A prospective study on the prevalence of MASLD in people with type-2 diabetes in the community. Cost effectiveness of screening strategies.

BACKGROUND AND AIMS: As screening for the liver disease and risk-stratification pathways are not established in patients with type-2 diabetes mellitus (T2DM), we evaluated the diagnostic performance and the cost-utility of different screening strategies for MASLD in the community. METHODS: Consecutive patients with T2DM from primary care underwent screening for liver diseases, ultrasound, ELF score and transient elastography (TE). Five strategies were compared to the standard of care: ultrasound plus abnormal liver function tests (LFTs), Fibrosis score-4 (FIB-4), NAFLD fibrosis score, Enhanced liver fibrosis test (ELF) and TE. Standard of care was defined as abnormal LFTs prompting referral to hospital. A Markov model was built based on the fibrosis stage, defined by TE. We generated the cost per quality-adjusted life year (QALY) gained and calculated the incremental cost-effectiveness ratio (ICER) over a lifetime horizon. RESULTS: Of 300 patients, 287 were included: 64% (186) had MASLD and 10% (28) had other causes of liver disease. Patients with significant fibrosis, advanced fibrosis, and cirrhosis due to MASLD were 17% (50/287), 11% (31/287) and 3% (8/287), respectively. Among those with significant fibrosis classified by LSM≥8.1 kPa, false negatives were 54% from ELF and 38% from FIB-4. On multivariate analysis, waist circumference, BMI, AST levels and education rank were independent predictors of significant and advanced fibrosis. All the screening strategies were associated with QALY gains, with TE (148.73 years) having the most substantial gains, followed by FIB-4 (134.07 years), ELF (131.68 years) and NAFLD fibrosis score (121.25 years). In the cost-utility analysis, ICER was £2480/QALY for TE, £2541.24/QALY for ELF and £2059.98/QALY for FIB-4. CONCLUSION: Screening for MASLD in the diabetic population in primary care is cost-effective and should become part of a holistic assessment. However, traditional screening strategies, including FIB-4 and ELF, underestimate the presence of significant liver disease in this setting.

Diagnostic accuracy of non-invasive tests to screen for at-risk MASH-An individual participant data meta-analysis.

BACKGROUND & AIMS: There is a need to reduce the screen failure rate (SFR) in metabolic dysfunction-associated steatohepatitis (MASH) clinical trials (MASH+F2-3; MASH+F4) and identify people with high-risk MASH (MASH+F2-4) in clinical practice. We aimed to evaluate non-invasive tests (NITs) screening approaches for these target conditions. METHODS: This was an individual participant data meta-analysis for the performance of NITs against liver biopsy for MASH+F2-4, MASH+F2-3 and MASH+F4. Index tests were the FibroScan-AST (FAST) score, liver stiffness measured using vibration-controlled transient elastography (LSM-VCTE), the fibrosis-4 score (FIB-4) and the NAFLD fibrosis score (NFS). Area under the receiver operating characteristics curve (AUROC) and thresholds including those that achieved 34% SFR were reported. RESULTS: We included 2281 unique cases. The prevalence of MASH+F2-4, MASH+F2-3 and MASH+F4 was 31%, 24% and 7%, respectively. Area under the receiver operating characteristics curves for MASH+F2-4 were .78, .75, .68 and .57 for FAST, LSM-VCTE, FIB-4 and NFS. Area under the receiver operating characteristics curves for MASH+F2-3 were .73, .67, .60, .58 for FAST, LSM-VCTE, FIB-4 and NFS. Area under the receiver operating characteristics curves for MASH+F4 were .79, .84, .81, .76 for FAST, LSM-VCTE, FIB-4 and NFS. The sequential combination of FIB-4 and LSM-VCTE for the detection of MASH+F2-3 with threshold of .7 and 3.48, and 5.9 and 20 kPa achieved SFR of 67% and sensitivity of 60%, detecting 15 true positive cases from a theoretical group of 100 participants at the prevalence of 24%. CONCLUSIONS: Sequential combinations of NITs do not compromise diagnostic performance and may reduce resource utilisation through the need of fewer LSM-VCTE examinations.

Glomerular Hyperfiltration: A Marker of Fibrosis Severity in Metabolic Associated Steatotic Liver Disease in an Adult Population.

