Cyanide, one of the most important toxic substances, has been found measurable with high sensitivity by capillary gas chromatography (GC) with cryogenic oven trapping upon injection of headspace (HS) vapor samples. The entire amount of cyanide in the HS sample could be cryogenically trapped prior to on-line GC analysis. A 0.5-mL volume of blood in the presence or absence of cyanide and propionitrile (internal standard, IS) was added to a vial containing 0.25 mL of distilled water, 0.3 g of Na2SO4, 0.2 mL of 50% H3PO4, and 0.1 g of ascorbic acid (when needed), and the mixture was heated at 70 °C for 15 min. A 5-mL volume of the HS vapor was introduced into a GC capillary column in the splitless mode at −30 °C oven temperature that was programmed up to 160 °C for GC analysis with nitrogen−phosphorus detection. A sharp peak was obtained for cyanide under the present conditions, and backgrounds were very clean. The extraction efficiencies of cyanide and IS were 2.89−3.22 (100 or 500 ng/mL) and 2.42%, respectively. The calibration curve showed good linearity in the range of 25−1000 ng/mL and the detection limit was ∼2 ng/mL. The coefficients of intraday and interday variations were 2.9 and 11.8%, respectively. The mean blood cyanide level measured for actual fire victims was 687 ± 597 ng/mL (mean ± SD, n = 9). Endogenous blood cyanide concentration for healthy subjects was 8.41 ± 3.09 ng/mL (mean ± SD, n = 6).
Despite the recommendations of the latest guidelines, the practical efficacy of universal screening for identifying Lynch syndrome (LS) among patients with colorectal cancer (CRC) may be limited in the real world due to infrequent referrals and the difficulties of genetic testing. Thus, the present study aimed to retrospectively analyze the results of universal screening of patients with CRC at a referral hospital in Japan. Immunohistochemistry was performed for mismatch repair proteins [including DNA mismatch repair protein MSH6 (MSH6), mismatch repair endonuclease PMS2 (PMS2), DNA mismatch repair protein Msh2 (MSH2) and DNA mismatch repair protein Mlh1 (MLH1)] and BRAF V600E mutation. Tumors that showed the following were considered to indicate LS and patients with such tumors were designated as genetic testing candidates (GTCs): i) Loss of MSH6/MSH2; ii) loss of MSH6 alone; iii) loss of PMS2 alone; and iv) loss of PMS2/MLH1 with negative BRAF V600E. MLH1 methylation and BRAF V600E mutation were analyzed in deficient mismatch repair (dMMR) tumors retrospectively. The frequency of dMMR and GTCs in an independent cohort of patients with young-onset CRC were also investigated. Universal screening revealed dMMR tumors, GTCs and LS probands in 7.3, 3.9 and 0.4%, respectively, of 463 patients with CRC. Although dMMR tumors were observed in both younger (<50 years) and older (≥60 years) patients, the GTCs were enriched in younger individuals. Evaluation of mismatch repair status in an independent cohort confirmed the high rate of GTCs in patients with young-onset CRC. The low detection rate of LS demonstrated in this study questions the implementation of routine universal screening in regions with low prevalence of LS. Considering the enrichment of GTCs in young-onset CRCs, age-restricted strategies may be simple and efficient practical alternatives to universal screening in the real world.
No specific biomarker for immune checkpoint inhibitor (ICI)-induced colitis has been established. Previously, we identified anti-integrin αvβ6 autoantibodies in >90% of patients with ulcerative colitis (UC). Given that a subset of ICI-induced colitis is similar to UC, we aimed to clarify the relationship between such autoantibodies and ICI-induced colitis.
Abstract Background and Aim Bright endoscopic light sources improve the visibility of the intestinal mucosa. A newly launched endoscopic system developed by Olympus Corporation (Tokyo, Japan) in 2020 required modification to prevent heat‐induced tissue damage, which reportedly occurs during magnifying chromoendoscopy. We investigated the mechanism of this phenomenon by evaluating the rise in temperature of stained and unstained porcine mucosa using the new and previous endoscopic systems. Methods Surface temperatures of stained (India ink, 0.05% crystal violet, 0.5% methylene blue, or 0.2% indigo carmine) and unstained porcine mucosa were evaluated using infrared imaging after contact with the new endoscopic system before it was modified (system‐EVIS X1; scope‐GIF‐EZ1500) and compared with a previous endoscopic system (system‐EVIS EXERAIII; scope‐GIF‐H190). We performed histological analysis of the porcine mucosa stained with 0.05% crystal violet after contact with the new endoscope to evaluate the degree of tissue damage. Results Surface temperatures remained < 40°C when the new endoscope was in contact with the unstained mucosa. However, the maximum surface temperature rose to > 70°C when the new endoscope was in contact with the stained mucosa (stained other than indigo carmine). Histological analysis revealed cavity formation in porcine epithelium stained with crystal violet where the endoscope made contact for . Using the previous endoscope, the maximum surface temperature of stained mucosa remained below approximately 60°C, and the surface temperature of the unstained mucosa remained below 30°C. Conclusions Heat transfer by light absorption could cause heat‐induced tissue damage during magnifying chromoendoscopy using the new endoscope.
<p>table S1 : recombination detection primers and qPCR primers. tableS2 : antibodies for immunohistochemistory and two chamber assay. tableS3 : list of PDAC patients</p>
