Intraepithelial cells with irregular nuclear contours as a marker of esophagitis in children with gastroesophageal reflux disease

The diagnostic usefulness of intraepithelial cells with irregular nuclear contours (CINC) (squiggle cells) in esophageal endoscopic biopsies was investigated in 76 children (range age: 6 months-12 years) with gastroesophageal reflux disease. A further 20 subjects (range age: 10 months-11 years) served as controls. Based on the microscopic changes of the esophagus, according to traditional histological criteria, four groups of patients were identified: esophagitis was severe in 27, moderate in 20, mild in 21, and 8 patients had no clear-cut evidence of microscopic esophagitis. Data are given as mean±sd. Intraepithelial CINC had an immunohistochemical profile consistent with T lymphocytes. Patients with severe esophagitis had a CINC density (number per high-power field) (9.0±3.5) significantly higher than patients with mild esophagitis (7.0±3.0) and those without evidence of microscopic esophagitis (6.5±1.9) (P<0.05), but not different from those with moderate esophagitis (8.0±3.6); in all patient groups the CINC density was higher than in controls (2.2±0.3) (P<0.01). The percentage of reflux at 24-hr intraesophageal pH monitoring was higher in severe esophagitis patients (11.4±6.0) as compared to the other groups (moderate: 7.8±6.3; mild: 6.5±3.6; no microscopic esophagitis: 6.3±2.0;P<0.05). There was no correlation between CINC density and the amount of intraesophageal acid exposure in all patients. Furthermore, 27 of our patients had a normal intraesophageal acid exposure at the prolonged pH test (24-hr % of reflux 4.5): the CINC density was significantly higher in them than in the controls. We conclude that intraepithelial CINC in esophageal endoscopic biopsies from children with reflux disease represent a sensitive and early criterion of esophageal mucosa damage; they should be scanned in addition to the traditional histological parameters of acid-related esophageal inflammation.Presented in an abstract form at the 28th Annual Meeting of the European Society of Paediatric Gastroenterology and Nutrition, Jerusalem, May 28–June 1, 1995.     

Inhibition of platelet function by injectable isosorbide dinitrate

The possibility that isosorbide dinitrate (ISDN) inhibits platelet function in humans has been explored in vitro and in vivo. Incubation of citrated plateletrich plasma from healthy subjects with scalar concentrations (1.25, 12.5 and 125 μg/ml) of ISDN for 5 and 10 minutes resulted in a decrease in platelet aggregation after ADP, adrenaline, and arachidonic acid at the highest drug concentration (mean decrease: 72% [p < 0.01], 56% [p < 0.05] and 62% [p < 0.05], respectively, with the 10-minute incubation). Also, a significant reduction (30%) in generated thromboxane (TX)B₂ levels was observed after arachidonic acid (p < 0.01). ISDN was then infused at rate of 4 mg/hour for 30 minutes in 11 patients with angina and at a rate of 30 mg/hour for 20 minutes in 8. The smaller dose, which caused minor changes in arterial pressure and heart rate, was accompanied by a marked, significant decrease in ADP- and adrenaline-induced aggregation, with a nadir at 60 minutes from the infusion stop (decreases of 40% and 51% respectively). Circulating platelet aggregates also decreased, with a minimum (? 41%, p < 0.05) at the end of the infusion. The higher infusion rate, causing marked hemodynamic effects, was not accompanied by the occurrence of clear antiplatelet effects. Thus, ISDN can affect platelet function both in vitro and in vivo. The in vivo effect occurs at lower concentrations than in vitro but is blunted when a marked hemodynamic response occurs.     

Platelet‐rich plasma‐based bioactive membrane as a new advanced wound care tool

Chronic skin ulcers, consequence of diabetes and other pathological conditions, heavily compromise the patient life quality and represent a high and constantly growing cost for National Health Services. Autologous platelet‐rich plasma (PRP), has been proposed to treat these lesions. The absence of guidelines for the PRP production and the need of a fresh preparation for each treatment lead us to develop a protocol for the production of an allogenic PRP‐based bioactive membrane (BAM), standardized for platelet concentration and growth factor release. This work compares BAMs obtained starting from two different platelet concentrations. There was no direct correlation between the amount of growth factors released by BAM in vitro and the initial platelet count. However, different release kinetics were noticed for different growth factors, suggesting that they were differently retained by the two BAMs. The angiogenic potential of both BAMs was determined by Luminex Angiogenesis Assay. The biological activity of the factors released by the two BAMs was confirmed by cell proliferation and migration. A diabetic mouse chronic ulcer model was used to define the best PRP therapeutic dose in vivo. Both BAMs induced wound healing by increasing the thickness of the regenerated epidermis and the vessel number. However, a too high platelet concentration resulted in a slowdown of the membrane resorption that interfered with the skin healing. Overall, the results indicate that the BAMs could represent a natural and effective wound healing tool for the treatment of skin ulcers. Copyright © 2016 John Wiley & Sons, Ltd.     

Utility of risk scores to predict adverse events in cardiac lead extraction

Introduction: Increasing device implantations, patient comorbidities, and longer life expectancy contribute to an increased need for lead extraction. Even if transvenous lead extraction (TLE) is a highly successful procedure, some serious procedural complications are reported. In order to identify those patients who are at higher risk, risk stratification scores were proposed.

