Electrochemotherapy as palliative treatment in patients with advanced head and neck tumours: Outcome analysis in 93 patients treated in a single institution.

Abstract Purpose To describe outcomes of Electrochemotherapy as palliative treatment in patients with advanced head and neck (H&N) tumours. Methods Ninety-three patients (120 treatment sessions) with H&N recurrent and/or metastatic neoplasm were treated. Treatment response was assessed 4 weeks after ECT with clinical examination and two months after the first evaluation with a CT scan of the H&N for deep lesions evaluation. The grade of bleeding and pain before, at the end of treatment and one week after ECT were evaluated. Results Five percent of complete responses, 40% of partial responses were registered. Disease progression was seen in 20% of patients after the first ECT procedure, the remaining 34% of patients experienced stable disease. A good control of pain and bleeding was obtained, especially in patients with moderate symptoms before the treatment. No toxicities related to ECT were seen. Conclusions ECT is an interesting antitumoral therapy in advanced chemo and radio-refractory H&N neoplasms. ECT is able to reduce frequent symptoms, such as pain and bleeding, improving quality of life without damage to healthy tissue and with limited side effects. Moreover, ECT reduces hospitalization time and may contribute to an overall reduction in healthcare costs associated with advanced H&N cancers care

Platelet activation is associated with myocardial infarction in patients with pneumonia

BACKGROUND: Troponins may be elevated in patients with pneumonia, but associations with myocardial infarction (MI) and with platelet activation are still undefined.OBJECTIVES: The aim of this study was to investigate the relationship between troponin elevation and in vivo markers of platelet activation in the early phase of hospitalization of patients affected by community-acquired pneumonia.METHODS: A total of 278 consecutive patients hospitalized for community-acquired pneumonia, who were followed up until discharge, were included. At admission, platelet activation markers such as plasma soluble P-selectin, soluble CD40 ligand, and serum thromboxane B2 (TxB2) were measured. Serum high-sensitivity cardiac troponin T levels and electrocardiograms were obtained every 12 and 24 h, respectively.RESULTS: Among 144 patients with elevated high-sensitivity cardiac troponin T, 31 had signs of MI and 113 did not. Baseline plasma levels of soluble P-selectin and soluble CD40 ligand and serum TxB2 were significantly higher in patients who developed signs of MI. Logistic regression analysis showed plasma soluble CD40 ligand (p < 0.001) and soluble P-selectin (p < 0.001), serum TxB2 (p = 0.030), mean platelet volume (p = 0.037), Pneumonia Severity Index score (p = 0.030), and ejection fraction (p = 0.001) to be independent predictors of MI. There were no significant differences in MI rate between the 123 patients (45%) taking aspirin (100 mg/day) and those who were not aspirin treated (12% vs. 10%; p = 0.649). Aspirin-treated patients with MIs had higher serum TxB2 compared with those without MIs (p = 0.005).CONCLUSIONS: MI is an early complication of pneumonia and is associated with in vivo platelet activation and serum TxB2 overproduction; aspirin 100 mg/day seems insufficient to inhibit thromboxane biosynthesis. (MACCE in Hospitalized Patients With Community-acquired Pneumonia; NCT01773863)

Incidence and factors associated with the risk of sexually transmitted diseases in HIV-infected people seen for care in Italy: data from the Icona Foundation cohort.

Objectives: The aims of this study were to identify temporal trends in the incidence of sexually transmitted diseases (STDs) in a cohort of HIV-infected people and to evaluate factors associated with the risk of a new STD diagnosis. Methods: All HIV-infected patients in the Icona Foundation Study cohort enrolled after 1998 were included in this study. STD incidence rates (IRs) were calculated and stratified by calendar period. Predictors of STDs were identified using a Poisson regression model with sandwich estimates for standard errors. Results: Data for 9168 participants were analysed [median age 37.3 (range 18-81) years; 74% male; 30% men who have sex with men (MSM)]. Over 46 736 person-years of follow-up (PYFU), 996 episodes of STDs were observed [crude IR 21.3/1000 PYFU; 95% confidence interval (CI) 20.0-22.6/1000 PYFU]. In multivariable Poisson regression analysis, MSM [rate ratio (RR) 3.03; 95% CI 2.52-3.64 versus heterosexuals], calendar period (RR 1.67; 95% CI 1.42-1.97 for 2008-2012 versus 1998-2002), HIV RNA > 50 HIV-1 RNA copies/mL (RR 1.44; 95% CI 1.19-1.74 versus HIV RNA ≤ 50 copies/mL) and a current CD4 count < 100 cells/μL (RR 4.66; 95% CI 3.69-5.89; P < 0.001 versus CD4 count > 500 cells/μL) were associated with an increased risk of STDs. In contrast, older age (RR 0.82 per 10 years older; 95% CI 0.77-0.89) and being currently on ART (RR 0.38; 95% CI 0.33-0.45) compared with being ART-naïve or on a treatment interruption were associated with a lower risk of developing STDs. Conclusions: An increase in the incidence of STDs was observed in more recent years. Interventions to prevent STDs and potential spread of HIV should target the younger population, MSM and people currently not receiving ART

Observation of inverse Compton emission from a long γ-ray burst.

