Effects of some endocrine disruptors on cell cycle progression and murine dendritic cell differentiation.

Endocrine disruptor chemicals (EDCs), which are predominantly present in the environment, are able to mimic or antagonise the biological activity of hormones primarily through the interaction with specific receptors. The main consequences are adverse effects on the growth and development of reproductive organs, the induction of cancer and effects on neuronal differentiation. In this study, we investigated the ability of certain EDCs, Bisphenol A (BPA), Bisphenol B (BPB), Bisphenol F (BPF), 4-n Nonylphenol (NP) and Octylphenol (OP), belonging to a homogeneous group of phenol origin, to interfere with specific cellular processes, namely, proliferation, by using MCF-7 breast carcinoma cells, and differentiation, by using murine bone marrow dendritic cells. We correlated the data on cell growth with the stimulation of cell cycle progression, which could become a step in the development of cancer, and we established a proliferation ranking between the tested EDCs: NP>BPA>OP>BPB>BPF. In addition, we investigated the ability of NP, BPA and OP to induce the differentiation of dendritic cells, the powerful antigen-presenting cells of the immune system. The differentiation and activation of these cells could affect a well-regulated immune response and determine an allergic sensitisation. We found that BPA and NP were active in determining differentiation.

Catheter salvage strategies in children with central venous catheter-related or -associated bloodstream infections: a systematic review and meta-analysis.

BACKGROUND: Optimal management of central venous catheter-related, or -associated, bloodstream infections (CRBSI or CLABSI) in children is not established. AIM: To evaluate success of catheter salvage strategies in paediatric patients. METHODS: Studies were retrieved from medical databases and article reference lists. Data were collected relating to clinical outcomes of two treatments: systemic antibiotics alone or in association with antimicrobial lock therapy (ALT). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from a mixed logistic effects model. Heterogeneity was summarized using I2 statistics. Publication bias was investigated by Egger's regression test and funnel plots. FINDINGS: From 345 identified publications, 19 met inclusion criteria (total of 914 attempted salvage strategies). To achieve successful catheter salvage, in CRBSI the addition of ALT was superior to systemic antibiotics alone (OR: -0.40; 95% CI: -1.41, 0.62): 77% (95% CI: 69, 85; I2 = 42.5%; P = 0.12) and 68% of success (95% CI: 59, 77; I2 = 0; P < 0.05), respectively. CRBSI recurrence was less common in studies that used ALT compared with systemic antibiotics alone: 5% (95% CI: 0, 13; I2 = 59.7%; P = 0.03) and 18% of recurrence (95% CI: 9, 28; I2 = 0; P < 0.05), respectively. Recurrences were low with both antibiotic locks and ethanol lock. No clear benefits of ALT addition compared to systemic antibiotic only were found in CLABSI (OR: -0.81; 95% CI: -0.80, 2.43). CONCLUSION: The addition of an antimicrobial lock solution to systemic antibiotic may be beneficial for successful catheter salvage in paediatric patients with CRBSI, depending on aetiology, whereas no statistically significant difference between systemic antibiotic with or without addition of an antimicrobial lock solution was found regarding CLABSI.

Thromboelastography clot strength profiles and effect of systemic anticoagulation in COVID-19 acute respiratory distress syndrome: a prospective, observational study.

OBJECTIVE: Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection may yield a hypercoagulable state with fibrinolysis impairment. We conducted a single-center observational study with the aim of analyzing the coagulation patterns of intensive care unit (ICU) COVID-19 patients with both standard laboratory and viscoelastic tests. The presence of coagulopathy at the onset of the infection and after seven days of systemic anticoagulant therapy was investigated. PATIENTS AND METHODS: Forty consecutive SARS-CoV-2 patients, admitted to the ICU of a University hospital in Italy between 29th February and 30th March 2020 were enrolled in the study, providing they fulfilled the acute respiratory distress syndrome criteria. They received full-dose anticoagulation, including Enoxaparin 0.5 mg·kg-1 subcutaneously twice a day, unfractionated Heparin 7500 units subcutaneously three times daily, or low-intensity Heparin infusion. Thromboelastographic (TEG) and laboratory parameters were measured at admission and after seven days. RESULTS: At baseline, patients showed elevated fibrinogen activity [rTEG-Ang 80.5° (78.7 to 81.5); TEG-ACT 78.5 sec (69.2 to 87.9)] and an increase in the maximum amplitude of clot strength [FF-MA 42.2 mm (30.9 to 49.2)]. No alterations in time of the enzymatic phase of coagulation [CKH-K and CKH-R, 1.1 min (0.85 to 1.3) and 6.6 min (5.2 to 7.5), respectively] were observed. Absent lysis of the clot at 30 minutes (LY30) was observed in all the studied population. Standard coagulation parameters were within the physiological range: [INR 1.09 (1.01 to 1.20), aPTT 34.5 sec (29.7 to 42.2), antithrombin 97.5% (89.5 to 115)]. However, plasma fibrinogen [512.5 mg·dl-1 (303.5 to 605)], and D-dimer levels [1752.5 ng·ml-1 (698.5 to 4434.5)], were persistently increased above the reference range. After seven days of full-dose anticoagulation, average TEG parameters were not different from baseline (rTEG-Ang p = 0.13, TEG-ACT p = 0.58, FF-MA p = 0.24, CK-R p = 0.19, CKH-R p  = 0.35), and a persistent increase in white blood cell count, platelet count and D-dimer was observed (white blood cell count p < 0.01, neutrophil count p = 0.02, lymphocyte count p < 0.01, platelet count p = 0.13 < 0.01, D-dimer levels p= 0.02). CONCLUSIONS: SARS-CoV-2 patients with acute respiratory distress syndrome show elevated fibrinogen activity, high D-dimer levels and maximum amplitude of clot strength. Platelet count, fibrinogen, and standard coagulation tests do not indicate a disseminated intravascular coagulation. At seven days, thromboelastographic abnormalities persist despite full-dose anticoagulation.