Clinical and therapeutic implications of epstein-barr virus in hiv-related lymphomas

Altres ajuts: Gilead Sciences (GLD19/00121)The incidence of lymphomas is increased in people living with HIV (PLWH). Aggressive B-cell non-Hodgkin lymphomas (NHLs) are the most common and are considered an AIDS-defining cancer (ADC). Although Hodgkin lymphoma (HL) is not considered an ADC, its incidence is also increased in PLWH. Among all HIV-related lymphomas (HRL), the prevalence of Epstein-Barr virus (EBV) is high. It has been shown that EBV is involved in different lymphomagenic mechanisms mediated by some of its proteins, contributing to the development of different lymphoma subtypes. Additionally, cooperation between both HIV and EBV can lead to the proliferation of aberrant B-cells, thereby being an additional lymphomagenic mechanism in EBV-associated HRL. Despite the close relationship between EBV and HRL, the impact of EBV on clinical aspects has not been extensively studied. These lymphomas are treated with the same therapeutic regimens as the general population in combination with cART. Nevertheless, new therapeutic strategies targeting EBV are promising for these lymphomas. In this article, the different types of HRL are extensively reviewed, focusing on the influence of EBV on the epidemiology, pathogenesis, clinical presentation, and pathological characteristics of each lymphoma subtype. Moreover, novel therapies targeting EBV and future strategies to treat HRL harboring EBV are discussed

Esquema quádruplo com furazolidona para retratamento do Helicobacter pylori, em pacientes ulcerosos

PURPOSE: Many of the currently used eradication regimens against Helicobacter pylori fail to cure the infection either due to antimicrobial resistance or to poor patient compliance. The infection leads to increased risk of developing potentially severe complications, such as gastric cancer. This study was aimed at assessing the efficacy and safety of a quadruple therapy with furazolidone for H. pylori retreatment. METHODS: Patients who had failed one or more eradication regimens against H. pylori infection underwent upper gastrointestinal endoscopy. Biopsy specimens were taken from the gastric antrum and corpus for histology and for a urease test and. Patients received omeprazole 20 mg, bismuth citrate 240 mg, tetracycline 500 mg, and furazolidone 200 mg, all twice daily for 7 days. Therapeutic success was evaluated by endoscopy and biopsies 8 weeks after the end of treatment. RESULTS: Sixty two patients were enrolled, and 58 completed the study. Under this protocol, H. pylori eradication was achieved in 39/58 patients (67%). Mild adverse events were reported. CONCLUSION: The short quadruple therapy course with furazolidone is well tolerated, inexpensive, and effective in retreatment for H. pylori infection. It is a good option for developing countries.OBJETIVO: Muitos dos esquemas atualmente usados na erradicação do Helicobacter pylori não conseguem curar a infecção, pela resistência bacteriana ou pela baixa adesão do paciente. Esta condição manterá os riscos de desenvolvimento das potenciais complicações graves da infecção. Este estudo procurou determinar a eficácia e segurança de um esquema quádruplo que associou a furazolidona para o retratamento da infecção pelo H. pylori. MÉTODOS: Pacientes que não alcançaram erradicação em um ou mais tratamentos foram submetidos à endoscopia digestiva alta e dois fragmentos do antro e do corpo foram retirados para exame histológico e de urease. Receberam então 20mg de omeprazol, 240mg de sub-citrato de bismuto, 500mg de tetraciclina e 200mg de furazolidona duas vezes ao dia por 7 dias. O sucesso terapêutico foi determinado pela negativação de nova biópsia endoscópica, após 8 semanas do tratamento. RESULTADOS: Sessenta e dois pacientes foram incluídos, cinqüenta e oito completaram o estudo. Por protocolo, 67% (39/58) dos pacientes conseguiram a erradicação da bactéria. Efeitos adversos leves foram relatados. CONCLUSÃO: O tratamento de curto prazo, em esquema quádruplo com a furazolidona , é bem tolerado, barato e eficaz no re-tratamento do H. pylori. Uma boa opção de re-tratamento para países em desenvolvimento

Variation of the Intercellular Space in the Esophageal Epithelium in Response to Hydrochloridric Acid Infusion in Patients with Erosive Esophagitis

