Additional neoadjuvant immunotherapy does not increase the risk of anastomotic leakage after esophagectomy for esophageal squamous cell carcinoma: a multicenter retrospective cohort study.

PURPOSE: Neoadjuvant chemoimmunotherapy (nICT) is a novel and promising therapy model for locally advanced esophageal squamous cell carcinoma.The objective of this study aimed to assessed the impact of additional neoadjuvant immunotherapy on patients' short-term outcomes, particularly the incidence of anastomotic leakage (AL) and pathological response. METHODS: Patients with locally advanced esophageal squamous cell carcinoma who received neoadjuvant chemotherapy (nCT)/ nICT combination with radical esophagectomy were enrolled from three medical centers in China. The authors used propensity score matching (PSM, ration:1:1, caliper=0.01) and inverse probability processing weighting (IPTW) to balance the baseline characteristics and compare the outcomes. Conditional logistic regression and weighted logistic regression analysis were used to further evaluate whether additional neoadjuvant immunotherapy would increase the risk of postoperative AL. RESULTS: A total of 331 patients getting partially advanced ESCC receiving nCT or nICT were enrolled from three medical centers in China. After PSM/IPTW, the baseline characteristics reached an equilibrium between the two groups. After matching, there were no significant difference in the AL incidence between the two groups ( P =0.68, after PSM; P =0.97 after IPTW), and the incidence of AL in the two groups was 15.85 versus 18.29%, and 14.79 versus 15.01%, respectively. After PSM/IPTW, both groups were similar in pleural effusion and pneumonia. After IPTW, the nICT group had a higher incidence of bleeding (3.36 vs. 0.30%, P =0.01), chylothorax (5.79 0.30%, P =0.001), and cardiac events (19.53 vs. 9.20%, P =0.04). recurrent laryngeal nerve palsy (7.85 vs. 0.54%, P =0.003). After PSM, both groups were similar in palsy of the recurrent laryngeal nerve (1.22 vs. 3.66%, P =0.31) and cardiac events (19.51 vs. 14.63%, P =0.41). Weighted logistic regression analysis showed that additional neoadjuvant immunotherapy was not responsible for AL (OR=0.56, 95% CI: [0.17, 1.71], after PSM; 0.74, 95% CI: [0.34,1.56], after IPTW). The nICT group had dramatically higher pCR in primary tumor than the nCT group ( P =0.003, PSM; P =0.005, IPTW), 9.76 versus 28.05% and 7.72 versus 21.17%, respectively. CONCLUSIONS: Additional neoadjuvant immunotherapy could benefit pathological reactions without increasing the risk of AL and pulmonary complications. The authors require further randomized controlled research to validate whether additional neoadjuvant immunotherapy would make a difference in other complications, and determine whether pathologic benefits could translate into prognostic benefits, which would require longer follow-up.

Accuracy improvement of determination of seven minor tobacco alkaloids in mainstream cigarette smoke using analyte protectants by gas chromatography-mass spectrometry.

Tobacco alkaloids are important precursors of carcinogenic tobacco-specific nitrosamines. Therefore, accurate quantification of tobacco alkaloids is highly important. This study investigates the compensation effects of novel analyte protectants (APs) for matrix effects (MEs) to determine seven minor tobacco alkaloids (nornicotine, myosmine, anabasine, anatabine, nicotyrine, 2,3'-bipyridine, and cotinine) in mainstream cigarette smoke with high accuracy and robustness. By comparing the heights and shapes of the chromatographic peaks before and after the addition of APs to standard solutions prepared in dichloromethane and cigarette smoke solutions, the compensation effects of 12 APs and their combinations on the MEs of seven minor tobacco alkaloids were evaluated, and the best combination of 2-pyridylethylamine (2 mg/mL)+1,2-decanediol (1 mg/mL) was identified. This AP combination could effectively improve the shapes and increase the heights (by 7-371%) of chromatographic peaks for standard solutions prepared in dichloromethane and cigarette smoke solutions. Before the addition of this AP combination, the slope ratios of the calibration curves for two types of standard solutions of the seven target chemicals were 71.4-159.8%, while they were 87.4-105.6% after the addition, indicating that this AP combination reduced the matrix difference between pure solvent and cigarette smoke solution. After adding the AP combination, the standard curves of solutions prepared in dichloromethane showed good linearity (r2 ≥ 0.999), the spiked recoveries were between 80.9% and 119.6%, and the inter- and intraday precisions were between 1.5-9.5% and 3.1-8.5%, respectively. Three commercial cigarette samples and one mixed standard solution were also tested under four different instrument working conditions to verify the long-term accuracy and ruggedness of the approach in routine real-world analysis of the method. The results showed that the RSD values were higher (3.5-25.4%) without the AP combination than that (<6.7%) with the AP combination. Because of its high accuracy, precision, and robustness, this method has good practical prospects.

Electromembrane extraction of nicotine in inhaled aerosols from tobacco cigarettes, electronic cigarettes, and heated tobacco products.

