Comparison between actigraphy and parental reporting for sleep assessment in hospitalized infants.

BACKGROUND: Our aim is to compare data obtained through actigraphy with data from parental diaries to evaluate their concordance. METHODS: We enrolled 55 hospitalized infants aged 1-12 months with a gestational age higher than 35 weeks and without sleep disorders, complications due to perinatal events or movement deficits. They were monitored using both methods for 24 hours. Total diurnal and nocturnal sleep times and the numbers of awakenings were evaluated. Actigraph data were analyzed with Sadeh's algorithm. RESULTS: Sleep time was analyzed in 51 infants. The average sleep time was 724.33 (±104.69) minutes according to the diaries and 625.18 (±109.14) minutes according to the actigraphy data, yielding a difference of 99.16 (±97.53) minutes (P<0.0001). The average number of awakenings was 8.65 (±3.78) according to the diaries and 13.43 (±5.09) according to the actigraphy data, with a difference of -4.78 (±4.50) (P<0.0001). A low concordance (≤0.66) was found between the two methods. The two methods provided different results (P<0.05) regarding nocturnal and diurnal sleep. After accounting for differences in disease and feeding types, the actigraphy and diary data were significantly different except for the number of daily awakenings. Concordances were higher in infants with respiratory diseases and those who were breastfed, except for the evaluation of nocturnal sleep. CONCLUSIONS: Concordance between actigraphy and parental reporting is low. Actigraphy may be a useful and easy to use method for collecting data on infants' sleep than a parental diary, but actigraphy data should be analyzed in conjunction with infants' passive movement records.

[Hyperuricemia and gene mutations: a case report].

Hyperuricemia is frequently found in nephrology. The case presented may be useful to clarify some pathogenetic aspects. It is a patient of 18 years, hyperuricaemic. Non-consanguineous parents, hyperuricemia in the paternal line, not neuropsychiatric disorders in the family. Delay in neuromotor acquisitions, average intellectual disabilities, anxiety disorder, obsessive-compulsive personality traits. Normal renal function and renal ultrasound. Evidence of hyperuricemia in 2015. Never gouty episodes and / or lithiasis, initiated allopurinol 100 mg on alternate days, with no side effects, urea in the control range, slightly below normal uricuria. Given the complex clinical, he carried out a genetic analysis of array-CGH. He showed a deletion on the short arm of chromosome 3 (3p12.3) and a duplication of the long arm of chromosome 1 (19q13-42). The deletion 3p12.3 (paternal inheritance), involves the ROBO2 gene. Duplication 19q13.42, (maternal inheritance), includes NLRP12, DPRX, ZNF331 genes. The ROBO2 gene with its mutation, is associated with vesicoureteral reflux. The NLRP12 gene encodes proteins called "Nalps", forming a subfamily of proteins "CATERPILLAR". Many "Nalps" as well as the "Nalps 12" have an N-terminal domain (DYP) with a purin. Since uric acid is a byproduct of purine metabolism, considered the familiarity, we believe that we can hypothesize that the mutations found. In particular those concerning the NLRP-12 gene, may have a role in the presence of hyperuricemia. We believe that in patients with hyperuricemia, associated with a particular impairment of neurological picture, it is likely that there is a subtended common genetic deficiency.

Looking for new treatments of Infantile Colic.

Infantile colic is a common disturbance occurring in the first three months of life. It is a benign condition and one of the main causes of pediatric consultation in the early part of life because of its great impact on family life. Some pediatricians are prone to undervalue this issue mainly because of the lack of evidence based medicine guidelines. Up to now, there is no consensus concerning management and treatment. Literature reports growing evidence about the effectiveness of dietary, pharmacological, complementary and behavioral therapies as options for the management of infantile colic. Dietary approach, usually based on the avoidance of cow's milk proteins in breast-feeding mothers and bottle-fed infants, more recently has seen the rise of new special formulas, such as partially hydrolyzed proteins and low lactose added with prebiotics or probiotics: their efficacy needs to be further documented. Investigated pharmacological agents are Simethicone and Cimetropium Bromide: the first is able to reduce bloating while the second could reduce fussing crying, but it has been tested only for severe infantile colic. No other pain relieving agents have been proposed until now, but some clinical trials are ongoing for new drugs.There is limited evidence supporting the use of complementary and alternative treatments (herbal supplements, manipulative approach and acupuncture) or behavioral interventions.Recent studies have focused the role of microbiota in the pathogenesis of this disturb and so new treatments, such as probiotics, have been proposed, but only few strains have been tested.Further investigations are needed in order to provide evidence-based guidelines.

Quantitative ultrasound applied to metacarpal bone in infants.

