First 70 Days Critical Data Trend for COVID-19 in Four Regions of Northern Italy: A Pilot Study.

The new coronavirus syndrome (COVID-19) is a multi-organ pathological manifestation that, in severe forms, causes greater damage to the respiratory system, especially in the lung district with severe respiratory failure. In many cases, especially in elderly patients with high comorbidity degree, the disease can have a rapid course with a fatal outcome. Specifically, the data relating to the four Italian regions most affected by the effects of the new coronavirus Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2), namely Lombardia, Veneto, Emilia Romagna and Piemonte, were assessed. In this work, we decided to focus the analysis only on data relating to patients admitted to the intensive care unit and to patients who died in Italy with COVID-19 in the period 24 February-4 May 2020. We used a data set where each point was an expression not of a single day, but of a longer period of time (date-points method). The article clearly identifies the phases in which the epidemic was articulated at national level and in the observed regions. Both the overall national data and the data referring to the most affected regions show an initial exponential mortality trend up to March 21st approximately. From this point the restrictive measures adopted from March 10th shows their effects and the trend first increases only linearly and then finally decreases, also thanks to the implementation of therapeutic strategies aimed at modulating respiratory distress and the clinical condition of thromboembolism, typical of critical patient COVID-19.

A Gel Formulation Containing a New Recombinant Form of Manganese Superoxide Dismutase: A Clinical Experience Based on Compassionate Use-Safety of a Case Report.

Background. We report a case of bilateral posterior subcapsular cataracts (PSCs) in a 24-year-old man with an allergic conjunctivitis history caused by a long-term therapy with glucocorticoids. Case Presentation. The patient showed a visual acuity of 9/10 for both eyes. He followed a therapy with ketotifen and bilastine for four years. During the last six months before our evaluation, he was treated with chloramphenicol and betamethasone, interrupted for onset of cataracts and increased intraocular pressure. We treated him with ophthalmic gel preparation containing a new recombinant form of manganese superoxide dismutase (rMnSOD) at a concentration of 12.5 µg/mL, only for the right eye, while left eye was treated with standard protocol of Bendazac-lysine g 0.5. Conclusion. This case report shows the protective effects of rMnSOD versus PSC disease, probably due to the capacity of rMnSOD of countering free radical species.

Study on the Protective Effect of a New Manganese Superoxide Dismutase on the Microvilli of Rabbit Eyes Exposed to UV Radiation.

We present a study on the protective effects against UV radiation of a gel formulation containing a new recombinant form of manganese superoxide dismutase on the conjunctiva and corneal epithelia of rabbit eyes. The integrity of the microvilli of both ocular tissues has been considered as an indicator of the health of the tissues. Samples, collected by impression cytology technique, were added of 80 µL of a gel formulation containing superoxide dismutase (2.0 µg/mL) and irradiated with UV rays for 30 minutes and were evaluated with scanning electron microscopy. Wilcoxon test was used to verify the possible occurrence of statistically significant differences between damage for treated and nontreated tissues. Application of gel produces a significant reduction of damage by UV irradiation of ocular epithelia; both epithelia present a significant reduction of damaged microvilli number if treated with the superoxide dismutase gel formulation: the p values (differences between damage found for treated and nontreated both ocular tissues) for conjunctiva and cornea samples were p ≪ 0.01 and p ≪ 0.0001, respectively, at confidence level of 95%. The administration of this gel formulation before UV exposure plays a considerable protective role in ocular tissues of rabbit eye with a significant reduction of the damage.

Dioxin-like PCB levels in maternal and umbilical cord sera of people living near dump sites in southern Italy: a pilot study of biomonitoring.

The "Triangle of Death" is an area of southern Italy highly polluted due to the presence of numerous illegal waste sites. To assess whether environmental contamination could produce an increased intake of harmful chemicals, we determined the serum levels of the 12 polychlorinated biphenyls (PCBs) indicated as "dioxin like" by the World Health Organization (WHO) in both maternal blood serum and umbilical cord blood serum of people residing in that area. The study was performed on 32 pregnant women and cord serum of their 32 newborn babies. Maternal serum concentrations ranged from 0.019 to 10.426 ng/mL (mean 1.590 ± 2.002 ng/mL), while umbilical serum concentrations ranged from 0.018 to 16.980 ng/mL (mean 1.858 ± 3.558 ng/mL). To normalize the toxic impact of the different congeners, the levels were expressed as WHO-TEQ, i.e., toxic equivalent concentrations. Total PCB concentrations (ΣPCBs WHO-TEQ 1998) were 0.297 TEQ-ng/mL in maternal serum and 0.663 TEQ-ng/mL in cord blood. These levels are significantly higher not only than those found in subjects resident in other areas but also in comparison to those reported in other published studies. This suggests that the exposure of both pregnant mothers and their fetuses to environmental pollution could produce a high intake of PCBs. The study may be important for the public health authorities to evaluate the level of exposure to environmental pollutants in human residents in the Triangle of Death.

