Transcatheter embolization with Squid, combined with other embolic agents or alone, in different abdominal diseases: a single-center experience in 30 patients

BACKGROUND: Squid, as Onyx, is an ethylene-vinyl alcohol copolymer (EVOH)-based liquid embolic agent developed for neuroradiologic interventions with poor application in abdominal district. Our aim was to evaluate safety, complications, and efficacy of transcatheter embolization using the two available formulations Squid-18 and 12, in 30 patients affected by different abdominal diseases.RESULTS: Transcatheter embolization with Squid, combined with other embolic agents, as poly vinyl alcohol (PVA) particles, coils and amplatzer plugs, or alone (type 2 endoleak), was performed in 30 patients, as follows: 10 portal vein embolizations (PVEs), 6 arteriovenous malformations (AVMs), 5 visceral artery aneurysms (VAAs), 4 type 2 endoleaks, 3 preoperative embolizations, 1 acute arterial bleeding, 1 female varicocele. Squid was always administered using dimethyl sulfoxide (DMSO) compatible microcatheters. Technical success, 30-day clinical success and complications were assessed. Technical success was 90%. 3 patients (2 AVMs, 1 VAA) required re-intervention successfully performed in all cases. Major complications, cases of microcatheter entrapment and DMSO-related poor pain control were not recorded. 30-day clinical success was 93.3%: in 2 patients submitted to PVE a sufficient future liver remnant (FLR) hypertrophy was not achieved.CONCLUSION: Squid was successfully used with low complication rate in many abdominal diseases showing a valid embolic action either combined with other embolic agents or alone in type 2 endoleak. The availability of different formulations (Squid-18 and Squid-12) variable for viscosity makes Squid preferable to Onyx as EVOH-based liquid embolic agent, even though comparable studies in different abdominal districts with a larger cohort of patients will be necessary

Biomarkers responses in fish (Atherinella brasiliensis) of paranaguá bay, southern Brazil, for assessment of pollutant effects

Paranaguá bay is a complex estuary located in southern Brazil containing three protected areas listed by UNESCO. Historically, the estuary has been affected by urban, industrial, agricultural and harbor activities, and occasional accidents. Specifically, the explosion of the Chilean ship Vicuña in December 2004 spilled methanol and crude and fuel oils which affected both protected and non-protected areas. The present study sought to investigate the pollution threat to aquatic organisms in order to evaluate the potential effects of pollutants. One hundred and twenty adult fish Atherinella brasiliensis were collected from different sites within Paranaguá estuary, including the harbor and open ocean, during summer, autumn and winter of 2005. Among the biomarkers, the somatic index, chemical analysis of bile, biochemical, genetic and morphological parameters were considered. Chemical analysis of bile showed a continuous bioavailability of polycyclic aromatic hydrocarbons (PAHs) according to proximity to the harbor site. The histopathological findings have demonstrated aconsiderable incidence of severe pathologies in the liver and gills, corroborated by biochemical disturbances and genetic damage. These findings indicate that more studies are necessary to evaluate both water quality and fish health so as to permit a better analysis of the impact of pollution in Paranaguá estuary.A Baia de Paranaguá é um complexo estuarino localizado no sul do Brasil constituído de três áreas de proteção ambiental listadas pela UNESCO. Historicamente, o estuário tem sido afetado por atividade urbana, industrial, agricultura e portuária, e eventualmente por acidentes. Particularmente a explosão do navio Chileno Vicuña em dezembro de 2004 derramou metanol, óleo cru e combustível atingindo áreas protegidas e não protegidas. O presente estudo tem por objetivo investigar a poluição em organismos aquáticos. Cento e vinte indivíduos adultos do peixe Atherinella brasiliensis foram coletados em quatro diferentes pontos de coleta no estuário de Paranaguá, partindo do porto até o oceano aberto nos períodos de verão, inverno e primavera de 2005. Os índices somáticos, parâmetros químicos, enzimáticos, genéticos e morfológicos foram considerados. As análises histopatológicas demonstraram expressiva incidência de patologia no fígado e nas brânquias algumas vezes corroboradas pelas alterações bioquímicas. Danos genéticos e anormalidades genéticas também foram observados. As análises químicas na bile mostraram uma contínua biodisponibilidade de hidrocarbonetos policíclicos aromáticos para os organismos aquáticos. Os dados obtidos indicam que a qualidade da água e a saúde dos peixes encontram-se bastante comprometidos no estuário de Paranaguá

An Exploratory Study of Field Failures

Field failures, that is, failures caused by faults that escape the testing phase leading to failures in the field, are unavoidable. Improving verification and validation activities before deployment can identify and timely remove many but not all faults, and users may still experience a number of annoying problems while using their software systems. This paper investigates the nature of field failures, to understand to what extent further improving in-house verification and validation activities can reduce the number of failures in the field, and frames the need of new approaches that operate in the field. We report the results of the analysis of the bug reports of five applications belonging to three different ecosystems, propose a taxonomy of field failures, and discuss the reasons why failures belonging to the identified classes cannot be detected at design time but shall be addressed at runtime. We observe that many faults (70%) are intrinsically hard to detect at design-time