Heated tobacco products and electronic cigarettes are considered as alternatives to traditional tobacco cigarettes. However, it is crucial to monitor and compare the nicotine concentration in inhaled aerosols from these tobacco products, owing to the addictive nature and adverse effects of nicotine on human health. This study aimed to provide an electromembrane extraction (EME) combined liquid chromatography method to extract and determine nicotine in different inhaled aerosols. EME showed high extraction efficiency, selectivity, and sample clean-up capability. Under the optimal parameters, the linear range for nicotine was 0.1-200 mg L-1 (r2 > 0.9998), and the limit of detection was 0.02 mg L-1. Good precision was obtained with the intra- and inter-day relative standard deviations of 2.2 % and 2.8 %, respectively. Repeatability was satisfactory (<7.7 %), and recoveries ranged from 81.0 % to 112.8 %. Finally, this method has been successfully used for the determination and comparison of nicotine in aerosols from these three tobacco products.

Robust, comprehensive, sensitive analysis of flavour additives with carboxyl and hydroxyl groups in cigarette smoke combining silylation and gas chromatography-tandem mass spectrometry with an improved backflushing system.

Flavour additives with carboxyl and hydroxyl groups (FACHs), the key ingredients in characteristic flavours, are frequently detected in cigarette smoke. They are attracting increasing attention in regulating the flavour additives used in tobacco to curb youth tobacco use and prevent the use of additives that are harmful. In this study, a highly robust, sensitive, and precise method based on silylation and GC-MS/MS with an improved backflushing system was developed for the simultaneous analysis of 171 FACHs in cigarette smoke. Silylation has been shown to have advantages in terms of high selectivity and sensitivity to chemicals with carboxyl and hydroxyl groups, especially when combined with GC-MS/MS. The extraction and silylation conditions were optimised. Dichloromethane was used as the extraction agent. BSTFA in combination with 1% TMCS and 0.2% TMSI was selected as silylating agent for high silylation efficiency, particularly for hindered analytes. The method has been validated. The limit of detection (LOD) ranged from 0.6 to 332.3 ng/mL. 91.1% out of the analytes in QC samples had precisions lower than 10% during one month run. The improved backflushing system with a fused silica splitter was shown to be crucial in the excellent long-term robustness of the method. The developed method was used to determine flavour additives in 270 practical cigarette smoke samples with reliable results. A total of 154 FACHs were identified with wide-range levels among different cigarette brands.

Facile synthesis of magnetic sulfonated covalent organic framework composites for simultaneous dispersive solid-phase extraction and determination of ß-agonists and fluoroquinolones in food samples.

In this work, an efficient method for the determination of ß-agonists and fluoroquinolones was established, based on a mixed-mode sorbent of magnetic sulfonated covalent organic framework composites. By coupling with HPLC-MS/MS, the main factors that affect the extraction procedure were optimized. Under the optimal conditions, the proposed HPLC-MS/MS method was successfully utilized for the extraction of ß-agonists and fluoroquinolones in milk and pork meat samples. The method showed good linearities (R2 ≥ 0.9916), and low LOQs of 0.1-0.2 ng g-1 for ß-agonists and fluoroquinolones. The adsorption mechanism was investigated with the assistance of quantum chemistry calculation method, and it is worth noting that the sorbent relied mainly on the multiple adsorption mechanisms, including π-π stacking, hydrophobic, electrostatic attraction and hydrogen-bonding interactions. This work not only provides a simple method for the preparation of a mixed-mode sorbent, but also a routine analysis strategy for monitoring the illegal use of ß-agonists and fluoroquinolones.

Selective extraction and determination of aromatic amine metabolites in urine samples by using magnetic covalent framework nanocomposites and HPLC-MS/MS.

Purification and selective enrichment of ultra-low level metabolites in bio-samples is very important for HPLC-MS/MS analysis. A magnetic covalent organic framework (i.e. COFs) (TpPa-1) (i.e. 2,4,6-trihydroxybenzene-1,3,5-tricarbaldehyde-p-phenylenediamine) material was synthesized and used for a magnetic solid phase extraction (MSPE) method in aromatic amine (AA) metabolites (i.e. 1-naphthylamine, 2-naphthylamine, 3-aminobiphenyl and 4-aminobiphenyl) in urine, and then HPLC-MS/MS was employed for analysis. The morphology, pore structure, surface area, chemical composition, magnetic properties, and thermal stability of the synthesized magnetic COFs were characterized with several analysis techniques, such as nitrogen adsorption-desorption isotherms, HRTEM, FTIR, XRD, and so on. MSPE conditions were optimized and analytical performance of the developed method was characterized. The limit of detection (LOD) and limit of quantification (LOQ) of four AAs ranged from 0.01 to 0.07 ng mL-1 and 0.04 to 0.22 ng mL-1, respectively. The recoveries of 1-NA, 2-NA, 3-ABP, 4-ABP were in the range of 81.9-105%, 87.8-102%, 101-120%, 88.3-117%, respectively. Good intra-day and inter-day precision were obtained with RSD of less than 5.8% and 9.9%, respectively. Furthermore, the synthesized magnetic COFs absorbent could be recycled in MSPE at least 5 times. Analytical results of AA metabolites in real urine samples with the developed method showed significant difference (p < 0.01) between smokers and nonsmokers. Thus, urinary AA metabolites could be exposure biomarkers for cigarette smoke.