Aim. To provide bone status assessment in infancy using quantitative ultrasound (QUS) applied to second metacarpus. Methods. 103 healthy term infants and 3 patients with rickets, aged ≤ 12 months, underwent metacarpal QUS evaluation using QUS DBM Sonic Aurora IGEA (MO, Italy), which measures speed of sound (mcSOS) and bone transmission time (mcBTT). Results. In the total sample, median (interquartile range) of mcSOS was 1640.00 (26.0) m/s and mcBTT 0.82 (0.21) µs. Moreover, reference values for age were obtained based on estimation of the lower and upper percentiles. We observed a statistical significant difference between groups of age for mcSOS (p = 0.016). In a multiple linear regression model, we found a relation between age at enrolment and mcSOS (ß = -0.608; p = 0.000) and mcBTT (ß = -0.819; p = 0.001). A positive correlation between mcSOS and mcBTT has been observed (r = 0.631; p = 0.000). All the patients with rickets showed values of mcSOS and mcBTT lower than the 10th percentile. Conclusion. Our findings show that this new simple technique appears to be a promising tool for monitoring bone mineral status in pediatric clinical practice and in early life. Furthermore, it could be considered a useful method to investigate and to monitor the role of different factors on programming of bone health and it should be tested as a new method for monitoring subjects with rickets during therapy.

Functional evaluation of circulating hematopoietic progenitors in Noonan syndrome.

Noonan syndrome (NS) is an autosomal dominant disorder, characterized by short stature, multiple dysmorphisms and congenital heart defects. A myeloproliferative disorder (NS/MPD), resembling juvenile myelomonocytic leukemia (JMML), is occasionally diagnosed in infants with NS. In the present study, we performed a functional evaluation of the circulating hematopoietic progenitors in a series of NS, NS/MPD and JMML patients. The different functional patterns were compared with the aim to identify a possible NS subgroup worthy of stringent hematological follow-up for an increased risk of MPD development. We studied 27 NS and 5 JMML patients fulfilling EWOG-MDS criteria. The more frequent molecular defects observed in NS were mutations in the PTPN11 and SOS genes. The absolute count of monocytes, circulating CD34+ hematopoietic progenitors, their apoptotic rate and the number of circulating CFU-GMs cultured in the presence of decreasing concentrations or in the absence of granulocyte-macrophage colony-stimulating factor (GM-CSF) were evaluated. All JMML patients showed monocytosis>1,000/µl. Ten out of the 27 NS patients showed monocytosis>1,000/µl, which included the 3 NS/MPD patients. In JMML patients, circulating CD34+ cells were significantly increased (median, 109.8/µl; range, 44-232) with a low rate of apoptosis (median, 2.1%; range, 0.4-12.1%), and circulating CFU-GMs were hyper-responsive to GM-CSF. NS/MPD patients showed the same flow cytometric pattern as the JMML patients (median, CD34+ cells/µl, 205.7; range, 58-1374; median apoptotic rate, 1.4%; range, 0.2-2.4%) and their circulating CFU-GMs were hyper-responsive to GM-CSF. These functional alterations appeared 10 months before the typical clinical manifestations in 1 NS/MPD patient. In NS, the CD34+ absolute cell count and circulating CFU-GMs showed a normal pattern (median CD34+ cells/µl, 4.9; range, 1.3-17.5), whereas the CD34+ cell apoptotic rate was significantly decreased in comparison with the controls (median, 8.6%; range, 0-27.7% vs. median, 17.6%; range, 2.8-49.6%), suggesting an increased CD34+ cell survival. The functional evaluation of circulating hematopoietic progenitors showed specific patterns in NS and NS/MPD. These tests are a reliable integrative tool that, together with clinical data and other hematological parameters, could help detect NS patients with a high risk for a myeloproliferative evolution.

In vitro anti-neuroblastoma activity of saquinavir and its association with imatinib.

Neuroblastoma (NB) has a poor prognosis when in advanced stages, highlighting the need for new therapeutic options. The human immunodeficiency virus (HIV) protease inhibitor saquinavir is active in vitro against chronic myeloid leukaemia cells, in synergy with the tyrosine kinase inhibitor imatinib. Here, we evaluated the effects of saquinavir, alone or in association with imatinib, on cell proliferation (count of viable cells after trypan blue exclusion), apoptosis (Annexin V binding) and invasion (through a transwell membrane coated with Matrigel) in SJ-N-KP, IMR5, AF-8, SK-N-SH and SK-N-BE NB lines, all expressing c-kit and PDGF-R (determined by flow cytometry). Saquinavir showed a dose-dependent anti-proliferative and anti-invasive activity on NB lines, increased by the association with imatinib when the two drugs were utilized at clinically attainable concentrations. The same low saquinavir concentrations inhibited in NB cells the nuclear activation of NF-κB (Western immuno-blotting for nuclear NF-κB p50 and p65). Saquinavir at high concentrations also exerted a pro-apoptotic activity on NB lines, significantly increased by the association with imatinib. In conclusion, saquinavir and imatinib are both drugs utilized for long-term therapies, with good oral bioavailability and a well-known toxicity profile. The anti-NB activity of saquinavir and of its association with imatinib suggests a potential usefulness in the treatment of NB, particularly for remission maintenance.