Pharmacokinetic Interactions of Clinical Interest Between Direct Oral Anticoagulants and Antiepileptic Drugs

Direct oral anticoagulants (DOACs), namely apixaban, dabigatran, edoxaban, and rivaroxaban are being increasingly prescribed among the general population, as they are considered to be associated to lower bleeding risk than classical anticoagulants, and do not require coagulation monitoring. Likewise, DOACs are increasingly concomitantly prescribed in patients with epilepsy taking, therefore, antiepileptic drugs (AEDs), above all among the elderly. As a result, potential interactions may cause an increased risk of DOAC-related bleeding or a reduced antithrombotic efficacy. The objective of the present review is to describe the pharmacokinetic interactions between AEDs and DOACs of clinical relevance. We observed that there are only few clinical reports in which such interactions have been described in patients. More data are available on the pharmacokinetics of both drugs classes which allow speculating on their potential interactions. Older AEDs, acting on cytochrome P450 isoenzymes, and especially on CYP3A4, such as phenobarbital, phenytoin, and carbamazepine are more likely to significantly reduce the anticoagulant effect of DOACs (especially rivaroxaban, apixaban, and edoxaban). Newer AEDs not affecting significantly CYP or P-gp, such as lamotrigine, or pregabalin are not likely to affect DOACs efficacy. Zonisamide and lacosamide, which do not affect significantly CYP activity in vitro, might have a quite safe profile, even though their effects on P-gp are not well-known, yet. Levetiracetam exerts only a potential effect on P-gp activity, and thus it might be safe, as well. In conclusion, there are only few case reports and limited evidence on interactions between DOACs and AEDs in patients. However, the overall evidence suggests that the interaction between these drug classes might be of high clinical relevance and therefore further studies in larger patients' cohorts are warranted for the future in order to better clarify their pharmacokinetic and define the most appropriate clinical behavior

“Manos a la obra… Manos a la ciencia” Distintos Niveles educativos confluyen para investigar sobre infecciones virales respiratorias

Este proyecto extensionista tiene como objetivos vincular instituciones de distintos niveles educativos en torno a la investigación científica de infecciones virales respiratorias, y promover la actividad empírica y científica en el Laboratorio escolar. Los investigadores de la UNC y los docentes del secundario organizaron una conferencia con expertos, para padres y alumnos. Los docentes de primaria realizaron  la publicidad, promoción y comunicación de las actividades mediante afiches, y gestionaban los espacios y tiempos. La conferencia se llevó a cabo en junio, donde los expertos explicaron sobre el proceso salud-enfermedad referida a virus respiratorios. El circuito que recorre este proceso desde la visita al médico, la toma de muestra, su diagnóstico y tratamiento. En  agosto, en las aulas se impartieron las clases teóricas sobre el proceso de salud-enfermedad de las infecciones virales respiratorias, a los alumnos de  4º y 6º grados  del primario y a los de 5º año  del secundario. Los temas desarrollados fueron: bioseguridad, metodología de la investigación en salud, autocuidado, ciclos de infección, epidemiología haciendo hincapié en enfermedades respiratorias.  Los alumnos realizaron investigación bibliográfica y efectuaron análisis estadísticos. También visitaron laboratorios del Instituto de Virología. Además, se puso gran énfasis en recuperación de las actividades prácticas en el laboratorio del primario con el asesoramiento de los docentes e investigadores. En este punto se extrajeron muestras a los alumnos que participaron voluntariamente con el consentimiento firmado por sus padres. Este proyecto titulado “Manos a la Obra…Manos a la Ciencia” fue aprobado y subsidiado por el Ministerio de Ciencia y Tecnología de la Provincia de Córdoba (Mincyt), dentro del Programa “Innovaciones en el aula 2011”. Teniendo en cuenta que algunas de las actividades propuestas  están aún en desarrollo durante 2012, como completar la parte de materiales y métodos, contamos con algunos resultados que nos permiten elaborar conclusiones preliminares. Los resultados fueron un 4%  de detecciones de un tipo de virus respiratorio, aún cuando se consideró esta población escolar sana como control negativo. Reportándose entonces que esta infección respiratoria se presentó como un mini brote asintomático. Cabe aclarar que las detecciones virales  no fueron el fin buscado, sino la comprensión de todo el proceso de investigación que se lleva a cabo y del cual forman parte. Finalmente apostamos que desarrollar este tipo de proyectos es muy importante para promover la integración entre la Comunidad Educativa y la Científica, a través de actividades vinculadas con la investigación en salud.