Areas covered: The major obstacles to lead extractions are represented by the body’s response to the foreign implanted material and by the following development of fibrotic reaction between the lead and the vascular system. Several clinical factors and device features are associated with major complications and worse outcomes. Although different multiparametric scores predicting the safety and the efficacy of TLE procedures were reported, none of these scores were prospective evaluated.

Expert commentary: A correct risk stratification is needed in order to refer complex patients to centers with proven experience and avoid futile procedures. Furthermore, the identification of high-risk patients allows to perform the extraction procedure in the operating room instead of electrophysiology lab. Albeit some risk scores able to predict adverse event in cardiac lead extraction were described, there are still several limitations to their use and reproducibility.     

Investigation on cobalt‐oxide nanoparticles cyto‐genotoxicity and inflammatory response in two types of respiratory cells

The increasing use of cobalt oxide (Co₃O₄) nanoparticles (NPs) in several applications and the suggested genotoxic potential of Co‐oxide highlight the importance of evaluating Co₃O₄ NPs toxicity. Cyto‐genotoxic and inflammatory effects induced by Co₃O₄ NPs were investigated in human alveolar (A549), and bronchial (BEAS‐2B) cells exposed to 1–40 µg ml^–1. The physicochemical properties of tested NPs were analysed by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Cytotoxicity was studied to analyze cell viability (WST1 test) and membrane damage (LDH assay), direct/oxidative DNA damage was assessed by the Formamido‐pyrimidine glycosylase (Fpg)‐modified comet assay and inflammation by interleukin (IL)‐6, IL‐8 and tumor necrosis factor‐alpha (TNF‐α) release (ELISA). In A549 cells, no cytotoxicity was found, whereas BEAS‐2B cells showed a viability reduction at 40 µg ml^–1 and early membrane damage at 1, 5 and 40 µg ml–1. In A549 cells, direct and oxidative DNA damage at 20 and 40 µg ml^–1 were detected without any effects on cytokine release. In BEAS‐2B cells, significant direct DNA damage at 40 µg ml^–1 and significant oxidative DNA damage with a peak at 5 µg ml^–1, that was associated with increased TNF‐α release at 1 µg ml^–1 after 2 h and increased IL‐8 release at 20 µg ml^–1 after 24 h, were detected. The findings show in the transformed alveolar cells no cytotoxicity and genotoxic/oxidative effects at 20 and 40 µg ml^–1. In normal bronchial cells, moderate cytotoxicity, direct DNA damage only at the highest concentration and significant oxidative‐inflammatory effects at lower concentrations were detected. The findings confirm the genotoxic‐oxidative potential of Co₃O₄ NPs and show greater sensitivity of BEAS‐2B cells to cytotoxic and oxidative‐inflammatory effects suggesting the use of different cell lines and multiple end‐points to elucidate Co₃O₄ NPs toxicity. Copyright © 2015 John Wiley & Sons, Ltd.     

Effects of colchicine on tissue factor in oxLDL-activated T-lymphocytes

Journal of Thrombosis and Thrombolysis - Several studies have shown that T-cells might be involved in pathophysiology of acute coronary syndromes (ACS). Tissue factor (TF) plays a key role in ACS....     

Neonatal seizures as onset of Inborn Errors of Metabolism (IEMs): from diagnosis to treatment. A systematic review

Metabolic Brain Disease - Neonatal seizures (NS) occur in the first 28&nbsp;days of life; they represent an important emergency that requires a rapid diagnostic work-up to start a prompt...     

Factors affecting long-term changes of liver stiffness in direct-acting anti-hepatitis C virus therapy: A multicentre prospective study

The long-term changes of liver stiffness (LS) in patients who achieve viral clearance after direct-acting anti-HCV therapy remain undefined. We conducted a multicentre prospective study to investigate this aspect. Patients with HCV infection treated with DAAs were enrolled from six Italian centres; they underwent clinical, biochemical, ultrasound and transient elastography evaluations before treatment (T0), 12 weeks (SVR12) and 24 months (T24) after the end of therapy. Among the 516 consecutive patients enrolled, 301 had cirrhosis. LS significantly decreased from T0 to SVR (14.3 vs 11.1 kPa, p = .002), with a progressive reduction until T24 (8.7 kPa, p < .001). However, only patients with steatosis and those who developed HCC did not experience a late improvement in LS. Multivariate analysis of baseline and follow-up variables identified steatosis as the only independent predictor of failure of LS improvement (OR 1.802, p = .013). ROC curve analysis of the association of LS with the risk of developing HCC showed that SVR12 ≥14.0 kPa had the highest accuracy (sensitivity 82%, specificity 99%; AUC: 0.774). Multivariate analysis revealed that LS was the only variable independently associated with an increased risk of developing HCC (OR 6.470, p = .035). Achieving an SVR was associated with a progressive, long-term decline of LS, suggesting a late improvement in liver fibrosis, besides the resolution of inflammation. Fatty liver and the development of HCC interfered with late reduction of LS. Patients with an LS ≥14 kPa at 12 weeks after the end of treatment were at higher risk for developing HCC.     

Systemic inflammatory diseases and silicone breast prostheses: report of a case of adult still disease and review of the literature

There has been a debate about the possibility of a link between silicone breast implants and the onset of systemic connective tissue diseases (eg, scleroderma, systemic lupus erythematosus, rheumatoid arthritis) and other inflammatory pathologies, such as silicone implant associated syndrome and adult Still disease. We report a case of adult Still disease in a patient with a silicone gel breast implant. The disease regressed with steroidal treatment, and the patient is now no longer steroid-dependent, although the implant is still in place.