Carmine Tinelli

Background and Objectives Busulfan (Bu) is an old drug, but is still well recommended as an alkylating agent during conditioning therapy, before hematopoietic stem cell transplantation. Although its dose administration is standardized and based on patient weight, therapeutic drug monitoring is required in order to maintain its exposure [as area under the concentration-time curve (AUC) from 0 to infinity AUC_0–∞] within a narrow therapeutic range and, if necessary, to adjust the dose with as short a lead time as possible. The aim of the study is to evaluate the agreement (as calculated AUC) between a gold standard analytical method and a new one that is faster and easier. Methods We analyzed 221 plasma samples from 37 children (0.25–16 years; 4–62.5 kg) and 11 adults (21–59 years; 45–80 kg), corresponding to 52 AUC values (ng h/mL). The drug exposure was calculated, simultaneously, by two validated analytical methods. The reference method was a high-performance liquid chromatography (HPLC) assay combined with an ultraviolet detector (UV). The test method had a triple quadrupole mass spectrometer (MS) as detector; the clean-up procedures of the samples were different and faster. Results The agreement between the two methods (reference and test) was evaluated in terms of Bu exposure differences based on Lin’s concordance correlation coefficient (CCC) and represented by the Bland–Altman plot. The CCC between the AUC of the two methods was excellent (0.868; 95% CI: 0.802–0.935). The precision of the measures (expressed by Pearson's italic "r") was 0.872, and the accuracy (accounted by the bias correction factor) was 0.996. Conclusions We can conclude that the HPLC–MS/MS assay represents a very good alternative to the reference.

BACKGROUND: The Ehlers-Danlos Syndrome (EDS) is a rare disorder affecting the connective tissue. EDS patients may suffer of proprioception and balance impairment but all the studies dealing with such symptoms have been addressed to adult subjects. The Study of such impairment in younger patients may lead to a better awareness of own motor abilities and to a focused rehabilitative intervention. Therefore, our work aims to assess the occurrence of these alterations in a pediatric cohort of EDS patients. METHODS: The Research was designed as a cross-sectional study with a matching control group and performed on a pediatric cohort of 12 subjects with Ehlers-Danlos Syndrome (Classic and Hypennobility type) and on 12 healthy controls, during a follow-up visit at the Department of Pediatrics and at the Rehabilitation Unit of the Foundation IRCCS Policlinico San Matteo, in Pavia from April 2015 to October 2015. A square forceplatform was used to obtain the CoP (center of pressure) displacement during quiet standing during an open and a closed eyes trials. The comparisons between EDS and control group were performed using a t-test for independent data. P<0.05 was considered statistically significant. All tests were two-sided. RESULTS: All the postural parameters considered raised at closed eyes, no significant modifications without vision were found only for the standard deviation along the antero-posterior (AP) axis for the two groups. Both at open eyes and at closed eyes, Patients with EDS showed the postural parameters significantly greater than controls (P <= 0.05) and this observation was most notably for the Sway. CONCLUSIONS: According to our results, a planned monitoring of age-related changes in postural parameters of patients with EDS could be really interesting to provide a perspective of the development of postural control in these patients. In fact, considering our results, it could be interesting to apply rehabilitative strategies to enhance motor coordination and postural reflexes so improving their postural control as soon as possible. Further studies about the postural control in EDS children and adolescents are required to confirm our results.

Pediatric ARDS still represents a difficult challenge in Pediatric Intensive Care Units (PICU). Among different treatments proposed, exogenous surfactant showed conflicting results. Aim of this multicenter retrospective observational study was to evaluate whether poractant alfa use in pediatric ARDS might improve gas exchange in children less than 2 years old, according to a shared protocol. The study was carried out in fourteen Italian PICUs after dissemination of a standardized protocol for surfactant administration within the Italian PICU network. The protocol provides the administration of surfactant (50 mg/kg) divided in two doses: the first dose is used as a bronchoalveolar lavage while the second as supplementation. Blood gas exchange variations before and after surfactant use were recorded. Sixty-nine children, age 0–24 months, affected by Acute Respiratory Distress Syndrome treated with exogenous porcine surfactant were enrolled. Data collection consisted of patient demographics, respiratory variables and arterial blood gas analysis. The most frequent reasons for PICU admission were acute respiratory failure, mainly bronchiolitis and pneumonia, and septic shock. Fifty-four children (78.3%) had severe ARDS (define by oxygen arterial pressure and inspired oxygen fraction ratio (P/F) < 100), 15 (21.7%) had moderate ARDS (100 < P/F < 200). PO2, P/F, Oxygenation Index (OI) and pH showed a significant improvement after surfactant use with respect to baseline (p < 0.001 at each included time-point for each parameter). No significant difference in blood gas variations were observed among four different subgroups of diseases (bronchiolitis, pneumonia, septic shock and others). Overall, 11 children died (15.9%) and among these, 10 (90.9%) had complex chronic conditions. Two children (18.2%) died while being treated with Extracorporeal Membrane Oxygenation (ECMO). Mortality for severe pARDS was 20.4%. The use of porcine Surfactant improves oxygenation, P/F ratio, OI and pH in a population of children with moderate or severe pARDS caused by multiple diseases. A shared protocol seems to be a good option to obtain the same criteria of enrollment among different PICUs and define a unique way of use and administration of the drug for future studies.

