Ten-year follow-up of the largest oral Chagas disease outbreak. Laboratory biomarkers of infection as indicators of therapeutic failure.

Trypanosoma cruzi uses various mechanisms of infection to access humans. Since 1967, food contaminated with metacyclic trypomastigotes has triggered several outbreaks of acute infection of Chagas disease by oral transmission. Follow-up studies to assess the effectiveness of anti-parasitic treatment of oral outbreaks are rather scarce. Here, we report a 10-year laboratory follow-up using parasitological, serological, and molecular tests of 106 individuals infected in 2007 of the largest known outbreak of orally transmitted Chagas disease, which occurred in Caracas city, Venezuela. Before treatment (2007), specific IgA, IgM and IgG, were found in 71% (75/106), 90% (95/106) and 100% (106/106), respectively, in addition to 21% (9/43) parasitemia, Complement Mediated Lysis (CML) in 98% (104/106) and 79% (34/43) parasitic DNA for PCR. Blood culture detected parasitemia up to 18 months post-treatment in 6% (6/106) of the patients. In 2017, the original number of cases in the follow-up decreased by 46% and due to the country's economic situation, not all the trials could be carried out in the entire population. During follow-up, IgA and IgM disappeared promptly, with IgM persisting in 19% (20/104) of the patients three years after treatment. The anti-T. cruzi IgG remained positive 10 years later in 41% (20/49) of the individuals evaluated. CML remained positive seven years later in 79% (65/82) of the cases. PCR positive cases decreased after treatment but progressively recovered, being positive in 69% (32/46) of the individuals evaluated in 2017. The group of children (under 18 years of age) showed the highest PCR positivity with 76% (26/34) of the cases, but their parasitic load tended to diminish, while in adults the parasitic load regained their initial values. The simultaneous evaluation of serological tests and PCR of the patients allowed us to separate patients among responders and non-responders to the anti-parasitic treatment, and this information prompted us to apply a second anti-parasitic treatment in the group of non-responders. In this population not subjected to the like lihood of re-infection, adult patients were more likely to be non-responders when compared to children. These results suggest that rigorous laboratory follow-up with T. cruzi infectious biomarkers is essential to detect cases of parasite persistence.

Assessment of scattered radiation from hand-held dental x-ray equipment using the Monte Carlo method.

The objective of the present study was to evaluate the intensity and spatial distribution of the scattered radiation caused by the use of hand-held x-ray equipment in the zone occupied by the operator, using the Monte Carlo simulation for radiographic views of the upper and lower incisor teeth, and the consequent evaluation of the equivalent dose in the lens. In order to carry out this evaluation, the geometry of a typical dental facility with plaster walls containing the scattering object was used for the computational scenario implemented for the Monte Carlo method simulation. The PENELOPE code for Monte Carlo simulation of electron and photon transport was used with the radiation beam represented by a 60 kV spectrum, 1.5 mm Al and tungsten target. The simulations were carried out with typical parameters for workload and the number of radiographs/week. The results showed that the exposure levels varied significantly according to the angle of the x-ray beam and with the distance to the scattering object. It is concluded that the incorporation of hand-held equipment in dental radiology must be accompanied by the surveillance of occupational exposure levels and a review of the training structure of professionals in dental radiology regarding aspects of radiological protection and the particularities of using this type of equipment.

Monte Carlo Calculation of the Energy Spectrum of a 6 MeV Electron Beam using PENetration and Energy Loss of Positrons and Electrons Code.

BACKGROUND: The limited bibliographic existence of research works on the use of Monte Carlo simulation to determine the energy spectra of electron beams compared to the information available regarding photon beams is a scientific task that should be resolved. AIMS: In this work, Monte Carlo simulation was performed through the PENELOPE code of the Sinergy Elekta accelerator head to obtain the spectrum of a 6 MeV electron beam and its characteristic dosimetric parameters. MATERIALS AND METHODS: The central-axis energy spectrum and the percentage depth dose curve of a 6 MeV electron beam of an Elekta Synergy linear accelerator were obtained by using Monte Carlo PENELOPE code v2014. For this, the linear accelerator head geometry, electron applicators, and water phantom were simplified. Subsequently, the interaction process between the electron beam and head components was simulated in a time of 86.4x104 s. RESULTS: From this simulation, the energy spectrum at the linear accelerator exit window and the surface of the phantom was obtained, as well as the associated percentage depth dose curves. The validation of the Monte Carlo simulation was performed by comparing the simulated and the measured percentage depth dose curves via the gamma index criterion. Measured percentage depth- dose was determined by using a Markus electron ionization chamber, type T23343. Characteristic parameters of the beam related with the PDD curves such as the maximum dose depth (R100), 90% dose depth (R90), 90% dose depth or therapeutic range (R85), half dose depth (R50), practical range (Rp), maximum range (Rmax), surface dose (Ds), normalized dose gradient (G0) and photon contamination dose (Dx) were determined. Parameters related with the energy spectrum, namely, the most probable energy of electrons at the surface (Ep,0) and electron average energy (E- 0) were also determined. CONCLUSION: It was demonstrated that PENELOPE is an attractive and accurate tool for the obtaining of dosimetric parameters of a medical linear accelerator since it can reliably reproduce important clinical data such as the energy spectrum, depth dose, and dose profile.

