Despite the attractiveness of breath analysis as a non-invasive means to retrieve relevant metabolic information, its introduction into routine clinical practice remains a challenge. Among all the different analytical techniques available to interrogate exhaled breath, secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS) offers a number of advantages (e.g., real-time, yet wide, metabolome coverage) that makes it ideal for untargeted and targeted studies. However, so far, SESI-HRMS has relied mostly on lab-built prototypes, making it difficult to standardize breath sampling and subsequent analysis, hence preventing further developments such as multi-center clinical studies. To address this issue, we present here a number of new developments. In particular, we have characterized a new SESI interface featuring real-time readout of critical exhalation parameters such as CO 2 , exhalation flow rate, and exhaled volume. Four healthy subjects provided breath specimens over a period of 1 month to characterize the stability of the SESI-HRMS system. A first assessment of the repeatability of the system using a gas standard revealed a coefficient of variation (CV) of 2.9%. Three classes of aldehydes, namely 4-hydroxy-2-alkenals, 2-alkenals and 4-hydroxy-2,6-alkedienals-hypothesized to be markers of oxidative stress-were chosen as representative metabolites of interest to evaluate the repeatability and reproducibility of this breath analysis analytical platform. Median and interquartile ranges (IQRs) of CVs for CO 2 , exhalation flow rate, and exhaled volume were 3.2% (1.5%), 3.1% (1.9%), and 5.0% (4.6%), respectively. Despite the high repeatability observed for these parameters, we observed a systematic decay in the signal during repeated measurements for the shorter fatty aldehydes, which eventually reached a steady state after three/four repeated exhalations. In contrast, longer fatty aldehydes showed a steady behavior, independent of the number of repeated exhalation maneuvers. We hypothesize that this highly molecule-specific and individual-independent behavior may be explained by the fact that shorter aldehydes (with higher estimated blood-to-air partition coefficients; approaching 100) mainly get exchanged in the airways of the respiratory system, whereas the longer aldehydes (with smaller estimated blood-to-air partition coefficients; approaching 10) are thought to exchange mostly in the alveoli. Exclusion of the first three exhalations from the analysis led to a median CV (IQR) of 6.7 % (5.5 %) for the said classes of aldehydes. We found that such intra-subject variability is in general much lower than inter-subject variability (median relative differences between subjects 48.2%), suggesting that the system is suitable to capture such differences. No batch effect due to sampling date was observed, overall suggesting that the intra-subject

Clozapine is the most widely used antipsychotic drug for the treatment of refractory schizophrenia. Here we report the case of two residual schizophrenic patients refractory to conventional antipsychotics who showed a poor response to atypical antipsychotics. The combination of risperidone and clozapine produced a noticeable improvement in the patients' clinical status and a shortening of the treatment response latency.

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Background and study aims Paris Classification is used to classify gastrointestinal superficial neoplastic lesions and to predict presence of submucosal invasion. We aimed to evaluate interobserver reliability and agreement for this classification among Western endoscopists. Methods A total of 54 superficial gastric lesions were independently classified according to Paris classification by eight endoscopists (4 experts and 4 non-experts). Observers were asked to classify two sets of images – first, obtained with high-resolution white light (HR-WL) endoscopy and secondly, with the same HR-WL images paired with images obtained with high-resolution Narrow Band Imaging (HR-NBI) – HR-WL + NBI image group. Results Overall interobserver reliability when asked to classify in I, II or III was good both using HR-WL images and HR-WL + NBI images (wK of 0.65 and 0.70, respectively). The proportion of agreement for type III lesions was 0.48 for HR-WL images increasing to 0.74 in the HR-WL + NBI group. Interobserver reliability for identification of a IIc component was only moderate (wK 0,47). NBI improves both sensitivity and interobserver reliability among trainees (from wK 0.19 to 0.47). Specificity was higher than sensitivity in predicting submucosal invasion. Conclusion Overall, the reliability of Paris classification is moderate to good. Training on this classification or its revision and use of technology such as NBI may improve not only reliability and agreement but also accuracy.

IntroductionEndoscopic submucosal dissection (ESD) is a minimally invasive organ-sparing endoscopic technique which allows en bloc resection of premalignant and early malignant lesions of the gastrointestinal tract regardless of size. In spite of the promising results, mainly from Japanese series, ESD is still not being widely used in western countries. This study aims to report the feasibility, safety and effectiveness of ESD technique for treating premalignant and early malignant gastrointestinal (GI) lesions (esophagus, gastric and rectum) in a Portuguese center.Patient and MethodsFrom December 2011 to November 2014, 34 GI lesions were treated by ESD. The location, en bloc and pathological complete resection (R0) rates, procedure time, complications and local recurrence were retrospectively evaluated.ResultsFrom 34 resected lesions, 18 were gastric (GL), 15 were rectal (RL) and one esophageal (EL). En bloc resection for each location was 17/18 (94%), 11/15 (73%) and 1/1 respectively. R0 was achieved in 16/18 (89%) GL, 9/15 (60%) RL and 1/1 EL. Mean resection time was 67 min for GL, 142 min for RL and 40 min for EL. Complications included immediate (6%) and delayed (3%) minor bleeding but no perforation. One local residual lesion from a RL was reported in the follow-up, effectively treated with an endoscopic technique. Disease-specific survival was 100% over a mean follow-up period of 14 months.ConclusionESD has shown to be a safe and feasible resection method, achieving high R0, low recurrence and complication rates. Our results are similar to those reported in other international series.