Monitoring reversal of MET-mediated resistance to EGFR tyrosine kinase inhibitors in non-small cell lung cancer using 3'-deoxy-3'-[18F]-fluorothymidine positron emission tomography.

PURPOSE: MET amplification is one of the mechanisms underlying acquired resistance to EGFR tyrosine kinase inhibitors (TKI) in non-small cell lung cancer (NSCLC). Here, we tested whether 3'-deoxy-3'-[(18)F]-fluorothymidine ([(18)F]FLT) positron emission tomography/computerized tomography (PET/CT) can detect MET-mediated resistance to EGFR TKIs and monitor the effects of MET inhibitors in NSCLC. EXPERIMENTAL DESIGN: H1993 and H820 NSCLC cells with high and low levels of MET amplification, respectively, and HCC827-expressing MET, but without gene amplification, were tested for the effects of MET inhibitors on the EGFR pathway and proliferation both in vitro and in vivo. Nude mice bearing NSCLCs with and without MET amplification were subjected to [(18)F]FLT PET/CT before and after treatment with crizotinib or erlotinib (50 mg/kg and 100 mg/kg p.o. for 3 days). RESULTS: H1993 cells showed high responsiveness to MET inhibitors and were resistant to erlotinib. Conversely, HCC827 cells showed high sensitivity to erlotinib and were resistant to MET inhibitors. Accordingly, H1993 tumors bearing MET amplification showed a mean reduction in [(18)F]FLT uptake of 28% and 41% after low- and high-dose treatment with crizotinib for 3 days, whereas no posttherapy changes of [(18)F]FLT uptake were observed in HCC827 tumors lacking MET amplification. Furthermore, a persistently high [(18)F]FLT uptake was observed in H1993 tumors after treatment with erlotinib, whereas HCC827 tumors showed up to 39% reduction of [(18)F]FLT uptake following erlotinib treatment. Imaging findings were confirmed by Ki67 immunostaining of tumor sections. CONCLUSIONS: [(18)F]FLT PET/CT can detect MET-mediated resistance to EGFR TKIs and its reversal by MET inhibitors in NSCLC.

Enhancement of reaction conditions for the radiolabelling of DOTA-peptides with high activities of yttrium-90.

UNLABELLED: Peptide receptor radionuclide therapy (PRRT) has recently expanded due to radiolabelling of DOTA-peptides, such as the somatostatin analogues [DOTA(0), Tyr(3)]octreotate (DOTATATE). The achievement of high specific activities during procedures has been indicated as the critical factor to consent effective therapy. Several radiochemical factors may negatively impact reaction procedures such as pH, temperature and time of reaction. Our study was undertaken to explore the influence of radiochemical parameters, such as time of incubation, on reaction kinetics during the radiolabelling of DOTATATE with (90)Y. METHODS: Forty-five radiolabelling procedures were carried out using small volumes of yttrium-90, typically 60-78 µL. At nearly constant pH and temperature two different settings of radiolabelling procedures were implemented, removing the products from the heating water bath approximately after 30 min (group E, early; n=20) and after 39 min (group L, later; n=25). Quality controls were performed by means of both high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC). RESULTS: Reaction kinetics for (90)Y were found to a provide suitable percentage of incorporation at pH 4.5 for both groups. Reaction temperature was not different between groups E and L. A significant difference was found between the two groups in radiochemical yield, which was 95.6% ± 0.8 for group E and 98.2% ± 1.1 for group L (p<0.0001). The specific activity of the final product was 46.9 MBq/nmol. CONCLUSION: In order to achieve optimal specific activities, pH, temperature and time of reaction necessitate careful evaluation and setting. A statistically significant difference in labelling yield was found between a set of procedures completed at 39 min as compared to that executed at 30 min, keep the reaction pH and temperature constant.

Fully automated synthesis procedure of 4-[18F]fluorobenzaldehyde by commercial synthesizer: amino-oxi peptide labelling prosthetic group.

Automatic synthesis of 4-[18F]fluorobenzaldehyde has been developed by a commercially available TRACERlab FX(F-N) synthesis module to be used as prosthetic group for amino-oxy functionalized peptide labelling in clinical routine application. In addition a handmade purification device (HPD) has been setup to perform automatic cartridge purification as well as to back-up the reactor where one-pot synthesis is not applicable. Cartridges for solid phase extraction such as C18, C8, phenyl has been tested to best perform purification as well as activity recovery. Radiochemical yield (RCY) at end of synthesis (EOS) was in average 67% after about 45 min (90% decay corrected at EOB). The RCY of the entire procedure was 54% with a radiochemical purity above 99%.