Neuroblastic tumors and neurofibromatosis type 1: A retrospective multicenter study in Italy and systematic review of the literature.

Background: Neuroblastic tumors (NBTs) are the most common extra-cranial solid tumors of childhood. Neurofibromatosis type 1 (NF1) is the most common neurocutaneous disorder with a predisposition to tumors. The co-occurrence of NBTs in the setting of NF1 has been occasionally reported, suggesting a non-casual association and likely configuring a spectrum of neural crest-derived disorders. Aim of the study: To explore the occurrence of NBTs within NF1 and to report on its natural history, therapeutic strategies, and outcomes in an Italian cohort of children with NF1 and in the literature. Subjects and Methods: Study (a): a retrospective analysis of questionnaire-based data [years 1979-2017] derived from the databases of the Italian Registry for Neuroblastoma (RINB) of the Italian Society of Pediatric Onco-Haematology (AIEOP); and Study (b): a systematic review search on NF1/NB co-occurrence. Results: Study (a) identified eight children with NBTs, 0.2% of patients registered in the RINB, fulfilling the diagnostic criteria for NF1. The primary site of NBTs was abdominal in six patients. The NBTs were neuroblastoma (NB) in five patients, ganglioneuroblastoma (GNB) in one, patient, and ganglioneuroma (GN) in two. Metastatic diffusion occurred in three out of eight children. MYCN gene testing, performed in the tumors of five patients, resulted not-amplified. The major features of NF1 included the following: NF1 family history in four patients, café-au-lait spots in all, freckling in six, Lisch nodules in three, and neurofibromas in three. With regard to the outcome, four children survived three of these for the progression of NB and one for a second tumor. Study (b) identified 12 patients with NF1/NB from the years 1966-2017, and the median age at diagnosis was 27 months (range = 0-168 months). The primary site of NB was thoracic. The prevalent histotype was NB in nine patients, GNB in two, and GN in one. Eight/nine NBs were metastatic. The MYCN gene was amplified in the only studied case. The NF1 features included NF1 family history in seven patients; the major NF1 features were café-au-lait spots in nine patients, freckling in one, Lisch nodules in none, and neurofibromas in six. The outcome was good for only two children, while eight children died of neuroblastoma, at a median age of 49.5 months (range = 2.4-174 months), with a median survival time of 21.75 months after diagnosis. Conclusions: To our knowledge, this represents the first systematic study on the occurrence of NBTs in NF1. This confirms that NBs are rare per se in the setting of NF1 (0.2% of all NBs) and even if compared to the overall frequency of malignancies in NF1 (i.e., 14.7%). The male:female ratio in study (a) (0.6) was different from what was recorded in study (b) (1.5) and in line with the overall increased frequency of malignancies in females with NF1. The median ages at diagnosis of NB in either study (a) or (b) were concordant with what occurred in the NB population. In study (a) versus study (b), the frequency of metastatic diffusion was lower, likely indicating less awareness on work-ups for malignancies in old NF1 series in the literature. The outcome was much better in study (a) than in study (b), indicating that multidisciplinary treatment for NB is highly recommended.

Pulse Oximetry Saturation (Spo2) Monitoring in the Neonatal Intensive Care Unit (NICU): The Challenge for Providers: A Systematic Review.

BACKGROUND: In the neonatal intensive care unit (NICU), maintaining an oxygenation level that avoids both hypoxemia and hyperoxemia is challenging. Pulse oximetry has become fundamental for noninvasive monitoring of saturation of peripheral oxygen (Spo2) in preterm newborns. PURPOSE: The aim of this systematic review is to determine Spo2 target values in order to avoid hypoxemia or hyperoxemia and complications arising from these. METHOD AND SEARCH STRATEGY: For this systematic review, articles were audited from 2010 to 2020 using the PRISMA guidelines. PubMed, MEDLINE, Google Scholar, and Scopus databases were used, and search terms were related to use of pulse oximetry in the NICU. RESULTS: The result showed that 12 of 20 (60%) studies focused on target values but without a unanimous agreement on values, although 5 of 12 studies (41.66%) suggested a lower value target of 85% and 4 of 12 studies (33.33%) recommended 95% as the higher target value. Other authors showed no difference in the incidence of adverse events comparing different target values and focused the importance more on the fluctuation of the value than on the target value itself. IMPLICATION FOR PRACTICE: Reaching a balance in the oxygen administration so as to avoid potential complications associated with hypoxemia or hyperoxemia is a challenge for the clinicians. IMPLICATION FOR RESEARCH: Further studies on fluctuation of Spo2 comparing different starting targets could better clarify the role of fluctuations and the absolute target values.Video Abstract available at:https://journals.na.lww.com/advancesinneonatalcare/Pages/videogallery.aspx?autoPlay=false&videoId=49.

Observational study on the efficiency of Neonatal Emergency Transport in reducing mortality and morbidity indexes in Sicily.

