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Background: Approximately one in five cancer patients use proton pump inhibitors (PPIs). In this work, we studied the effect of PPI co-medication during neoadjuvant chemoradiotherapy (NCRT) for locally advanced rectal cancer (LARC) based on the phase III PRODIGE 23 trial. Materials and methods: We gathered data on PPI exposure for patients from the PRODIGE 23 trial. PPI exposure was defined as PPI use during capecitabine treatment, either during CRT or as adjuvant therapy. The oncological outcomes included recurrence-free survival (RFS), overall survival (OS), cumulative incidence of metastatic recurrence, and pathological response to preoperative treatment. The association of PPI use with RFS, metastatic recurrence, and histological complete response was evaluated using univariate and multivariate Cox models. Results: We analyzed data from 332 patients [165 in the NAC group with mFOLFIRINOX, capecitabine-based (CAP50) CRT, and surgery, and 167 in the standard-of-care control arm with CAP50 CRT and surgery]. Thirty-eight patients were co-administered a PPI during capecitabine administration. After a median follow-up of 49.4 months, the 3-year RFS rates were 74.1% [95% confidence interval (CI) 68.6% to 78.8%] and 68.4% (95% CI 51.2% to 80.7%) in the non-PPI and PPI groups, respectively, with no significant differences (P = 0.16). The 3-year OS rates were 91.2% (95% CI 87.2% to 93.9%) and 83% (95% CI 65.7% to 92%) in the non-PPI group and PPI groups, respectively, with no significant differences (P = 0.38). We observed no difference in the pathological complete response rate between both groups. Conclusions: We observed no significant association between PPI exposure and survival or pathological response of patients receiving capecitabine-based CRT for LARC, supporting earlier research findings.

The enzyme lecithin:cholesterol acyl transferase has been measured both in total plasma and in the fraction of plasma from which very low and low density lipoproteins have been removed by ultracentrifugation. The correlation between the activity of the enzyme and the free cholesterol concentration was positive in whole plasma and negative in apoB-deficient plasma. On the other hand, the positive correlation between plasma triglycerides and cholesterol esterification was not changed by the removal of apoB-containing lipoproteins. Subjects with the highest levels of high density lipoprotein cholesterol were found to have the lowest enzyme activity, but this correlation was disclosed only in apoB-deficient plasma. This inverse relationship was abolished when the enzyme activity was measured in the absence of all lipoproteins with a density less than 1.125 g/ml. Cholesterol esterification, when determined after removal of lipoproteins with a density less than 1.063 g/ml, was negatively correlated with the in vivo plasma concentration of lipoproteins in the density range 1.063-1.125 g/ml. The same results were obtained in vitro by addition of increasing amounts of this class of high density lipoproteins either in total plasma or in the ultracentrifuged fractions of plasma. This provides further evidence that the lighter density class of high density lipoproteins inhibits the enzyme reaction under physiological conditions.

The occurrence of bone fractures is frequent in the elderly population, and in cancer patients, especially with bone metastases. The growing incidence of cancer associated with an aging population implies important health challenges, including bone health. Decisions on cancer care in older adults have to take into account older adults' specificities. Screening tools as G8 or VES 13 and evaluating tools as comprehensive geriatric assessment (CGA) do not include bone-related items. Bone risk assessment is indicated according to identification of geriatric syndromes such as falls, history, and the oncology treatment plan. Some cancer treatments disrupt bone turnover and decrease bone mineral density. This is mainly caused by hypogonadism, induced by hormonal treatments and some chemotherapies. Treatments can also cause direct (i.e., chemotherapy, radiotherapy or glucocorticoids) or indirect toxicity through electrolyte disorders (i.e., some chemotherapies or tyrosine kinase inhibitors) on bone turnover. Bone risk prevention is multidisciplinary. Certain interventions proposed in the CGA aim to improve bone health and reduce the risk of falling. It is also based on the drug management of osteoporosis, and the prevention of complications from bone metastases. Management of fractures, related or not to bone metastases relates to the concept of orthogeriatrics. It is also based on the benefit-risk ratio