Long-duration γ-ray bursts (GRBs) originate from ultra-relativistic jets launched from the collapsing cores of dying massive stars. They are characterized by an initial phase of bright and highly variable radiation in the kiloelectronvolt-to-megaelectronvolt band, which is probably produced within the jet and lasts from milliseconds to minutes, known as the prompt emission1,2. Subsequently, the interaction of the jet with the surrounding medium generates shock waves that are responsible for the afterglow emission, which lasts from days to months and occurs over a broad energy range from the radio to the gigaelectronvolt bands1-6. The afterglow emission is generally well explained as synchrotron radiation emitted by electrons accelerated by the external shock7-9. Recently, intense long-lasting emission between 0.2 and 1 teraelectronvolts was observed from GRB 190114C10,11. Here we report multi-frequency observations of GRB 190114C, and study the evolution in time of the GRB emission across 17 orders of magnitude in energy, from 5 × 10-6 to 1012 electronvolts. We find that the broadband spectral energy distribution is double-peaked, with the teraelectronvolt emission constituting a distinct spectral component with power comparable to the synchrotron component. This component is associated with the afterglow and is satisfactorily explained by inverse Compton up-scattering of synchrotron photons by high-energy electrons. We find that the conditions required to account for the observed teraelectronvolt component are typical for GRBs, supporting the possibility that inverse Compton emission is commonly produced in GRBs

Insights into the high-energy γ-ray emission of Markarian 501 from extensive multifrequency observations in the Fermi era

We report on the γ-ray activity of the blazar Mrk 501 during the first 480 days of Fermi operation. We find that the average Large Area Telescope (LAT) γ-ray spectrum of Mrk 501 can be well described by a single power-law function with a photon index of 1.78 ± 0.03. While we observe relatively mild flux variations with the Fermi-LAT (within less than a factor of two), we detect remarkable spectral variability where the hardest observed spectral index within the LAT energy range is 1.52 ± 0.14, and the softest one is 2.51 ± 0.20. These unexpected spectral changes do not correlate with the measured flux variations above 0.3 GeV. In this paper, we also present the first results from the 4.5 month long multifrequency campaign (2009 March 15-August 1) on Mrk 501, which included the Very Long Baseline Array (VLBA), Swift, RXTE, MAGIC, and VERITAS, the F-GAMMA, GASP-WEBT, and other collaborations and instruments which provided excellent temporal and energy coverage of the source throughout the entire campaign. The extensive radio to TeV data set from this campaign provides us with the most detailed spectral energy distribution yet collected for this source during its relatively low activity. The average spectral energy distribution of Mrk 501 is well described by the standard one-zone synchrotron self-Compton (SSC) model. In the framework of this model, we find that the dominant emission region is characterized by a size ≲0.1 pc (comparable within a factor of few to the size of the partially resolved VLBA core at 15-43 GHz), and that the total jet power (≃1044 erg s-1) constitutes only a small fraction (∼10-3) of the Eddington luminosity. The energy distribution of the freshly accelerated radiating electrons required to fit the time-averaged data has a broken power-law form in the energy range 0.3 GeV-10 TeV, with spectral indices 2.2 and 2.7 below and above the break energy of 20 GeV. We argue that such a form is consistent with a scenario in which the bulk of the energy dissipation within the dominant emission zone of Mrk 501 is due to relativistic, proton-mediated shocks. We find that the ultrarelativistic electrons and mildly relativistic protons within the blazar zone, if comparable in number, are in approximate energy equipartition, with their energy dominating the jet magnetic field energy by about two orders of magnitude. © 2011. The American Astronomical Society

Non-AIDS defining cancers in the D:A:D Study-time trends and predictors of survival : a cohort study

BACKGROUND:Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.METHODS:Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.RESULTS:Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.CONCLUSIONS:The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC

Findenig Formation

The Findenig Formation consists of red to pink nodular centimetric thick beds of mudstone/wackestone, with interlayered millimetric to centimetric red marls, and, at places, some centimetric to decimetric calcarenitic (grainstone) intervals (allodapic layers) and breccia (calcirudite) beds in the upper part of the unit

Herpes simplex virus 2 causes apoptotic infection in monocytoid cells

Increasing evidence indicates that apoptosis can be associated with several viral infections, Here we demonstrate, that infection of monocytoid cells by Herpes simplex virus 2 (HSV-2) resulted, in time-and dose-dependent induction of apoptosis as an exclusive cytopathic effect, The phenomenon was confirmed using four different techniques, Conversely, apoptosis was not observed in the Vero cell line, Virus yield in monocytoid cells was delayed and reduced, although well detectable, in comparison with that observed in Vero cells, Nevertheless, released virions exhibited full infecting capability. Apoptosis induced by HSV-P was not inhibited by cycloheximide and only partially by an UV-treatment which completely abrogated infectivity. Virus-induced apoptosis was partly inhibited by indomethacin and was associated with a down-regulation of Bcl-2, A similar, but less pronounced, apoptosis-inducing effect in monocytoid cells was also observed with HSV-1 infection. Depending on the target cells, therefore, HSV could complete a cycle of infection which is characterized by apoptosis of infected cells