In these last 25 years, the Neonatal Emergency Transport (NET) service has been widely improved in Italy. To date, all National areas are covered by a NET service; 53 NET centers have been activated in all the Italian territory. Herein, the authors present an observational study to evaluate the rate of infantile mortality after introduction of NET in Sicily, and to study the efficiency of this service in reducing these rates of mortality in vulnerable neonates, transported from primary care birth centers to tertiary facilities to undergo to specialized NICU assistance. All neonates who required an emergency transport by NETS were included. No exclusions criteria were applied. Demographic and regional infantile mortality data, expressed as infant mortality rate, were selected by the official government database (ISTAT- National Statistic Institute- http://www.istat.it ). All data were respectively divided into three groups: data concerning transport, clinical condition, and mortality of the transported patients. We transported by NET 325 neonates. The analysis of the infant mortality rate (per 1.000 live births) in Catania from 2016 to 2018 was reduced compared to the same rate calculated before NETS activation (4.41 index before 2016 vs 4.17 index after 2016). These data showed an increase in other provinces (Enna, Caltanissetta, and Agrigento). 61% of neonates showed a respiratory disease. During the study period the proportion of neonates with a Mortality Index for Neonatal Transportation-MINT < 6 has been reduced, while there was an increase of neonates with higher Transport Risk Index of Physiologic Stability-TRIPS score results. The slight decrease of infantile mortality in Catania during the first three years after introduction of NET follows the same trend of all Italian territories, showing the importance of this service in reducing infantile mortality.

Oxidative Stress in Preterm Infants: Overview of Current Evidence and Future Prospects.

Preterm birth (PTB), defined as parturition prior to 37 weeks of gestation, is the leading cause of morbidity and mortality in the neonatal population. The incidence and severity of complications of prematurity increase with decreasing gestational age and birthweight. The aim of this review study is to select the most current evidence on the role of oxidative stress in the onset of preterm complication prevention strategies and treatment options with pre-clinical and clinical trials. We also provide a literature review of primary and secondary studies on the role of oxidative stress in preterm infants and its eventual treatment in prematurity diseases. We conducted a systematic literature search of the Medline (Pubmed), Scholar, and ClinicalTrials.gov databases, retroactively, over a 7-year period. From an initial 777 articles identified, 25 articles were identified that met the inclusion and exclusion criteria. Of these, there were 11 literature reviews: one prospective cohort study, one experimental study, three case-control studies, three pre-clinical trials, and six clinical trials. Several biomarkers were identified as particularly promising, such as the products of the peroxidation of polyunsaturated fatty acids, those of the oxidation of phenylalanine, and the hydroxyl radicals that can attack the DNA chain. Among the most promising drugs, there are those for the prevention of neurological damage, such as melatonin, retinoid lactoferrin, and vitamin E. The microbiome also has an important role in oxidative stress. In conclusion, the most recent studies show that a strong relationship between oxidative stress and prematurity exists and that, unfortunately, there is still little therapeutic evidence reported in the literature.

General anesthesia, conscious sedation, or nothing: Decision-making by children during painful procedures.

BACKGROUND: Following diagnosis, children with cancer suddenly find themselves in an unknown world where unfamiliar adults make all the important decisions. Children typically experience increasing levels of anxiety with repeated invasive procedures and do not adapt to the discomfort. The aim of the present study is to explore the possibility of asking children directly about their medical support preferences during invasive procedures. PROCEDURE: Each patient was offered a choice of medical support on the day of the procedure, specifically general anesthesia (GA), conscious sedation (CS), or nothing. An ad hoc assessment tool was prepared in order to measure child discomfort before, during, and after each procedure, and caregiver adequacy was measured. Both instruments were completed at each procedure by the attending psychologist. RESULTS: We monitored 247 consecutive invasive procedures in 85 children and found that children in the 4 to 7 year age group showed significantly higher distress levels. GA was chosen 66 times (26.7%), CS was chosen 97 times (39.3%), and nothing was chosen 5 times and exclusively by adolescents. The child did not choose in 79 procedures (32%). The selection of medical support differed between age groups and distress level was reduced at succeeding procedures. CONCLUSIONS: Offering children the choice of medical support during invasive procedures allows for tailored support based on individual needs and is an effective modality to return active control to young patients, limiting the emotional trauma of cancer and treatment.

Triptorelin for Fertility Preservation in Adolescents Treated With Chemotherapy for Cancer.

BACKGROUND: Triptorelin, a gonadotropin releasing hormone analogue, can be administered to postpubertal female individuals with cancer who receive chemotherapy to obtain menstrual suppression and decrease the risk of hemorrhage caused by thrombocytopenia. Our goal was to assess whether triptorelin also has a protective role against the gonadotoxicity of chemotherapy. PATIENTS AND METHODS: This retrospective observational study includes all postmenarchal female patients who presented to our Unit from 2000 to 2015 and received chemotherapy for cancer. They were administered depot triptorelin. We evaluated long-term ovarian function in order to detect clinical signs of ovarian damage, miscarriages, and pregnancies. Laboratory follow-up consisted in dosing serum follicle stimulating hormone, luteinizing hormone, prolactin, estradiol, and progesterone. Ultrasound of the ovaries was performed as well. RESULTS: Of 36 evaluable patients, 9 received hematopoietic stem cell transplantation (HSCT). The remaining 27 patients maintained normal ovarian function at clinical, laboratory, and ultrasound assessment. Five of them achieved spontaneous physiological pregnancy. Four of the 9 patients who underwent HSCT developed premature ovarian failure. CONCLUSION: Our study suggests that gonadotropin releasing hormone-a administered during chemotherapy can prevent premature ovarian failure in patients treated without HSCT and that it is not enough to preserve the ovarian function during HSCT. Hence, a prospective randomized trial with a larger population would be recommended.