Marriage and parenthood among childhood cancer survivors: a report from the Italian AIEOP Off-Therapy Registry.

BACKGROUND: The aim of this study was to describe the patterns of marriage and parenthood in a cohort of childhood cancer survivors included in the Off-Therapy Registry maintained by the Italian Association of Pediatric Hematology and Oncology. DESIGN AND METHODS: We analyzed a cohort of 6,044 patients diagnosed with cancer between 1960 and 1998, while aged 0 to 14 years and who were 18 years old or older by December 2003. They were followed up through the regional vital statistics registers until death or the end of follow up (October 30, 2006), whichever occurred first, and their marital status and date of birth of their children were recorded. The cumulative probabilities of being married and having a first child were computed by gender and compared by tumor type within the cohort. Marriage and fertility rates (the latter defined as the number of live births per woman-year) were compared with those of the Italian population of the same age, gender, area of residence and calendar period by means of the observed to expected (O/E) ratios. RESULTS: During the follow-up period, 4,633 (77%) subjects had not married. The marriage O/E ratios were 0.56 (95% CI: 0.51-0.61) and 0.70 (95% CI: 0.65-0.76) among men and women, respectively. Overall, 263 men had 367 liveborn children, and 473 women had 697 liveborn children. The female fertility O/E ratio was 0.57 (95% CI: 0.53-0.62) overall, and 1.08 (95% CI: 0.99-1.17) when analyses were restricted to married/cohabiting women CONCLUSIONS: Childhood cancer survivors are less likely to marry and to have children than the general population, confirming the life-long impact of their previous disease on their social behavior and choices. The inclusion of counseling in the strategies of management and long-term surveillance of childhood cancer patients could be beneficial to survivors as they approach adulthood.

Ultrasound screening for thyroid carcinoma in childhood cancer survivors: a case series.

CONTEXT: Childhood cancer survivors need regular monitoring into young adulthood and beyond, because they are at risk for developing late-onset complications of cancer therapy, including second malignancies. OBJECTIVE: This study focuses on the use of thyroid ultrasound to screen for thyroid carcinoma in a population of childhood cancer survivors. PATIENTS: A total of 129 subjects who had received radiotherapy to the head, neck, or upper thorax for a pediatric cancer were studied in the setting of a long-term follow-up unit. DESIGN: Thyroid ultrasound usually began 5 yr after radiotherapy and was repeated every third year, if negative. Median follow-up time since childhood cancer diagnosis was 15.8 yr (range 6.1-34.8 yr). Solid thyroid nodules were found in 35 patients. Fine-needle aspiration was performed in 19 patients, of which 14 had nodules above 1 cm. MAIN OUTCOME MEASURE: The main outcome measure was the finding of not palpable thyroid cancers. RESULTS: Cytological examination of specimens diagnosed papillary carcinoma in five patients who underwent surgery. The cytological diagnosis of papillary thyroid carcinoma was confirmed in all cases by histological examination. Notably, only two of these patients had palpable nodules; the other three were smaller than 1 cm and were detected only by ultrasound. However, histological examination showed nodal metastases in two of these. CONCLUSIONS: Although ultrasound screening for thyroid cancer in the general population is not cost effective and could lead to unnecessary surgery, due to false positives, we believe that in childhood cancer survivors who received radiotherapy involving the head, neck, or upper thorax, it would be worthwhile.

In vitro antiproliferative and antimigratory activity of dasatinib in neuroblastoma and Ewing sarcoma cell lines.

Neuroblastoma (NB) and Ewing sarcoma (ES) are neuroectodermal tumors typical of pediatric age that, despite aggressive treatment, still present a poor prognosis when in advanced stages. Studies indicate that c-KIT and platelet-derived growth factor receptor (PDGFR) play a substantial role in the proliferation and survival of NB and ES cells. Dasatinib, an oral multi-targeted inhibitor of several kinases including BCR-ABL and SRC-family kinases, is also active against c-KIT and PDGFR. Here, we evaluated the effect of dasatinib on the NB cell lines SJ-N-KP, SK-N-BE, AF8 and IMR5, and on the ES lines PDE02, TC106 and 6647. Proliferation and viability assays showed that dasatinib exerts an antiproliferative activity with a peak effect occurring at 24 h. After a 24-h exposure to dasatinib at 100 nM, proliferation was inhibited by 29.4+/-5.7% in SJ-N-KP, 41.3+/-11.7% in IMR5, 35.3+/-7.6% in PDE02 and 14+/-10.6% in 6647. Dasatinib did not induce apoptosis in NB and ES cell lines. A possible antimigratory activity of dasatinib was evaluated by scratch test. Dasatinib at 100 nM inhibited the migration of NB and ES cell lines by a mean of 30.2 and 25.3%, respectively. This activity suggests a possible role of dasatinib in inhibiting metastasis and appears of particular interest, given the association between metastatic disease and poor prognosis in these tumors. In conclusion, the cytostatic and antimigratory activity of dasatinib in NB and ES cell lines and the lack of pro-apoptotic activity suggests a possible use for this compound in the treatment of these tumors as a combination with other cytotoxic therapy.