of the operation, access to minimally invasive techniques, prehabilitation or rehabilitation, but also the prognosis related to cancer and geriatric syndromes. Bone health is essential in older cancer patient's care. Bone risk assessment should be part of CGA in routine use and specific decision-making tools should be developed. Bone event management must be integrated throughout the patient's care pathway and oncogeriatrics multidisciplinarity should include rheumatological expertise., (Copyright © 2023 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Purpose: Proton pump inhibitors (PPIs) are one of the most widely used drugs worldwide and are involved in several drug interactions. Recently, several studies have suggested that PPIs may interfere with the efficacy of capecitabine. This study primarily aimed to investigate the effects of PPI intake on the pathologic response rate of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy with capecitabine., Method: A retrospective study was conducted at a French Comprehensive Cancer Center. Patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by surgery were included in the study. Demographic parameters, treatment characteristics, survival data, and PPI intake data were collected. Frequencies and percentages were reported for categorical variables and medians and interquartile ranges for continuous variables. Distribution of variables was compared according to PPI treatment using the chi-square test or Fisher's exact test for categorical data and nonparametric Wilcoxon tests for continuous variables. Survival data were estimated using the Kaplan-Meier method and compared using the log-rank test., Results: In total, 215 patients were included, of whom 135 (62.8%) were men. The PPI intake frequency was 16.1%. The rate of complete pathological response was not significantly lower in patients on PPIs than in those not on PPIs (8.7% vs. 19%, p = 0.36). PPI intake was not associated with a statistically significant decrease in recurrence-free survival (hazard ratio [HR] = 1.26, 95% confidence interval [CI] 0.61-2.60, p = 0.54) or overall survival (HR = 0.95, 95% CI 0.33-2.76, p = 0.93)., Conclusion: No significant association was observed between PPI co-medication and complete pathological response or survival in patients treated for locally advanced rectal cancer. However, the safety of PPIs could not be confirmed. Further ancillary studies of prospective clinical trials or studies using the Health Data Hub are necessary to explore the effects of PPIs on rectal cancer more accurately., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Proton pump inhibitors (PPIs) are one of the most widely used drugs worldwide and are overprescribed in patients with cancer; there is increasing evidence of their effects on cancer development and survival. The objective of this narrative review is to comprehensively identify cancer medications that have clinically meaningful drug-drug interactions (DDIs) with PPIs, including loss of efficacy or adverse effects, and to explore the association between PPIs and cancer. Methods: A PubMed search of English language studies published from 1 January 2016, to 1 June 2021 was conducted. The search terms included "proton pump inhibitors," "cancer," "chemotherapy," "immunotherapy," "hormonotherapies," "targeted therapies," "tyrosine kinase inhibitors," and "gut microbiome". Recent and relevant clinical trials, meta-analyses, and reviews were included. Results: PPIs may have pro-tumor activity by increasing plasma gastrin levels or anti-tumor activity by inhibiting V-ATPases. However, their impact on cancer survival remains unclear. PPIs may decrease the efficacy of some antineoplastic agents through direct DDIs (e.g., some tyrosine kinase inhibitors, capecitabine, irinotecan, methotrexate). More complex DDIs seem to exist for immunotherapies with indirect interactions through the microbiome. PPIs worsen hypomagnesemia, bone loss, iron, and vitamin B12 deficiencies but may have a protective effect on the renal system. Discussion/Conclusions: PPIs may interact with the cancer microbiome and the efficacy of various antineoplastic agents, although only a few DDIs involving PPIs are clinically significant. Further pharmaco-epidemiological studies are warranted, but physicians should be aware of the potential consequences of PPI use, which should be dose appropriate and prescribed according to guidelines., Competing Interests: AT has served in a consulting/advisory role and/or received honoraria from Amgen, Merck, Servier, Mylan, and has received travel, accommodations, and expenses from Pfizer, Sanofi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bridoux, Simon and Turpin.)