The purpose of this study was to compare esophageal infusion with 0.1 N hydrochloridric acid (HCl) to esophageal infusion with saline in patients presenting with typical gastroesophageal reflux symptoms and erosive esophagitis. METHODS: Upper gastrointestinal endoscopy was performed on 44 prospective subjects, 29 of whom were included in the study. Eighteen patients presented with normal esophagi (Control Group "C"), nine of whom were infused with HCl and nine with saline. Eleven patients presented with erosive esophagitis (Lesion Group "L"), five of whom were infused with HCl and six with saline. Biopsies of the esophageal mucosa were collected before and after infusions. RESULTS: No statistically significant difference was found between the two types of infusions in terms of the dilation of the intercellular space of the esophageal epithelium, regardless of the status of the patient. CONCLUSIONS: Response to HCl infusion cannot be used as a marker for gastroesophageal reflux disease

Comorbidities are Frequent in Patients with Gastroesophageal Reflux Disease in a Tertiary Health Care Hospital

INTRODUCTION: Several aspects of gastroesophageal reflux disease (GERD) have been studied, but the frequency of comorbidities is not yet fully understood. OBJECTIVES: To study the prevalence of GERD comorbidities in a tertiary care hospital. METHODS: We prospectively studied 670 consecutive adult patients from the outpatient department of our facility. A diagnosis was established using clinical, endoscopic and/or pHmetry-related findings. Each patient's medical file was reviewed with respect to the presence of other medical conditions and diagnoses. RESULTS: Of the 670 patients, 459 (68.6%) were female, and the mean age was 55.94 (17-80 years). We registered 316 patients (47.1%) with the erosive form of GERD and 354 patients (52.9%) with the non-erosive form. A total of 1,664 instances of comorbidities were recorded in 586 patients (87.5%), with the most common being arterial hypertension (21%), hypercholesterolemia (9%), obesity (9%), type II diabetes mellitus (5%) and depression (4%). Two or more comorbidities were present in 437 individuals (64.8%). The occurrence of comorbidities increased with age and was higher in patients with the non-erosive form of GERD. CONCLUSIONS: In a tertiary referral population, comorbidities were very common, and these may have worsened the already impaired health-related quality of life of these patients. Clinicians caring for GERD patients in this setting must be aware of the likelihood and nature of comorbid disorders and their impact on disease presentation and patient management

Evaluación del comportamiento a macro-fisuración por fatiga de mezclas bituminosas modificadas con polvo de neumático

The use of crumb rubber modified bitumen (CRMB) in asphalt mixes is a road engineering technology that has become increasingly important in recent years. Given the many economic and environmental benefits of this type of binder, the goal is to give CRMB the same level of performance as conventional polymermodified bitumen. The appearance and propagation of cracks due to fatigue phenomena is one of the most common distresses affecting road pavements. Since crumb rubber enhances the mechanical properties of asphalt mixes, it can provide a viable solution for fatigue cracking. This paper presents the results of a comparative analysis of the fatigue-cracking behavior of asphalt mixtures manufactured with crumb rubber modified bitumen and polymer-modified bitumen.El empleo de betunes modificados con polvo de neumático usado en la fabricación de mezclas bituminosas es una de las técnicas que mayor auge está teniendo en los últimos años en la ingeniería de carreteras. Dadas sus grandes ventajas económicas y ambientales, este tipo de ligantes pretende conseguir prestaciones similares a la de los betunes modificados con polímeros utilizados habitualmente. La aparición de fisuras debido a fenómenos de fatiga es una de las patologías más comunes en firmes de carretera. Debido a las mejoras de las propiedades mecánicas del betún aportadas tras la incorporación de polvo de neumático, las mezclas fabricadas con estos ligantes se postulan como una posible solución a dicho problema. En este artículo se lleva a cabo un análisis comparativo del comportamiento a fisuración por fatiga realizado sobre mezclas bituminosas fabricadas con betún modificado con polvo de neumático y con polímeros.This research was carried out within the framework of the R + D + i project entitled Proyecto Integrado de Investigación, Desarrollo y Demostración de Tecnologías para la aplicación de neumáticos fuera de uso en firmes de carretera resistentes a la propagación de grietas (ref. IDI-20091076), funded by the Center for Industrial Technological Development (CDTI) of the Ministry of Science and Innovation in Spain

Efficacy of levofloxacin, amoxicillin and a proton pump inhibitor in the eradication of Helicobacter pylori in Brazilian patients with peptic ulcers

