An infant with hyperalertness, hyperkinesis, and failure to thrive: a rare diencephalic syndrome due to hypothalamic anaplastic astrocytoma.

BACKGROUND: Diencephalic Syndrome is a rare clinical condition of failure to thrive despite a normal caloric intake, hyperalertness, hyperkinesis, and euphoria usually associated with low-grade hypothalamic astrocytomas. CASE PRESENTATION: We reported an unusual case of diencephalic cachexia due to hypothalamic anaplastic astrocytoma (WHO-grade III). Baseline endocrine function evaluation was performed in this patient before surgery. After histological diagnosis, he enrolled to a chemotherapy program with sequential high-dose chemotherapy followed by hematopoietic stem cell rescue. The last MRI evaluation showed a good response. The patient is still alive with good visual function 21 months after starting chemotherapy. CONCLUSIONS: Diencephalic cachexia can rarely be due to high-grade hypothalamic astrocytoma. We suggest that a nutritional support with chemotherapy given to high doses without radiotherapy could be an effective strategy for treatment of a poor-prognosis disease.

Pertussis re-emergence in the post-vaccination era.

BACKGROUND: Resurgence of pertussis in the post-vaccination era has been reported in Western countries. A shift of cases from school-age children to adolescents, adults and children under 1 year of age has been described in the last decade, and mortality rates in infants are still sustained. We aimed to review and discuss the possible vaccination strategies which can be adopted in order to improve the pertussis control, by searches of Pubmed, and websites of US and European Centers for Disease Control and Prevention, between 1st January 2002, and 1st March 2013. DISCUSSION: The following vaccination strategies have been retrieved and analysed: the cocooning strategy, the immunization of pregnant women and newborns, vaccination programs for preschool children, adolescents, adults and health-care workers. Cost-effectiveness studies provide some contrasting data, mainly supporting both maternal vaccination and cocooning. Adolescent and/or adult vaccination seems to be cost-effective, however data from observational studies suggest that this vaccination strategy, used alone, leads to a reduced pertussis burden globally, but does not affect the disease incidence in infants. Moreover, substantial logistical and economic difficulties have to be overcome to vaccinate the largest number of individuals. SUMMARY: The simultaneous use of more than one strategy, including cocooning strategy plus vaccination of adolescents and adults, seems to be the most reasonable preventive measure. The development of new highly immunogenic and efficacious pertussis vaccines continues to be a primary objective for the control of pertussis.

Hearing outcomes and patient satisfaction after stapes surgery: local versus general anaesthesia.

Objective: Otosclerosis is a frequent ear disorder causing a stapedo-ovalar ankylosis and conductive hearing loss. Stapedoplasty, performed under both general (GA) and local anaesthesia (LA), is the most advisable surgical solution. Auditory recovery relies on the patient's conditions and on the intervention itself. The aim of our work was to compare hearing outcomes with stapedoplasty performed under GA or LA and to investigate patients' compliance to both methods. Methods: Fifty-five otosclerotic patients underwent stapedoplasty both under GA (32/55) and LA (23/55). Pre- and post-operative air and bone tone audiometry threshold values as well as the air-bone gap and its closure score, were analysed. All patients filled in a satisfaction questionnaire regarding their concern and level of appreciation of the type of anaesthesia. Results and conclusions: Our data show that the auditory results with stapedoplasty are good and do not differ between LA and GA. Even considering the advantages and limits of the two methods, one cannot favour one or the other type of anaesthesia. Finally, the patient's satisfaction cannot be considered a criterion of choice, since this was found to be high in both cases.

Role of eculizumab in a pediatric refractory gemcitabine-induced thrombotic microangiopathy: a case report.

BACKGROUND: The incidence of gemcitabine-induced hemolytic uremic syndrome has already been described in adults. Several approaches have been employed in the treatment of gemcitabine-induced hemolytic uremic syndrome with different outcomes. One of the most promising agents is eculizumab, which is a monoclonal antibody directed against C5 complement protein. CASE PRESENTATION: We reported the case of a 3-year-old white boy with medulloblastoma who underwent high-dose chemotherapy and craniospinal irradiation. Afterwards he started maintenance chemotherapy with gemcitabine and oxaliplatin. After five courses he presented a progressive clinical worsening, which resulted in a systemic thrombotic microangiopathy. Initially he was treated with rituximab without clinical improvement. Therefore he started therapy with repeated cycles of eculizumab. After seven infusions he showed a gradual improvement and finally a complete remission of gemcitabine-induced hemolytic uremic syndrome. CONCLUSIONS: Eculizumab prevents serious complement-mediated vascular damage for chemotherapy-induced thrombotic microangiopathy in pediatric cases.

Blood-Brain Barrier and Breast Cancer Resistance Protein: A Limit to the Therapy of CNS Tumors and Neurodegenerative Diseases.

The treatment of brain tumors and neurodegenerative diseases, represents an ongoing challenge. In Central Nervous System (CNS) the achievement of therapeutic concentration of chemical agents is complicated by the presence of distinct set of efflux proteins, such as ATP-Binding Cassette (ABC) transporters localized on the Blood-Brain Barrier (BBB). The activity of ABC transporters seems to be a common mechanism that underlies the poor response of CNS diseases to therapies. The molecular characterization of Breast Cancer Resistance Protein (BCRP/ABCG2), as an ABC transporter conferring multidrug resistance (MDR), has stimulated many studies to investigate its activity on the BBB, its involvement in physiology and CNS diseases and its role in limiting the delivery of drugs in CNS. In this review, we highlight the activity and localization of BCRP on the BBB and the action that this efflux pump has on many conventional drugs or latest generation molecules used for the treatment of CNS tumors and other neurodegenerative diseases.

