a CSF clearance similar to the rate of CSF bulk flow. A slow-release formulation of Ara-C may be given intrathecally, resulting in a prolonged cytotoxic concentration in the CSF. CNS relapse and neurotoxicity in patients with acute lymphoblastic leukaemia, especially younger children, may be reduced by using age-related dosing of intrathecal MTX and Ara-C. Hydrocortisone is used in combination with MTX and Ara-C for so-called 'triple intrathecal chemotherapy' in the treatment of meningeal leukaemia. Intrathecal thiotepa does not appear to be advantageous over systemic administration in patients with brain and meningeal leukaemia. Monoclonal antibodies, reactive with tumour-associated antigens, can be used as delivery systems for chemotherapeutic agents and radionuclides. However, the development of this new approach is currently under evaluation in larger clinical studies. Neurological adverse effects may be expected with intrathecal chemotherapy and are increased by high dose systemic therapy, concomitant cranial radiotherapy or meningeal infiltration by neoplastic cells. Inadvertant intrathecal administration of antineoplastic agents that are indicated for systemic administration only, is dangerous and may result in a f

Immune tolerance (IT) in hemophilia A patients with anti-factor VIII antibodies is generally based on daily factor VIII administrations. Here we report the preliminary results of an immune tolerance regimen based on recombinant high-dose (400 U/kg) factor VIII boluses administered at 48-hour intervals. Two high responder hemophilia A patients aged 2 and 3 years received this treatment without the need of permanent venous access. In both cases the IT regimen caused an anamnestic response of less than three weeks' duration and an antibody reduction to less than 5 Bethesda units was achieved in about 8-10 weeks. In the child with a more prolonged follow-up the inhibitor became undetectable after four months and factor VIII recovery at 6 months was > 85%. This intermittent high-dose regimen seems to be effective in rapidly inducing immune tolerance and seems particularly suitable for very young children in whom it may be useful to avoid the risks and to reduce the psychological burden of permanent venous access.

Idiopathic thrombocytopenic purpura (ITP) is a relatively common hematologic disease in childhood. ITP is often self-limiting and is characterized by a good clinical outcome. About 10-20% of cases can have a chronic course. In our retrospective analysis we have evaluated 45 patients affected by ITP from January '92 to December '97. Thirty-seven patients (82%) met the criteria of acute ITP and 8 (18%) had chronic ITP. Patients were stratified into 3 categories based up on the type of treatment received: no treatment, steroids, steroids and IVIG. In our series children treated with oral prednisone showed a slightly faster recovery in the first days from treatment. We suggest the use of steroids in children with low platelet count and signs and symptoms of bleeding.

Rhabdoid tumor of the kidney (RTK) is a quite rare malignant neoplasm of early childhood. It has a very unfavourable prognosis, since it tends to give early metastases and shows a poor response to chemotherapy regimens. We report a case of an infant with RTK, who had a rapidly progressive course. Based upon our case and the review of the literature, we would like to stress the importance of a differential diagnosis with another kidney cancer, namely Wilms tumor, which is more frequent and has by far a better prognosis.

A case of congenital defect of factor II is reported. It concerns a newborn with a not traumatic haematoma due to congenital hypoprothrombinaemia, which is rarely described in scientific literature.