State of the art and perspectives in pediatric hepatocellular carcinoma.

Hepatoblastoma (HB) and pediatric hepatocellular carcinoma (HCC) are rare primary malignant liver cancers in children and young adults. HB is the most common and accounts for about 70 % cases; it is usually diagnosed during the first 3 years of life. Instead, pediatric HCC is uncommon, and it is associated with a poor prognosis. Overall, the prognosis of pediatric HCC is dismal with 5-year event-free survival of <30 % as compared to >80 % for HB. Surgery approaches, either resection or transplant, remain the best chance for the cure of pediatric HCC. However, chemotherapy can be helpful as an adjuvant or neoadjuvant treatment. International groups have done trials in pediatric HCC with a chemotherapy regimen, based on cisplatin and doxorubicin (PLADO) as for HB, but the efficacy is limited. Sorafenib, a multi-kinase inhibitor, following positive results in adults and in a pilot study in children, is now tested in conjunction with chemotherapy in the PHITT phase III clinical trial. Some studies have been exploring the genetic profiles of patients to find biological hallmarks that determine the aggressiveness of pediatric HCC. Pathways involved in growth and differentiation are dysregulated and as demonstrated in HB and adult HCC, an important role of the Wnt/CTNNB1 pathway in the pathogenesis of pediatric HCC is also emerging. An extended molecular analysis of tumor samples could give information about pathways as possible targets of biological and immunotherapeutic agents bringing new pharmacological options for the treatment of pediatric HCC.

Environmental Factors in Northern Italy and Sickle Cell Disease Acute Complications: A Multicentric Study.

BACKGROUND: Environmental factors seem to influence clinical manifestations of sickle cell disease (SCD), but few studies have shown consistent findings. We conducted a retrospective multicentric observational study to investigate the influence of environmental parameters on hospitalization for vaso-occlusive crises (VOC) or acute chest syndrome (ACS) in children with SCD. METHODS: Hospital admissions were correlated with daily meteorological and air-quality data obtained from Environmental Regional Agencies in the period 2011-2015. The effect of different parameters was assessed on the day preceding the crisis up to ten days before. Statistical analysis was performed using a quasi-likelihood Poisson regression in a generalized linear model. RESULTS: The risk of hospitalization was increased for low maximum temperature, low minimum relative humidity, and low atmospheric pressure and weakly for mean wind speed. The diurnal temperature range and temperature difference between two consecutive days were determined to be important causes of hospitalization. For air quality parameters, we found a correlation only for high levels of ozone and for low values at the tail corresponding to the lowest concentration of this pollutant. CONCLUSIONS: Temperature, atmospheric pressure, humidity and ozone levels influence acute complications of SCD. Patients' education and the knowledge of the modes of actions of these factors could reduce hospitalizations.

International Latin American Survey on Pediatric Intestinal Failure Team.

There is little data on the experience of managing pediatric Intestinal Failure (IF) in Latin America. This study aimed to identify and describe the current organization and practices of the IF teams in Latin America and the Caribbean. An online survey was sent to inquire about the existence of IF teams that managed children on home parenteral nutrition (HPN). Our questionnaire was based on a previously published European study with a similar goal. Twenty-four centers with pediatric IF teams in eight countries completed the survey, representing a total number of 316 children on HPN. The median number of children on parenteral nutrition (PN) at home per team was 5.5 (range 1-50). Teams consisted of the following members: pediatric gastroenterologist and a pediatric surgeon in all teams, dietician (95.8%), nurse (91.7%), social worker (79.2%), pharmacist (70.8%), oral therapist (62.5%), psychologist (58.3%), and physiotherapist (45.8%). The majority of the centers followed international standards of care on vascular access, parenteral and enteral nutrition, and IF medical and surgical management, but a significant percentage reported inability to monitor micronutrients, like vitamins A (37.5%), E (41.7%), B1 (66.7%), B2 (62.5%), B6 (62.5%), active B12 (58.3%); and trace elements-including zinc (29.2%), aluminum (75%), copper (37.5%), chromium (58.3%), selenium (58.3%), and manganese (58.3%). Conclusion: There is wide variation in how IF teams are structured in Latin America-while many countries have well-established Intestinal rehabilitation programs, a few do not follow international standards. Many countries did not report having an IF team managing pediatric patients on HPN.

Free Radical Production in the Smoking of E-Cigarettes and their Possible Effects in Human Health.

BACKGROUND: The increase in smoking e-cigarettes with nicotine or only flavoring compounds requires a deep study on consequences on human health. This research aims to study the possible process, to form free radicals or the nuclei's damages with consequent micronuclei's formation. METHODS: The study analyzed three groups: the first one that uses e-cigarettes with nicotine, (e-nicotine), the second flavoured liquid (e-vapor) and third the not-smoking group. We determinated the salivary malondialdehyde (MDA), the total salivary mucins (SM). and in buccal smear cells the micronuclei (MN). We statistically analyzed the results with the Mann-Whitney U Test Calculator. RESULTS: Smoking e-cigarettes e-nicotine or e-vapor produced a great and significative amount of MDA vs control group: p ≤ 0.05. Only those smoking e-nicotine, have a highest and statically significant amount of salivary mucins vs control group: P value 00496. In both smokers groups, the mean of MN scores has a significant difference vs control group P ≤ 0.05. CONCLUSIONS: This study shows the possible damages of the nuclei, but the increase of radicals, oral mucins and MN needs more researches.

Micronucleus Test for Diagnosing Uncertain Cases (BI-RADS 3) in Breast Cancer Screening: A Review and Preliminary Results.