High resolution mass spectrometry (HRMS) can resolve thousands of compounds in complex mixtures such as natural organic matter. However, HRMS is seldom sufficient to fully resolve the molecular heterogeneity of Humus in the soil matrix, especially if no preliminary simplification of Humus complexity is applied and if a single ionization technique is used. Here we show that HRMS, when applied with both photoionization (APPI) and electrospray ionization (ESI) and combined with the extensive molecular simplification provided by a humeomic fractionation, significantly increases identification of the molecular composition of soil Humus. Different sequential extractions separate the soil Humeome in three organosoluble fractions (ORG1-3) and two hydrosoluble fractions (AQU2 and RESOM), which showed distinct molecular characteristics. The ORG fractions were particularly homogeneous and rich in alkyl compounds including unsaturated hydrocarbons and lipid compounds found mainly in ORG 1 and ORG 3, but also aromatic compounds comprising lignin-like molecules and condensed structures mainly detected in ORG2. The AQU2 fractions revealed greater complexity and heterogeneity due to the simultaneous detection of sugars, amino sugars, tannins and N-containing compounds not detectable in appreciable concentrations in other fractions. The most recalcitrant RESOM fraction contained highly reduced molecules and condensed structures. The combined use of APPI and ESI showed a marked selectivity in the detection of chemically different molecules separated in each fraction, thereby enhancing their molecular characterization. Specifically, APPI tended to ionize less oxidized and N-containing molecules, and compounds with high concentrations of unsaturation or aromatics, while ESI was more prone to detect highly oxidized compounds consisting of large O/C ratios. Our findings indicate that the combination of a soil Humeome fractionation with a detailed high resolution characterization of differently ionized molecules in the separated fractions enables a far deeper understanding of the molecular composition of soil Humus and the comprehension of its environmental reactivity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A Humeomic fractionation revealed the humus molecular composition of two uncropped calcareous soils of Northern France and differentiated the soils Humeome by extracting humic components first unbound to the organo-mineral matrix and then liberated from their progressively stronger intermolecular and intramolecular ester and ether linkages. We separated organo- (ORG1-3) and water-soluble (AQU2 and AQU4) fractions, a final extractable fraction (RESOM) and soil residues. Organo-soluble fractions were studied by GC coupled with high-resolution mass spectrometry (GC/qTOF-MS), all fractions underwent mono- and two-dimensional liquid-state NMR (except for the iron-rich AQU4 fraction), while solid-state 13 C-CPMAS-NMR spectroscopy analyzed soil residues. The Calcaric Leptosol (A) showed a larger mass extraction than the Calcaric Cambisol (B), and a greater cumulative C and N content in its Humeome. Both soils showed the greatest weight yield for AQU4 fraction, followed by ORG2, RESOM, ORG1, AQU2, and ORG3. ORG2 was the most differentiating fraction between the two soils for both compound concentration and diversity, showing a larger C content for soil A than for soil B and a different distribution in aromatic compounds, fatty acids, and dicarboxylic acids. No significant differences between soils were found for ORG 3, suggesting similar processes of OM stabilization for its recalcitrant components, mostly hydrophobic esters of alkanoic, hydroxy, and aromatic acids with linear alkanols. We confirmed that Humeomic fractionation coupled to advanced analytical instrumentations enabled a detailed molecular characterization of the soil Humeome and differentiated between the two calcareous grassland soils and the other soils previously subjected to Humeomics., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Three methods of membrane separation by dead-end, tangential, and centrifugal ultrafiltration (UF) were considered in order to understand the physicochemical phenomena occurring during the preconcentration of the colloidal phase of soil water. The analytical approach used involved dynamic light scattering (DLS), transmission electron microscopy (TEM), determination of total organic carbon (TOC-metry) and mass spectrometry (ICP-MS). The mass amounts of the major components of the colloidal phase, i.e. Al, Fe and total organic carbon (TOC), as well as the mass amount of uranium considered as a trace element of environmental interest, were determined, both in soil water, and in the concentrates (i.e. retentates) and filtrates of this water obtained by the 3 methods tested. Dead-end ultrafiltration led to an enlargement of the size distribution towards larger sizes because of agglomeration/aggregation phenomena. This method also generated enrichment of concentrates, in particular in organic matter. The consequence was that large structures were observed coating or embedding the particles initially present individually dispersed in the test sample. The mass amounts of elements and TOC increased more importantly than expected, which confirmed the enrichment of the concentrates from the dissolved phase probably by sorption on colloidal objects. To a lesser extent similar effects were observed after tangential ultrafiltration. Such phenomena were not observed after centrifugal ultrafiltration. From a practical point of view, both tangential and centrifugal ultrafiltration proved to be both the most practical and the best suited for the preconcentration of soil water sample. Finally, centrifugal ultrafiltration has proved to be the best compromise given the preservation of colloidal particles and method practicality., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The molecular composition of soil organic matter (SOM) of two calcareous soils highly rich in carbonates was assessed before and after decarbonation by acid washing with HCl through 13 C-CPMAS-NMR spectroscopy and off-line thermochemolysis coupled with gas chromatography and mass spectrometry (THM-GC-MS). The acidic treatment promoted a considerable concentration of organic matter in both soils, thus improving the identification of molecules otherwise not easily detectable. Decarbonation induced only a slight loss of soil organic carbon (SOC), corresponding to 1.4 and 2.7% for A and B soils respectively. The acidic treatment also led to an increase in the organic carbon/total nitrogen (OC/N) ratio in soil A, while an opposite variation was found for the second soil. Moreover, variations in the concentration and molecular distribution of specific compound classes present in SOM were caused by the acid washing of soils. As confirmed by both 13 C-CPMAS-NMR and thermochemolysis results, the molecules most susceptible to the acid treatment were the carbohydrates, lignin monomers (G14 and G15), fatty acids (C18 saturated and unsaturated), fatty acids of microbial origin (C15, C17, and C19), hydroxy acids (C16, C18), and dioic acids (C18) which represent the components weakly bound to the organic matrix. Our findings not only showed the efficacy of the decarbonation treatment of calcareous soils with 3 N HCl, but also indicated how the acidic washing can improve the differentiation of soils on the basis of SOM molecular characteristics. Graphical abstract.

