Primary cardiac T-cell lymphoma

Primary cardiac lymphoma (PCL), defined as a lymphoma clinically mimicking cardiac disease, with the bulk of the tumor located intrapericardially, is extremely rare in immunocompetent patients. Clinical manifestations vary depending on sites of involvement in the heart and include chest pain, arrhythmias, pericardial effusion, and heart failure. Diagnosis is often difficult and may require invasive procedures; in some cases, diagnosis is not made until autopsy. Histologically, nearly all cases of PCL reported thus far have been of B-cell origin. In this report, we describe a case of PCL of T-cell origin in an adult immunocompetent patient, the second reported in the literature to the best of our knowledge, and provide a brief overview of the features of previously published PCL cases.     

Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor

Histone deacetylases (HDACs) are a family of enzymes involved in the regulation of gene expression, DNA repair, and stress response. These processes often are altered in tumors, and HDAC inhibitors have had pronounced antitumor activity with promising results in clinical trials. Here, we report the crystal structure of human HDAC8 in complex with a hydroxamic acid inhibitor. Such a structure of a eukaryotic zinc-dependent HDAC has not be described previously. Similar to bacterial HDAC-like protein, HDAC8 folds in a single alpha/beta domain. The inhibitor and the zinc-binding sites are similar in both proteins. However, significant differences are observed in the length and structure of the loops surrounding the active site, including the presence of two potassium ions in HDAC8 structure, one of which interacts with key catalytic residues. CD data suggest a direct role of potassium in the fold stabilization of HDAC8. Knockdown of HDAC8 by RNA interference inhibits growth of human lung, colon, and cervical cancer cell lines, highlighting the importance of this HDAC subtype for tumor cell proliferation. Our findings open the way for the design and development of selective inhibitors of HDAC8 as possible antitumor agents.     

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.