INTRODUCTION: BI-RADS in mammography screening is the guide to give a standardized terminology in mammary images. The BI-RADS 3 (uncertain cases) protocol requires anew mammography after six months. This matter of time usually generates much concern and anxiety in patients and in the Radiologists. The aim of this study is to show that using the test of micronuclei (MN) in exfoliated mucosa buccal cells a very early diagnosis is achieved. MATERIAL AND METHODS: We performed an extensive search on Pub Med for "micronuclei in exfoliated buccal cells in breast cancer "and micronuclei in breast cancer". We looked for the keywords in free text and with the cross-referencing method application. We experimentally got samples of buccal mucosa cells from twenty women BI-RADS 3 and twenty women BI-RADS 2. We fixed the samples with Papanicolaou staining. We registered the percentage of the cells containing MN in a total of 500 cells for each sample. The U Mann Whitney Calculator is the test for the statistical analysis of the results. RESULTS: Many studies showed that breast cancer produced MN both in exfoliated cells and in needle aspiration. Their score's count was higher than compared to benign cases, while in the peripheral blood lymphocytes, the results for the MN test were not reproducible. In our preliminary study, the mean percentages of MN in buccal mucosa cells of BI-RADS 3 vs BI-RADS2 didn't show a significant difference: p = 0.05. Two samples of BI-RADS 3 group had a much higher count of MN with a mean of 2.91 ±0.09, 2.88 ±0.08, respectively. This case required biopsy despite the in most of the cases of BI-RADS 3 investigated, the MN test confirmed their benignity. DISCUSSION: In literature, several studies have shown that the genetic damage in breast cancer cells results in MN increased production. Our research showed that in some cases of BI-RADS 3 there was a great increase in MN level. This fact happens in the patients who have taken oestrogens for many years. This therapy is definitely a strong risk factor for breast cancer development because the excesses of any type of hormones interacts with normal breast cell differentiation process. This BI-RADS 3 situation needs further investigation. CONCLUSION: It's interesting to apply the MN scoring in BI-RADS3 because in some cases this test can expect a cancer diagnosis by at least six months' time because, in the other cases, test result can reassure both patient and Radiologists who will wait for the next following checkup with no anxiety.

Cellular immune activation in Sardinian middle-aged, older adults and centenarians.

In addition to viral infections, malignant disorders, autoimmune diseases, and allograft rejection episodes, neopterin increases in older people where it is found to be predictive of overall mortality. Thus, the serum concentrations of this biomarker of systemic immune and inflammation activation, were measured in a small cohort of Sardinian middle-aged, older adults and centenarians. There was a significant positive correlation between neopterin concentrations and age with the subjects in the 95-year-old group with the highest values. Notably, the group of centenarians had neopterin values comparable to those of 80- and 90-year-old groups, and significantly lower than that of 95-year-old group. This suggests a decreased monocyte/macrophage-mediated immune activation and an apparently preserved immune status in centenarians.

Spontaneous Dissemination in Neighboring Provinces of DKA Prevention Campaign Successfully Launched in Nineties in Parma's Province.

AIM: to investigate how much effectiveness of the historical campaign of DKA prevention at T1D diagnosis has survived in Parma's province where this was launched in Nineties, and how much it has spontaneously spread in the neighboring provinces. METHOD: children aged 6-14 years with newly diagnosed TID coming from province of Parma (Group 1) and from two other nearby provinces (Group 2)  were investigated. Clinical and laboratory data were retrospectively collected from medical files of each patient and included age, gender, capillary pH, serum bicarbonate, 3-beta-hydroxybutyrate (3HB), glycated hemoglobin (HbA1c) at the time of admittance from 1st January 2012 and 31 December 2016. RESULTS: no DKA condition was globally found in 25/36 patients (69.4%): 16/17  and 9/19 patients  belonged to Group 1 and 2 respectively (p=0.002). Mild or moderate DKA was reported in 5.9% patients of Group 1 and in 47.31%  (p=0.005) patients from Group 2. Severe DKA was observed in only 1 child from Group 2. Normal 3-beta-hydroxybutyrate (3HB) serum levels was reported in the 25 patients without DKA at diabetes diagnosis. Duration of hyperglycemia-related symptoms before overt T1D diagnosis was shorter (4.6±2.5 days) in patients with 3HB levels <1 mmol/dl  than in those with 3HB levels exceeding  1 mmol/dl (9.6±4.2 days, p< 0.0001). HbA1c values were on overage lower in patients without DKA (9.9±1.2%) than in patients with DKA at diabetes diagnosis (13.60±1.3%; p< 0,001). CONCLUSION: 1) the campaign for DKA prevention, launched  in Nineties and renewed at beginning of Twenties in Parma's province,  continues to be effective in the same province after several years; 2) in the two control provinces despite no information campaign being officially promoted in loco, an unexpected decrease in severe DKA incidence as well a shorter latency before overt T1D diagnosis were  observed in the same  period.

A new HPLC method for serum neopterin measurement and relationships with plasma thiols levels in healthy subjects.

Neopterin, a pyrazinopyrimidine compound, serves as a marker of cellular immune system activation, and it can be used as a prognostic predictor for certain types of diseases. We propose a new simple HPLC method to measure serum neopterin with highly sensitive fluorimetric detection. After TCA serum protein precipitation, the supernatant was diluted five times, injected into a C18 reversed-phase column and eluted at a flow rate of 1.5 mL/min by an isocratic water-acetonitrile (99:1) mobile phase. The natural fluorescence of the molecule was detected at excitation wavelength 353 nm and emission 438 nm. In these conditions the neopterin retention time was about 4 min. Our proposed method was compared with a validated chromatographic separation, and the obtained data of the serum neopterin from 35 healthy volunteers were analysed by Passing-Bablok regression and Bland-Altman test. Neopterin measurement in healthy subjects was also employed to investigate on its potential relationships with plasma thiols levels.