Efficacy and safety of intravenous paracetamol in comparison to ibuprofen for the treatment of patent ductus arteriosus in preterm infants: Study protocol for a randomized control trial

Background: Patent ductus arteriosus (PDA) is one of most common complications in preterm infants. Although ibuprofen represents the first choice for the closure of PDA, this treatment can cause severe gastrointestinal and adverse renal effects and worsen platelet function. The successful closure of the PDA with paracetamol has been recently reported in several preterm infants, and the safety of paracetamol for this use has been suggested by the available data. Methods/design: We present the design of a randomized, multicenter, controlled study, whose aim is to assess the effectiveness and safety of intravenous paracetamol in comparison to intravenous ibuprofen for the treatment of PDA in preterm infants. A total of 110 infants born at 25 +0 to 31 +6 weeks of gestational age will be enrolled and randomized to receive paracetamol or ibuprofen (55 patients per group) starting at 24-72h of life. The primary endpoint of the study is the comparison of the PDA closing rate observed after a 3-day course with paracetamol or ibuprofen. The secondary endpoints include the closure rate of PDA after the second course of treatment with ibuprofen, the re-opening rate of the PDA, the incidence of surgical ligation, and the occurrence of adverse effects. Discussion: The results of this study will provide new information about the possible use of paracetamol in the treatment of PDA. Paracetamol could offer several important therapeutic advantages over current treatment options, and it could become the treatment of choice for the management of PDA, mainly due to its more favorable side effect profile. Trial registration: Clinicaltrials.gov NCT02422966. Eudract no. 2013-003883-30

Analysis of HIV quasispecies and virological outcome of an HIV D+/R+ kidney–liver transplantation

Introduction: Transplantation among HIV positive patients may be a valuable therapeutic intervention. This study involves an HIV D+/R+ kidney–liver transplantation, where PBMC-associated HIV quasispecies were analyzed in donor and transplant recipients (TR) prior to transplantation and thereafter, together with standard viral monitoring. Methods: The donor was a 54 year of age HIV infected woman: kidney and liver recipients were two HIV infected men, aged 49 and 61. HIV quasispecies in PBMC was analyzed by ultra-deep sequencing of V3 env region. During TR follow-up, plasma HIV-1 RNA, HIV-1 DNA in PBMC, analysis of proviral integration sites and drug-resistance genotyping were performed. Other virological and immunological monitoring included CMV and EBV DNA quantification in blood and CD4 T cell counts. Results: Donor and TR were all ART-HIV suppressed at transplantation. Thereafter, TR maintained a nearly suppressed HIV-1 viremia, but HIV-1 RNA blips and the increase of proviral integration sites in PBMC attested some residual HIV replication. A transient peak in HIV-1 DNA occurred in the liver recipient. No major changes of drug-resistance genotype were detected after transplantation. CMV and EBV transient reactivations were observed only in the kidney recipient, but did not require specific treatment. CD4 counts remained stable. No intermixed quasispecies between donor and TR was observed at transplantation or thereafter. Despite signs of viral evolution in TR, HIV genetic heterogeneity did not increase over the course of the months of follow up. Conclusions: No evidence of HIV superinfection was observed in the donor nor in the recipients. The immunosuppressive treatment administrated to TR did not result in clinical relevant viral reactivations

Microplastic in wild populations of the omnivorous crab Carcinus aestuarii: A review and a regional-scale test of extraction methods, including microfibres