Background and Objectives: Celiac disease (CD) is a multifactorial immune-mediated disorder, triggered by the ingestion of gluten in genetically-predisposed subjects carrying MHC-DQ2 and -DQ8 heterodimers, which are encoded by four HLA-DQ allelic variants, overall. This meta-analysis aims at providing further epidemiological support to the predominant relevance of one specific allele, namely HLA-DQB1*02, in the predisposition and genetic risk of CD. Materials and Methods: We performed a search of MEDLINE/PubMed, Embase, Web of Science, and Scopus, retrieving all publications (case–control study, cross-sectional, and retrospective cohort study) on the association between HLA class II polymorphisms and first-degree relatives (FDRs) of children with CD. After a critical reading of the articles, two investigators independently performed data extraction according to the following inclusion criteria: HLA class II genes, any DQ and DR molecules, and CD diagnosed following the current clinical guidelines. A third participant was consulted for discussion to reach an agreement concerning discrepancies. Results: Our search strategy selected 14 studies as being eligible for inclusion, and those were submitted for data extraction and analysis. These studies were published between 1999 and 2016 and, collectively, enrolled 3063 FDRs. Positive and negative likelihood ratios (LR+ and LR−, respectively) for CD diagnosis, according to the presence of the HLA-DQ genotype coding a complete MHC-DQ2 and/or MHC-DQ8 molecules, were 1.449 (CI 1.279–1.642) and 0.187 (CI 0.096–0.362), respectively. If only the isolated presence of HLA-DQB1*02 allele is considered, the pooled estimation of LR+ was 1.659 (CI 1.302–2.155) and, importantly, the LR− still showed a very good discriminatory power of 0.195 (CI 0.068–0.558). Conclusions: Through our differential meta-analysis, comparing the presence of the genotype coding the full MHC-DQ2 and/or DQ8 molecules with the isolated presence of HLA-DQB1*02 allelic variant, we found that the LR− of the latter analysis maintained the same value. This observation, along with previous evidences, might be useful to consider potential cost-effective widened screening strategies for CD in children.

Article: Focused extracorporeal shock wave therapy combined with supervised eccentric training for supraspinatus calcific tendinopathy - European Journal of Physical and Rehabilitation Medicine 2018 February;54(1):41-7 - Minerva Medica - Journals

Article: Vitamin A- and E-based liposomal tear replacement in pediatric patients - Minerva Pediatrica 2017 December;69(6):556-7 - Minerva Medica - Journals

Article: Is retesting in growth hormone deficient children really useful? - Minerva Endocrinologica 2017 December;42(4):325-30 - Minerva Medica - Journals

The aim of this report is to describe the experience in the management of busulphan-based conditioning regimen administered before hematopoietic stem cell transplantation (HSCT) in children.

The role of CD4+CD25highCD127− T-reg cells in solid-organ Transplant (Tx) acceptance has been extensively studied. In previous studies on kidney and liver recipients, peripheral T-reg cell counts were associated to graft survival, while in lung Tx, there is limited evidence for similar findings. This study aims to analyze long term peripheral kinetics of T-reg-cells in a cohort of lung recipients and tests its association to several clinical variables. From jan 2009 to dec 2014, 137 lung Tx recipients were submitted to an immunological follow up (median: 105.9 months (6.7–310.5)). Immunological follow up consisted of a complete blood peripheral immuno-phenotype, inclusive of CD4+CD25highCD127− T and FOXP3+ cells. We tested the association between T-reg and relevant variables by linear OR regression models for repeated measures, adjusting for time from Tx. Also, by ordered logistic models for panel data, the association between Chronic Lung Allograft Dysfuncton (CLAD) onset/progression and T-reg counts in the previous 3 months was tested. Among all variables analyzed at multivariate analysis: Bronchiolitis Obliterans Syndrome (OR −6.51, p < 0.001), Restrictive Allograft Syndrome (OR −5.19, p = 0.04) and Extracorporeal photopheresis (OR −5.65, p < 0.001) were significantly associated to T-reg cell. T-reg cell counts progressively decreased according to the severity of CLAD. Furthermore, patients with higher mean T-reg counts in a trimester had a significantly lower risk (OR 0.97, p = 0.012) of presenting CLAD or progressing in the graft dysfunction in the following trimester. Our present data confirm animal observations on the possible role of T-reg in the evolution of CLAD.