Treatment of recurrent malignant gliomas with fotemustine monotherapy: impact of dose and correlation with MGMT promoter methylation

<p>Abstract</p> <p>Background</p> <p>In recurrent malignant gliomas (MGs), a high rate of haematological toxicity is observed with the use of fotemustine at the conventional schedule (100 mg/m²weekly for 3 consecutive weeks followed by triweekly administration after a 5-week rest period). Also, the impact of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status on fotemustine activity has never been explored in the clinical setting.</p> <p>Methods</p> <p>40 patients with recurrent pretreated MG were identified as being treated with fotemustine at doses ranging from 65 mg/m²to 100 mg/m². Patients were classified into 3 groups according to the dose of fotemustine received, from the lowest dosage received in group A, to the highest in group C. Analysis of MGMT promoter methylation in tumor tissue was successfully performed in 19 patients.</p> <p>Results</p> <p>Overall, 20% of patients responded to treatment, for a disease control rate (DCR, responses plus stabilizations) of 47.5%. Groups A and B experienced a response rate of 40% and 26.5% respectively, while the corresponding value for group C was 10%. Out of 19 patients, MGMT promoter was found methylated in 12 cases among which a DCR of 66.5% was observed. All 7 patients with unmethylated MGMT promoter were progressive to fotemustine.</p> <p>Conclusion</p> <p>Low-dose fotemustine at 65–75 mg/m²(induction phase) followed by 75–85 mg/m²(maintenance phase) has an activity comparable to that of the conventional schedule. By determination of the MGMT promoter methylation status patients might be identified who are more likely to benefit from fotemustine chemotherapy.</p

Brain metastases from solid tumors: disease outcome according to type of treatment and therapeutic resources of the treating center

<p>Abstract</p> <p>Background</p> <p>To evaluate the therapeutic strategies commonly employed in the clinic for the management of brain metastases (BMs) and to correlate disease outcome with type of treatment and therapeutic resources available at the treating center.</p> <p>Methods</p> <p>Four Cancer centres participated to the survey. Data were collected through a questionnaire filled in by one physician for each centre.</p> <p>Results</p> <p>Clinical data regarding 290 cancer patients with BMs from solid tumors were collected. Median age was 59 and 59% of patients had ≤ 3 brain metastases. A local approach (surgery and stereotactic radiosurgery) was adopted in 31% of patients. The local approach demonstrated to be superior in terms of survival compared to the regional/systemic approach (whole brain radiotherapy and chemotherapy, p = <.0001 for survival at 2 years). In the multivariate analysis local treatment was an independent prognostic factor for survival. When patients were divided into 2 groups whether they were treated in centers where local approaches were available or not (group A vs group B respectively, 58% of patients with ≤ 3 BMs in both cohorts), more patients in group A received local strategies although no difference in time to brain progression at 1 year was observed between the two groups of patients.</p> <p>Conclusions</p> <p>In clinical practice, local strategies should be integrated in the management of brain metastases. Proper selection of patients who are candidate to local treatments is of crucial importance.</p

Tissue factor as a potential coagulative/vascular marker in relapsing-remitting multiple sclerosis

ObjectivesRecent studies supported coagulation involvement in multiple sclerosis, an inflammatory-demyelinating and degenerative disease of the central nervous system. The main objectives of this observational study were to identify the most specific pro-coagulative/vascular factors for multiple sclerosis pathogenesis and to correlate them with brain hemodynamic abnormalities.MethodsWe compared i) serum/plasma levels of complement(C)/coagulation/vascular factors, viral/microbiological assays, fat-soluble vitamins and lymphocyte count among people with multiple sclerosis sampled in a clinical remission (n=30; 23F/7M, 40 ± 8.14 years) or a relapse (n=30; 24F/6M, age 41 ± 10.74 years) and age/sex-matched controls (n=30; 23F/7M, 40 ± 8.38 years); ii) brain hemodynamic metrics at dynamic susceptibility contrast-enhanced 3T-MRI during relapse and remission, and iii) laboratory data with MRI perfusion metrics and clinical features of people with multiple sclerosis. Two models by Partial Least Squares Discriminant Analysis were performed using two groups as input: (1) multiple sclerosis vs. controls, and (2) relapsing vs. remitting multiple sclerosis.ResultsCompared to controls, multiple sclerosis patients had a higher Body-Mass-Index, Protein-C and activated-C9; and a lower activated-C4. Levels of Tissue-Factor, Tie-2 and P-Selectin/CD62P were lower in relapse compared to remission and HC, whereas Angiopoietin-I was higher in relapsing vs. remitting multiple sclerosis. A lower number of total lymphocytes was found in relapsing multiple sclerosis vs. remitting multiple sclerosis and controls. Cerebral-Blood-Volume was lower in normal-appearing white matter and left caudatum while Cerebral-Blood-Flow was inferior in bilateral putamen in relapsing versus remitting multiple sclerosis. The mean-transit-time of gadolinium-enhancing lesions negatively correlated with Tissue-Factor. The top-5 discriminating variables for model (1) were: EBV-EBNA-1 IgG, Body-Mass-Index, Protein-C, activated-C4 and Tissue-Factor whereas for model (2) were: Tissue-Factor, Angiopoietin-I, MCHC, Vitamin A and T-CD3.ConclusionTissue-factor was one of the top-5 variables in the models discriminating either multiple sclerosis from controls or multiple sclerosis relapse from remission and correlated with mean-transit-time of gadolinium-enhancing lesions. Tissue-factor appears a promising pro-coagulative/vascular biomarker and a possible therapeutic target in relapsing-remitting multiple sclerosis.Clinical trial registrationClinicalTrials.gov, identifier NCT04380220