Rationale: Secondary organic aerosols (SOAs) represent a significant portion of total atmospheric aerosols. They are generated by the oxidation of volatile organic compounds (VOCs), and particularly biogenic VOCs (BVOCs). The analysis of such samples is usually performed by targeted methods that often require time-consuming preparation steps that can induce loss of compounds and/or sample contaminations., Methods: Recently, untargeted methods using high-resolution mass spectrometry (HRMS) have been successfully employed for a broad characterization of chemicals in SOAs. Herein we propose a new application of the direct analysis in real time (DART) ionization method combined with HRMS to quickly detect several hundred chemicals in SOAs collected on a quartz filter without sample preparation or separation techniques., Results: The reproducibility of measurements was good, with several hundred elemental compositions common to three different replicates. The relative standard deviations of the intensities of the chemical families ranged from 6% to 35%, with sufficient sensitivity to allow the unambiguous detection of 4 ng/mm 2 of pinic acid. The presence of oligomers and specific tracers was highlighted by MS n (n ≤ 4) experiments, an achievement that is difficult to attain with other ultrahigh-resolution mass spectrometers. Contributions of this untargeted DART-HRMS method were illustrated by the analysis of fresh and aged SOAs from different gaseous precursors such as limonene, a β-pinene/limonene mixture or scots pines emissions., Conclusions: The results show that it is possible to use DART-HRMS for the identification of tracers of specific aging reactions, or for the identification of aerosols from specific biogenic precursors., (© 2018 John Wiley & Sons, Ltd.)

Cloud droplets contain dynamic and complex pools of highly heterogeneous organic matter, resulting from the dissolution of both water-soluble organic carbon in atmospheric aerosol particles and gas-phase soluble species, and are constantly impacted by chemical, photochemical, and biological transformations. Cloud samples from two summer events, characterized by different air masses and physicochemical properties, were collected at the Puy de Dôme station in France, concentrated on a strata-X solid-phase extraction cartridge and directly infused using electrospray ionization in the negative mode coupled with ultrahigh-resolution mass spectrometry. A significantly higher number (n = 5258) of monoisotopic molecular formulas, assigned to CHO, CHNO, CHSO, and CHNSO, were identified in the cloud sample whose air mass had passed over the highly urbanized Paris region (J1) compared to the cloud sample whose air mass had passed over remote areas (n = 2896; J2). Van Krevelen diagrams revealed that lignins/CRAM-like, aliphatics/proteins-like, and lipids-like compounds were the most abundant classes in both samples. Comparison of our results with previously published data sets on atmospheric aqueous media indicated that the average O/C ratios reported in this work (0.37) are similar to those reported for fog water and for biogenic aerosols but are lower than the values measured for aerosols sampled in the atmosphere and for aerosols produced artificially in environmental chambers.

A comprehensive method for the determination and characterization of 15 common explosive compounds in water samples by ultra-high pressure liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry (APCI-MS/MS) is presented. The method allows the determination of 10 nitroaromatics, two nitroamines and three nitrate ester compounds. Among these, 1,3,5-Triamino-2,4,6-trinitrobenzene (TATB) was quantified and detected for the first time in our knowledge at trace levels (0.2 µg/L). Furthermore, the collision induced dissociation (CID) mass spectrum of TATB is discussed and a fragmentation mechanism is proposed. The signal for each explosive was normalized by isotopically-enriched congeners used as internal standards. The limits of detection (LOD) reached 20 ng/L, depending on the type of energetic molecule, which are adequate for water samples and the linearity was verified from 1.4 to 2 orders of magnitude. The sensitivity of the UHPLC-APCI-MS/MS approach allows direct injection of aqueous samples without preceding extraction for concentration. Besides, the method displays a good reliability with low signal suppression in various matrices such as spring water, mineral water, acidified water or ground water. The effectiveness of the method is demonstrated by the analysis of underground water samples containing traces of explosives from test fields in France., (Copyright © 2015 Elsevier B.V. All rights reserved.)