Multilineage engraftment of refrozen cord blood hematopoietic progenitors in NOD/SCID mice.

Seven cord blood (CB) units were tested for their capacity to repopulate irradiated NOD/SCID mice after one or two successive cryopreservation procedures. In primary transplants with frozen or refrozen CB cells we observed equivalent human colonies and percentages of human CD45+ cells, with multilineage engraftment. In secondary transplants flow cytometry and polymerase chain reaction for the a satellite region of chromosome 17 showed equivalent levels of human engraftment. Since CB units have, to date, mainly been stored in individual bags, our results suggest new options for optimizing the timing of infusions of expanded and non-expanded progenitors in transplants.

Disseminated neuroblastoma in children older than one year at diagnosis: comparable results with three consecutive high-dose protocols adopted by the Italian Co-Operative Group for Neuroblastoma.

PURPOSE: To compare the outcomes associated with modifications in three consecutive protocols employed by the Italian Co-Operative Group for Neuroblastoma (ICGNB) in disseminated neuroblastoma. PATIENTS AND METHODS: Between January 1985 and November 1997, a total of 359 children aged 1 to 15 years with newly diagnosed stage 4 neuroblastoma were enrolled in three consecutive protocols. Compared with ICGNB-85, the ICGNB-89 protocol contained two more chemotherapy cycles, and some drugs were given at greater doses, whereas in the ICGNB-92 protocol, the induction phase included a chelating agent, and individual cycles contained four drugs instead of two. RESULTS: A total of 330 of 359 evaluable children were included in this analysis; 106 children were treated with ICGNB-85, 65 children were treated with ICGNB-89, and 159 children were treated with ICGNB-92 protocols. Radical resection of primary tumor was carried out in 59.4%, 50.8%, and 57.9% of the patients, respectively. Major tumor response after induction therapy was achieved in 66.7%, 69.2%, and 68.6% of the patients, respectively. A total of 218 of 232 patients received consolidation therapy consisting of conventional chemotherapy in 65 patients and of high-dose chemotherapy in 153 patients. Disease recurrence or progression occurred in 82.1%, 69.2%, and 74.8% of the patients, respectively. Therapy-related deaths occurred in 1.9%, 12.3%, and 6.9% of the patients, respectively. Five-year overall survival (OS) for the three studies was 26%, 23%, and 28%, and event-free survival (EFS) was 19%, 17%, and 17%, respectively. CONCLUSION: The therapeutic modifications adopted in the ICGNB-89 and ICGNB-92 protocols were not associated with a significant improvement in response rate or in the 5-year OS and EFS as compared with the ICGNB-85 protocol. Attempts at intensifying chemotherapy were associated with greater toxicity.

Recovery of cord blood hematopoietic progenitors after successive freezing and thawing procedures.

BACKGROUND AND OBJECTIVES: Cord blood (CB) is a valuable source of stem cells. Most CB units are still cryopreserved in single bags in the world's CB banks. Thawing a single CB unit, dividing it into two parts, expanding the smaller one and refreezing the other would optimize ex vivo expansion of CB progenitors prior to transplantation: expanded and unexpanded cells could be infused together to accelerate early engraftment. DESIGN AND METHODS: The feasibility of refreezing CB samples was investigated by evaluating the effect of 3 successive cryopreservation procedures in 9 CB units. The number and viability of WBC, BFU-E, CFU-GM, CFU-MIX, LTC-IC, and the absolute CD34+ cell count were assessed at time 0 and after each thawing. The percentage of CD34 cells expressing CD38, L-selectin, VLA-4, VLA-5, H-CAM, LFA-1 and CXCR4 was also evaluated. RESULTS: After three freezing and thawing procedures, WBC counts decreased, while lymphocytes were unchanged. Viability was 90% of basal values after the first thawing and did not change. BFU-E decreased significantly only after the third thawing. CFU-GM and CFU-MIX did not change significantly, nor did LTC-IC, CD34+ cell counts and CAM and CXCR4 expression on CD34+/ CD38-- cells. INTERPRETATION AND CONCLUSIONS: These data show that two successive freeze-thaw procedures do not significantly affect the clonogenic potential and CAM expression of cord blood progenitors. This information could be exploited to devise new options in ex vivo expansion procedures and quality controls prior to transplantation.