Pyrosequencing versus methylation-specific PCR for assessment of MGMT methylation in tumor and blood samples of glioblastoma patients.

Circulating biomarkers in blood may provide an interesting alternative to risky tissue biopsies in the diagnosis and follow-up of glioblastoma patients. We have assessed MGMT methylation status in blood and tissue samples from unresected glioblastoma patients who had been included in the randomized GENOM-009 trial. Paired blood and tissue samples were assessed by methylation-specific PCR (MSP) and pyrosequencing (PYR). After establishing the minimum PYR cut-off that could yield a significant difference in overall survival, we assessed the sensitivity, specificity, positive predictive value and negative predictive value (NPV) of the analyses. Methylation could be detected in cfDNA by both MSP and PYR but with low concordance with results in tissue. Sensitivity was low for both methods (31% and 38%, respectively), while specificity was higher for MSP in blood than for PYR in plasma (96% vs 76%) and NPV was similar (56 vs 57%). Concordance of results in tissue by MSP and PYR was 84.3% (P < 0.001) and correlated with outcome. We conclude that detection of cfDNA in the blood of glioblastoma patients can be an alternative when tumor tissue is not available but methods for the detection of cfDNA in blood must improve before it can replace analysis in tumor tissue.

Cisplatin plus weekly CPT-11/docetaxel in advanced esophagogastric cancer: a phase I study with pharmacogenetic assessment of XPD, XRCC3 and UGT1A1 polymorphisms.

PURPOSE: A multicenter phase I trial to establish the recommended dose of CPT-11/docetaxel plus cisplatin in advanced esophagogastric cancer patients and to correlate the efficacy and toxicity with genetic polymorphisms in DNA repair genes (XPD and XRCC3) and the UGT1A1 gene. METHODS: Four dose levels with a fixed dose of cisplatin (60 mg/m(2)), day 1, and dose-escalation of CPT-11 (50-70 mg/m(2)) and docetaxel (25-30 mg/m(2)), days 1 and 8, every 3 weeks were planned. Polymorphisms of XPD (Asp312Asn and Lys751Gln), XRCC3 (Thr241Met) and UGT1A1*28 were examined in baseline peripheral blood. RESULTS: Twenty-eight patients were included at three different dose levels. Dose-limiting toxicities were febrile neutropenia and diarrhea; the recommended dose was established at CPT-11 60 mg/m(2) and docetaxel 25 mg/m(2) plus cisplatin 60 mg/m(2). Objective response was observed in 13 patients (50%). Median time to progression was 6.6 months, and median survival was 11.3 months. Median time to progression was 9.7 months for patients harboring the XRCC3 Met241Met genotype versus 8.4 months for patients with Thr241Met and 3.1 months for those with Thr241Thr (P = .04). CONCLUSIONS: CPT-11/docetaxel plus cisplatin is active in patients with advanced esophagogastric cancer. XRCC3 Met241Thr polymorphisms could be a useful marker to predict prognosis in patients treated with a cisplatin-based chemotherapy. However, these results are required to be confirmed with a great number of patients.

[Clinical assessment of Monolisa HCV Ag-Ab ULTRA (Bio-Rad) in a general hospital]. / Evaluación de la técnica Monolisa HCV Ag-Ab ULTRA (BioRad) en un hospital general.

INTRODUCTION: To evaluate a new test based on simultaneous detection of HCV antibodies and antigen (Monolisa HCV Ag/Ab ULTRA; Bio-Rad, Marnes la Coquette, France). METHODS: We studied samples from two groups of patients and 7 commercial HCV seroconversion panels (75 samples). Group 1: 1360 serum samples from patients referred for routine testing of anti HCV antibodies. Group 2: 333 serum samples from 183 hemodialysis patients. All samples were tested by the Ortho HCV 3.0 technique (Ortho-Clinical Diagnostics, Amersham, UK) and the Monolisa HCV Ag-Ab ULTRA technique. RESULTS: Group 1: Seventy-four of 1360 serum samples were positive by Ortho HCV and 77 by Monolisa. In 1353 samples, the results with the two tests were concordant: 1281 negative and 72 positive. Five samples were positive only by Monolisa and 2 only by Ortho (overall agreement: 99.5%). Group 2: Results were concordant in 325 samples, 308 negative and 17 positive. Seven samples were positive by Monolisa and negative by Ortho. The sensitivity of the Monolisa test in hemodialysis patients was clearly higher than that of the Ortho test (100% and 70.8%, respectively). Monolisa detected HCV infection in 43 of 75 samples from the seroconversion panels; only 18 positive samples were detected by Ortho HCV. Monolisa reduced the window period by up to 72 days. CONCLUSIONS: Our data indicate high agreement between the Monolisa and Ortho tests in samples from the general population. In hemodialysis patients, however, Monolisa was more sensitive. In addition, the Monolisa test significantly reduced the window period of HCV infection.