A highly efficient vortex-assisted liquid-liquid microextraction based on natural deep eutectic solvent for the determination of Sudan I in food samples.

A natural deep eutectic solvent (NADES) composed of choline chloride (ChCl) and sesamol was successfully employed in the vortex-assisted liquid-liquid microextraction (VALLME) of food toxicant Sudan I (1-phenylazo-2-naphthalenol) in food samples for HPLC-UV analysis. Sesamol-based NADESs exhibited better Sudan I extraction abilities than other deep eutectic solvents and conventional organic solvents. 1H NMR and 2D NOESY spectra were used to characterize the sesamol-based NADESs, indicating that hydrogen bonds were formed between ChCl and sesamol. The developed VALLME method showed a high extraction efficiency (near 100%) within 60 s at room temperature. Under the optimized extraction conditions, this established method showed good linearity (r 2 = 1.000) and a low limit of detection (LOD) of 0.02 mg kg-1. The recoveries were in the range of 93-118%, and the intra-day and inter-day precisions were less than 4.5%. The developed method was successfully applied to the determination of Sudan I in various food samples, including chili oil, chili sauce, and duck egg yolk. This method gave a higher recovery than that of the EU recommended method when applied to sample analysis.

Automatic time-shift alignment method for chromatographic data analysis.

Time shift among samples remains a significant challenge in data analysis, such as quality control of natural plant extracts and metabolic profiling analysis, because this phenomenon may lead to invalid conclusions. In this work, we propose a new time shift alignment method, namely, automatic time-shift alignment (ATSA), for complicated chromatographic data analysis. This technique comprised the following alignment stages: (1) automatic baseline correction and peak detection stage for providing useful chromatographic information; (2) preliminary alignment stage through adaptive segment partition to correct alignment for the entire chromatogram; and (3) precise alignment stage based on test chromatographic peak information to accurately align time shift. In ATSA, the chromatographic peak information of both reference and test samples can be completely employed for time-shift alignment to determine segment boundaries and avoid loss of information. ATSA was used to analyze a complicated chromatographic dataset. The obtained correlation coefficients among samples and data analysis efficiency indicated that the influences of time shift can be considerably reduced by ATSA; thus accurate conclusion could be obtained.

Characterization of cigarette smoke condensates by comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry (GC x GC/TOFMS). Part 2: basic fraction.

Cigarette smoke condensate is a complex chemical matrix. Analysis of nitrogen-containing compounds present therein is very difficult because of the limitation of the peak capacity of conventional one-dimensional chromatography. Extensive and laborious sample preparation is frequently required or selective detectors are frequently used. In this study, the basic fraction of mainstream cigarette smoke condensate has been investigated by using comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry (GC x GC/TOFMS). Auto data processing by TOFMS software combined with manual identification was used to assign the components. 377 nitrogen-containing compounds, including 155 pyridine derivatives, 104 quinoline/isoquinoine derivatives, and 56 pyrazine derivatives were tentatively identified. By selecting appropriate unique masses and in the light of the component positions in the structured chromatogram, alkyl-substituted pyridines, pyrazines, and quinolines/isoquinolines were separately shown and further validated. The peaks of eight individual positional isomers of two-carbon-substituted pyridines and thirteen positional isomers of methyl-substituted quinolines/isoquinolines were further confirmed, based on linear incremental retention behavior in combination with TOFMS and the structured chromatogram of GC x GC.

Characterization of complex hydrocarbons in cigarette smoke condensate by gas chromatography-mass spectrometry and comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry.

Gas chromatography-mass spectrometry with electron ionization and positive-ion chemical ionization and comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC x GC-TOF-MS) were applied for the characterization of the chemical composition of complex hydrocarbons in the non-polar neutral fraction of cigarette smoke condensates. Automated data processing by TOF-MS software combined with structured chromatograms and manual review of library hits were used to assign the components from GC x GC-TOF-MS analysis. The distributions of aliphatic hydrocarbons and aromatics were also investigated. Over 100 isoprenoid hydrocarbons were detected, including carotene degradation products, phytadiene isomers and carbocyclic diterpenoids. A total of 1800 hydrocarbons were tentatively identified, including aliphatic hydrocarbons, aromatics, and isoprenoid hydrocarbons. The identified hydrocarbons by GC x GC-TOF-MS were far more than those by GC-MS.

Analysis of cigarette smoke condensates by comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry I acidic fraction.

Cigarette smoke condensate is a complex chemical matrix, and analysis of its components is very difficult because of the limitation of the peak capacity and sensitivity of conventional chromatography and the extensive and laborious sample preparation that is frequently required. In this study, the acidic fraction of mainstream cigarette smoke condensate has been investigated by using comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry (GCxGC/TOFMS). Different column systems were tested and compared under proper GCxGC/TOFMS conditions. Auto data processing by TOFMS software combined with manual identification was used to assign the components. Over 1000 compounds, with S/N > or = 100, including 139 organic acids and over 150 phenols were tentatively identified by the developed method.