The Use of Anthracyclines for Therapy of CNS Tumors.

Despite being long lived, anthracyclines remain the "evergreen" drugs in clinical practice of oncology, showing a potent effect in inhibiting cell growth in many types of tumors, including brain neoplasms. Unfortunately, they suffer from a poor penetration into the brain when intravenously administered due to multidrug resistance mechanism, which hampers their delivery across the blood brain barrier. In this paper, we summarize the current literature on the role of anthracyclines in cancer therapy and highlight recent efforts on 1) development of tumor cell resistance to anthracyclines and 2) the new approaches to brain drug delivery across the blood brain barrier.

Absence of human cytomegalovirus infection in childhood brain tumors.

Human cytomegalovirus (HCMV) is a common human pathogen which induces different clinical manifestations related to the age and the immune conditions of the host. HCMV infection seems to be involved in the pathogenesis of adult glioblastomas. The aim of our study was to detect the presence of HCMV in high grade gliomas and other pediatric brain tumors. This hypothesis might have important therapeutic implications, offering a new target for adjuvant therapies. Among 106 pediatric patients affected by CNS tumors we selected 27 patients with a positive HCMV serology. The serological analysis revealed 7 patients with positive HCMV IGG (≥14 U/mL), whom had also a high HCMV IgG avidity, suggesting a more than 6 months-dated infection. Furthermore, HCMV IGM were positive (≥22 U/mL) in 20 patients. Molecular and immunohistochemical analyses were performed in all the 27 samples. Despite a positive HCMV serology, confirmed by ELISA, no viral DNA was shown at the PCR analysis in the patients' neoplastic cells. At immunohistochemistry, no expression of HCMV antigens was observed in tumoral cells. Our results are in agreement with recent results in adults which did not evidence the presence of HCMV genome in glioblastoma lesions. We did not find any correlation between HCMV infection and pediatric CNS tumors.

Sexual dimorphism in tuberculosis incidence: children cases compared to adult cases in Tuscany from 1997 to 2011.

BACKGROUND: In most countries, men seem to be more susceptible to tuberculosis (TB) than women, but only few studies have investigated the reasons of this gender incidence difference. The effect of sexual hormones on immunity is possible. METHODS: Data from children and adults, living in Tuscany, hospitalized for TB in all the thirty-one regional hospitals from January 1st 1997 to December 31st 2011, were analyzed using the International Classification of Disease, 9th Revision, Clinical Modification. RESULTS: During the study period, 10,744 patients were hospitalized with TB diagnosis, precisely 279 (2.6%) children [0-14 years], 205 (1.9%) adolescents [15-18 years] and 10,260 (95.5%) adults [≥ 18 years]. The male population ranged from 249 patients (51.4%) in children and adolescents, to 6,253 (60.9%) in adults. Pulmonary TB was the most common form both in children and adults. Men were more likely than women to have pulmonary TB after puberty, while no significant differences were found between males and females in the hospitalized children. The male gender also resulted the most affected for the extra-pulmonary disease sites, excluding the lymphatic system, during the reproductive age. CONCLUSIONS: Our findings suggest a possible role of sexual hormones in the development of TB. No significant male-female difference was found in TB incidence among children, while a sex ratio significantly different from 1:1 emerged among reproductive age classes. An increased incidence difference also persisted in older men, suggesting that male-biased risk factors could influence TB progression. Some limitations of the study are the sample size, the method of discharge diagnosis which could be deficient in accuracy in some cases, the increasing number of immigrants and the lack of possible individual risk factors (smoke and alcohol). Further studies are needed to investigate the possible hormone-driven immune mechanisms determining the sexual dimorphism in TB.

Vaccine effectiveness against severe laboratory-confirmed influenza in children: results of two consecutive seasons in Italy.

OBJECTIVE: To evaluate the effectiveness of seasonal influenza vaccine in preventing Emergency Department (ED) visits and hospitalisations for influenza like illness (ILI) in children. METHODS: We conducted a test negative case-control study during the 2011-2012 and 2012-2013 influenza seasons. Eleven paediatric hospital/wards in seven Italian regions participated in the study. Consecutive children visiting the ED with an ILI, as diagnosed by the doctor according to the European Centre for Disease Control case definition, were eligible for the study. Data were collected from trained pharmacists/physicians by interviewing parents during the ED visit (or hospital admission) of their children. An influenza microbiological test (RT-PCR) was carried out in all children. RESULTS: Seven-hundred and four children, from 6 months to 16 years of age, were enrolled: 262 children tested positive for one of the influenza viruses (cases) and 442 tested negative (controls). Cases were older than controls (median age 46 vs. 29 months), though with a similar prevalence of chronic conditions. Only 25 children (4%) were vaccinated in the study period. The overall age-adjusted vaccine effectiveness (VE) was 38% (95% confidence interval -52% to 75%). A higher VE was estimated for hospitalised children (53%; 95% confidence interval -45% to 85%). DISCUSSION: This study supports the effectiveness of the seasonal influenza vaccine in preventing visits to the EDs and hospitalisations for ILI in children, although the estimates were not statistically significant and with wide confidence intervals. Future systematic reviews of available data will provide more robust evidence for recommending influenza vaccination in children.