Glomerular hyperfiltration (GH) is an increase in the glomerular filtration rate, possibly progressing to chronic kidney disease (CKD). Metabolic-associated steatotic liver disease (MASLD) is linked to an increased risk of CKD, especially if fibrosis is present; however, the association between GH and MASLD has not been explored. To evaluate GH prevalence in MASLD and its possible correlation with liver fibrosis. 772 consecutive patients with ultrasound MASLD (mean age 47.3 ± 8.9 years, 67.1% males) were enrolled. GH was defined as estimated glomerular filtration rate (eGFR) greater than the upper quartile of values in the cohort. Liver stiffness measurement (LSM) by FibroScan ≥ 7.2 kPa suggested liver fibrosis. GH was present in 20% of patients, liver fibrosis in 30%. In total, 53.4% of the cohort was obese, 40.9% hypertensive, 36.3% diabetic and 70.8% dyslipidaemic. GH patients compared to non-GH were significantly younger (38.4 ± 8.3 vs. 49.5 ± 7.7, p < 0.001), with higher prevalence of LSM > 7.2 kPa (35.5% vs. 29%, p < 0.001), without any difference in metabolic comorbidities. In multivariate analysis, age (OR 0.85, CI 95% 0.82-0.87) and significant fibrosis (OR 1.83; CI 95%1.10-3.03) remained independently associated with GH, regardless of the presence of metabolic alterations and nephrotoxic drugs. GH, an early marker of renal damage, is highly prevalent in MASLD and is associated with hepatic fibrosis. GH may be considered an early marker of both liver and renal disease and its recognition could prompt the management of risk factors aimed at preventing the progression of both hepatic and renal disease.

Liquid chromatography-mass spectrometry method for the determination of polyethylene terephthalate and polybutylene terephthalate cyclic oligomers in blood samples.

Food contact materials (FCM) polyethylene terephthalate (PET) and polybutylene terephthalate (PBT) used extensively in food packaging may contain cyclic oligomers which may migrate into food and thus cause toxic effects on human health. A simple, fast, and sensitive ultra-high-performance liquid chromatography method quadrupole time-of-flight mass spectrometer was developed for the analysis of 7 cyclic oligomers in post-mortem blood samples. The targeted analytes were separated on a Waters BEH C18 (150 × 2.1 mm, 1.7 µm) analytical column by gradient elution. Calibration curves were constructed based on standard solutions and blood samples and Student's t-test was applied to evaluate the matrix effect. The LODs ranged from 1.7 to 16.7 µg mL-1, while the method accuracy was assessed by recovery experiments and resulting within the range 84.2-114.6%. Such an analytical method for the determination of PET and PBT cyclic oligomers in biological samples is reported for the first time. The developed methodology allows the determination of these oligomers in blood providing a useful analytical tool to assess the exposure and thus the potential hazard and health risks associated with these non-intentionally added substances (NIAS) from PET and PBT FCM through food consumption. The method was validated and successfully applied to the analysis of 34 post-mortem whole blood samples. Polyethylene terephthalate trimer was detected in four of them, for the first time in literature.

Subclinical and clinical atherosclerosis in non-alcoholic fatty liver disease is associated with the presence of hypertension.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular (CV) risk. However, it is unclear whether NAFLD contributes independently to the development of CV disease. Our study aimed at assessing the differences in several indices of atherosclerosis, arterial stiffness and cardiac morphology among patients with isolated NAFLD, isolated hypertension (HT) or a combination of the two conditions. METHODS AND RESULTS: A total of 169 participants (mean age = 50.4 ± 10.2 yrs; males = 73.6%) were divided according to the presence of NAFLD and HT into three groups: only NAFLD (55 patients), only HT (49 patients), and NAFLD + HT (65 patients). Exclusion criteria were a BMI≥35 kg/m2 and a diagnosis of diabetes mellitus. Carotid ultrasonography was performed to measure markers of atherosclerosis and arterial stiffness. Cardiac remodeling was analyzed using echocardiography. The prevalence of subclinical and overt atherosclerosis was significantly higher in the NAFLD + HT patients as compared to the other two groups (atherosclerotic plaques: 43.1%, 10.9%, and 22.4% (p < 0.001) in NAFLD + HT, NAFLD, and HT groups, respectively). No differences were found among indices of arterial stiffening and cardiac remodeling across the three groups. In multivariate regression analysis, the coexistence of NAFLD and HT was an independent risk factor for overt atherosclerosis (OR = 4.88, CI 95% 1.14-20.93), while no association was found when either NAFLD or HT was considered alone. CONCLUSION: Overt atherosclerosis was significantly present only in NAFLD + HT patients, but not in patients with isolated NAFLD. This implies that the impact of NAFLD on vascular structure and function could depend on the coexistence of other major CV risk factors, such as HT.