OBJECTIVES: The eradication of Helicobacter (H.) pylori allows peptic ulcers in patients infected with the bacteria to be cured. Treatment with the classic triple regimen (proton pump inhibitor, amoxicillin and clarithromycin) has shown decreased efficacy due to increased bacterial resistance to clarithromycin. In our country, the eradication rate by intention to treat with this regimen is 83%. In Brazil, a commercially available regimen for bacterial eradication that uses levofloxacin and amoxicillin with lansoprazole is available; however, its efficacy is not known. Considering that such a treatment may be an alternative to the classic regimen, we aimed to verify its efficacy in H. pylori eradication. METHODS: Patients with peptic ulcer disease infected with H. pylori who had not received prior treatment were treated with the following regimen: 30 mg lansoprazole bid, 1,000 mg amoxicillin bid and 500 mg levofloxacin, once a day for 7 days. RESULTS: A total of 66 patients were evaluated. The patients’ mean age was 52 years, and women comprised 55% of the sample. Duodenal ulcers were present in 50% of cases, and gastric ulcers were present in 30%. The eradication rate was 74% per protocol and 73% by intention to treat. Adverse effects were reported by 49 patients (74%) and were mild to moderate, with a prevalence of diarrhea complaints. CONCLUSIONS: Triple therapy comprising lansoprazole, amoxicillin and levofloxacin for 7 days for the eradication of H. pylori in Brazilian peptic ulcer patients showed a lower efficacy than that of the classic triple regimen

Association of a probiotic to a Helicobacter pylori eradication regimen does not increase efficacy or decreases the adverse effects of the treatment: a prospective, randomized, double-blind, placebo-controlled study

Abstract\ud \ud \ud \ud Background\ud \ud The treatment for the eradication of Helicobacter pylori (H. pylori) is complex; full effectiveness is rarely achieved and it has many adverse effects. In developing countries, increased resistance to antibiotics and its cost make eradication more difficult. Probiotics can reduce adverse effects and improve the infection treatment efficacy.\ud If the first-line therapy fails a second-line treatment using tetracycline, furazolidone and proton-pump inhibitors has been effective and low cost in Brazil; however it implies in a lot of adverse effects. The aim of this study was to minimize the adverse effects and increase the eradication rate applying the association of a probiotic compound to second-line therapy regimen.\ud \ud \ud \ud Methods\ud \ud Patients with peptic ulcer or functional dyspepsia infected by H. pylori were randomized to treatment with the furazolidone, tetracycline and lansoprazole regimen, twice a day for 7 days. In a double-blind study, patients received placebo or a probiotic compound (Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium bifidum and Streptococcus faecium) in capsules, twice a day for 30 days. A symptom questionnaire was administered in day zero, after completion of antibiotic therapy, after the probiotic use and eight weeks after the end of the treatment. Upper digestive endoscopy, histological assessment, rapid urease test and breath test were performed before and eight weeks after eradication treatment.\ud \ud \ud \ud Results\ud \ud One hundred and seven patients were enrolled: 21 men with active probiotic and 19 with placebo plus 34 women with active probiotic and 33 with placebo comprising a total of 55 patients with active probiotic and 52 with placebo. Fifty-one patients had peptic ulcer and 56 were diagnosed as functional dyspepsia. The per-protocol eradication rate with active probiotic was 89.8% and with placebo, 85.1% (p = 0.49); per intention to treat, 81.8% and 79.6%, respectively (p = 0.53). The rate of adverse effects at 7 days with the active probiotic was 59.3% and 71.2% with placebo (p = 0.20). At 30 days, it was 44.9% and 60.4%, respectively (p = 0.08).\ud \ud \ud \ud Conclusions\ud \ud The use of this probiotic compound compared to placebo in the proposed regimen in Brazilian patients with peptic ulcer or functional dyspepsia showed no significant difference in efficacy or adverse effects.\ud \ud \ud \ud Trial registration\ud \ud Current Controlled Trials ISRCTN04714018Drugs providing supported from Medley Indústria Farmacêutica, São Paulo, Brazil

Efficacy of a 7-day course of furazolidone, levofloxacin, and lansoprazole after failed Helicobacter pylori eradication