Microplastic (MP) has become ubiquitous in the marine environment. Its threat to marine organisms has been demonstrated under laboratory conditions, yet studies on wild populations still face methodological difficulties. We reviewed the methods used to separate MP from soft animal tissues and highlighted a lack of standardised methodologies, particularly critical for synthetic microfibres. We further compared enzymatic and a potassium hydroxide (KOH)-based alkaline digestion protocols on wild crabs (Carcinus aestuarii) collected from three coastal lagoons in the north Adriatic Sea and on laboratory-prepared synthetic polyester (PES) of different colour and polypropylene (PP). We compared the cost-effectiveness of the two methods, together with the potential for adverse quantitative or qualitative effects on MP that could alter the capability of the polymers to be recognised via microscopic or spectroscopic techniques. Only 5.5% of the 180 examined crabs contained MP in their gastrointestinal tracts, with a notably high quantitative variability between individuals (from 1 to 117 particles per individual). All MP found was exclusively microfibres, mainly PES, with a mean length (\ub1SE) of 0.5\u202f\ub1\u202f0.03\u202fmm. The two digestion methods provided comparable estimates on wild crabs and did not cause any visible physical or chemical alterations on laboratory-prepared microfibres treated for up to 4 days. KOH solution was faster and cheaper compared to the enzymatic extraction, involving fewer procedural steps and therefore reducing the risk of airborne contamination. With digestion times longer than 4 days, KOH caused morphological alterations of some of the PES microfibres, which did not occur with the enzymatic digestion. This suggests that KOH is effective for the digestion of small marine invertebrates or biological samples for which shorter digestion time is required, while enzymatic extraction should be considered as alternative for larger organisms or sample sizes requiring longer digestion times

Correlates of HCV seropositivity among familial contacts of HCV positive patients

BACKGROUND: Determinants of intrafamilial HCV transmission are still being debated. The aim of this study is to investigate the correlates of HCV seropositivity among familial contacts of HCV positive patients in Italy. METHODS: A cross-sectional study was conducted with 175 HCV positive patients (index cases), recruited from Policlinico Gemelli in Rome as well as other hospitals in Central Italy between 1995 and 2000 (40% female, mean age 57 ± 15.2 years), and 259 familial contacts. Differences in proportions of qualitative variables were tested with non-parametric tests (χ(2), Yates correction, Fisher exact test), and a p value < 0.05 was considered significant. A multivariate analysis was conducted using logistic regression in order to verify which variables statistically have an influence on HCV positivity in contact individuals. RESULTS: Seropositivity for HCV was found in 8.9% of the contacts. From the univariate analysis, risk factors significantly associated to HCV positivity in the contacts were: intravenous drug addiction (p = 0.004) and intercourse with drug addicts (p = 0.005). The only variables associated significantly and independently to HCV seropositivity in patients' contacts were intercourse with drug addicts (OR = 19.28; 95% CI: 2.01 – 184.94), the retirement status from work (OR = 3.76; 95% CI: 1.17 – 11.98), the time of the relationship (OR = 1.06; 95% CI: 1.00 – 1.11) and tattoos (OR = 7.68; 95% CI: 1.00 – 60.20). CONCLUSION: The present study confirms that having intercourse with a drug addict is the most significant risk factor for intrafamilial HCV transmission. The association with retirement status from work could be related to both a long-term relationship with an index case and past exposure to common risk factors

Interferon-α Improves Phosphoantigen-Induced Vγ9Vδ2 T-Cells Interferon-γ Production during Chronic HCV Infection

In chronic HCV infection, treatment failure and defective host immune response highly demand improved therapy strategies. Vγ9Vδ2 T-cells may inhibit HCV replication in vitro through IFN-γ release after Phosphoantigen (PhAg) stimulation. The aim of our work was to analyze Vγ9Vδ2 T-cell functionality during chronic HCV infection, studying the role of IFN-α on their function capability. IFN-γ production by Vγ9Vδ2 T-cells was analyzed in vitro in 24 HCV-infected patients and 35 healthy donors (HD) after PhAg stimulation with or without IFN-α. The effect of in vivo PhAg/IFN-α administration on plasma IFN-γ levels was analyzed in M. fascicularis monkeys. A quantitative analysis of IFN-γ mRNA level and stability in Vγ9Vδ2 T-cells was also evaluated. During chronic HCV infection, Vγ9Vδ2 T-cells showed an effector/activated phenotype and were significantly impaired in IFN-γ production. Interestingly, IFN-α was able to improve their IFN-γ response to PhAg both in vitro in HD and HCV-infected patients, and in vivo in Macaca fascicularis primates. Finally, IFN-α increased IFN-γ-mRNA transcription and stability in PhAg-activated Vγ9Vδ2 T-cells. Altogether our results show a functional impairment of Vγ9Vδ2 T-cells during chronic HCV infection that can be partially restored by using IFN-α. A study aimed to evaluate the antiviral impact of PhAg/IFN-α combination may provide new insight in designing possible combined strategies to improve HCV infection treatment outcome