<p>Abstract</p> <p>Background</p> <p>Increasing resistance to clarithromycin and nitroimidazole is the main cause of failure in the <it>Helicobacter pylori </it>eradication. The ideal retreatment regimen remains unclear, especially in developing countries, where the infection presents high prevalence and resistance to antibiotics. The study aimed at determining the efficacy, compliance and adverse effects of a regimen that included furazolidone, levofloxacin and lansoprazole in patients with persistent <it>Helicobacter pylori </it>infection, who had failed to respond to at least one prior eradication treatment regimen.</p> <p>Methods</p> <p>This study included 48 patients with peptic ulcer disease. <it>Helicobacter pylori </it>infection was confirmed by a rapid urease test and histological examination of samples obtained from the antrum and corpus during endoscopy. The eradication therapy consisted of a 7-day twice daily oral administration of lansoprazole 30 mg, furazolidone 200 mg and levofloxacin 250 mg. Therapeutic success was confirmed by a negative rapid urease test, histological examination and 14C- urea breath test, performed 12 weeks after treatment completion. The Chi-square method was used for comparisons among eradication rates, previous treatments and previous furazolidone use.</p> <p>Results</p> <p>Only one of the 48 patients failed to take all medications, which was due to adverse effects (vomiting). Per-protocol and intention-to-treat eradication rates were 89% (95% CI- 89%–99%) and 88% (88–92%), respectively. Mild and moderate adverse effects were reported by 41 patients (85%). For patients with one previous treatment failure, the eradication rate was 100%. Compared to furazolidone-naïve patients, eradication rates were lower in those who had failed prior furazolidone-containing regimen(s) (74% vs. 100%, p = 0.002).</p> <p>Conclusion</p> <p>An empiric salvage-regimen including levofloxacin, furazolidone and lansoprazole is very effective in the eradication of <it>Helicobacter pylori</it>, particularly in patients that have failed one prior eradication therapy.</p

Short-term triple therapy with azithromycin for Helicobacter pylori eradication: Low cost, high compliance, but low efficacy

<p>Abstract</p> <p>Background</p> <p>The Brazilian consensus recommends a short-term treatment course with clarithromycin, amoxicillin and proton-pump inhibitor for the eradication of <it>Helicobacter pylori </it>(<it>H. pylori)</it>. This treatment course has good efficacy, but cannot be afforded by a large part of the population. Azithromycin, amoxicillin and omeprazole are subsidized, for several aims, by the Brazilian federal government. Therefore, a short-term treatment course that uses these drugs is a low-cost one, but its efficacy regarding the bacterium eradication is yet to be demonstrated. The study's purpose was to verify the efficacy of <it>H. pylori </it>eradication in infected patients who presented peptic ulcer disease, using the association of azithromycin, amoxicillin and omeprazole.</p> <p>Methods</p> <p>Sixty patients with peptic ulcer diagnosed by upper digestive endoscopy and <it>H. pylori </it>infection documented by rapid urease test, histological analysis and urea breath test were treated for six days with a combination of azithromycin 500 mg and omeprazole 20 mg, in a single daily dose, associated with amoxicillin 500 mg 3 times a day. The eradication control was carried out 12 weeks after the treatment by means of the same diagnostic tests. The eradication rates were calculated with 95% confidence interval.</p> <p>Results</p> <p>The eradication rate was 38% per intention to treat and 41% per protocol. Few adverse effects were observed and treatment compliance was high.</p> <p>Conclusion</p> <p>Despite its low cost and high compliance, the low eradication rate does not allow the recommendation of the triple therapy with azithromycin as an adequate treatment for <it>H. pylori </it>infection.</p

SiPMs coated with TPB : coating protocol and characterization for NEXT

Silicon photomultipliers (SiPM) are the photon detectors chosen for the tracking readout in NEXT, a neutrinoless {\beta}{\beta} decay experiment which uses a high pressure gaseous xenon time projection chamber (TPC). The reconstruction of event track and topology in this gaseous detector is a key handle for background rejection. Among the commercially available sensors that can be used for tracking, SiPMs offer important advantages, mainly high gain, ruggedness, cost-effectiveness and radio-purity. Their main drawback, however, is their non sensitivity in the emission spectrum of the xenon scintillation (peak at 175 nm). This is overcome by coating these sensors with the organic wavelength shifter tetraphenyl butadienne (TPB). In this paper we describe the protocol developed for coating the SiPMs with TPB and the measurements performed for characterizing the coatings as well as the performance of the coated sensors in the UV-VUV range.Comment: Submitted to the Journal of Instrumentation on december 26th 201