Increased Body Mass Index and Type 2 Diabetes Are the Main Predictors of Nonalcoholic Fatty Liver Disease and Advanced Fibrosis in Liver Biopsies of Patients With Human Immunodeficiency Virus Monoinfection.

BACKGROUND: Liver disease is an important cause of morbidity and mortality in people living with human immunodeficiency virus (PLWH), of which nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized cause. There are limited data investigating NAFLD in HIV monoinfection and histologically defined disease. We aimed to identify who is at risk of fibrosis, NAFLD, and nonalcoholic steatohepatitis (NASH) among PLWH and explore the diagnostic accuracy of noninvasive markers of fibrosis. METHODS: This was a retrospective, cross-sectional, international, multicenter study including patients with HIV monoinfection, without chronic viral hepatitis or other known causes of chronic liver disease, who underwent liver biopsy for abnormal liver biochemistry and/or clinical suspicion of liver fibrosis. RESULTS: A total of 116 patients from 5 centers were included. Sixty-three (54%) had NAFLD, of whom 57 (92%) had NASH. Overall, 36 (31%) had advanced fibrosis (≥F3) and 3 (3%) had cirrhosis. Of the 53 cases without NAFLD, 15 (28%) had advanced fibrosis. Collagen proportionate area was similar between cases with and without NAFLD (3% vs 2%). Body mass index was independently associated with NAFLD (aOR, 1.2; 95% CI, 1.08-1.34), and type 2 diabetes was independently associated with advanced fibrosis (aOR, 3.42; 95% CI, 1.00-11.71). The area under the curve for advanced fibrosis was 0.65 and 0.66 for both NAFLD Fibrosis Score (NFS) and FIB-4. Cutoff values of -1.455 (NFS) and 1.3 (FIB-4) have negative-predictive values of 0.80 and 0.82, respectively. CONCLUSIONS: Advanced fibrosis is strongly associated with type 2 diabetes in PLWH. Serological markers require further optimization.

Royal Free Hospital-estimated glomerular filtration rate for prognostic stratification of first acute kidney injury in cirrhosis.

BACKGROUND & AIMS: Renal function is a major determinant of prognosis in patients with cirrhosis. Current guidelines only contemplate serum creatinine (sCr) to assess kidney injury. However, there are formulas to estimate glomerular filtration rate (eGFR) which better measure renal function in patients listed for liver transplantation. There is no data available on whether these formulas predict prognosis in patients with acute kidney injury (AKI). METHODS: In 143 patients presenting with a first episode of AKI, we compared the prognostic value of renal function estimated using sCr or eGFR assessed with Modification of Diet in Renal Disease (MDRD-6), chronic kidney disease epidemiology (CKD-EPI) and Royal Free Hospital (RFH) for renal replacement therapy (RRT) within 30 days of AKI, and 30- and 90-day transplant-free survival. RESULTS: eGFR was calculated on values obtained before and at admission, at presentation of AKI (D0) and 48 hours after AKI (D2).15% of patients (more commonly in alcohol + metabolic etiology; P = .049 vs other) required RRT. Transplant-free survival at 30-and 90-day were 77% and 63%. Among sCr, MDRD-6, CKD-EPI and RFH-eGFR, the latter predicted best RRT (HR 0.937 95% CI 0.893-0.982, P = .007), 30-d (HR 0.936 95% CI 0.901-0.972, P = .001) and 90-d (HR 0.934 95% CI 0.908-0.972, P < .001) mortality/OLT. CONCLUSIONS: Renal function estimated using the RFH-eGFR calculated at D2 after AKI diagnosis is a strong predictor of RRT and of 30-d and 90-d transplant-free survival. Results suggest that in cirrhosis, RFH-eGFR may be a better indicator of prognosis in AKI than sCr.

Food Contact Materials: Migration and Analysis. Challenges and Limitations on Identification and Quantification.

Food contact materials (FCM) are defined as the objects and materials intended to come into direct or indirect contact with foodstuff, while food contact articles are defined as objects, being equipment, containers, packaging and various utensils which are clearly intended to be used for the manufacture, preparation, conservation, flow, transport or handling of foodstuffs [...].

Identification and Analytical Characterization of a Novel Synthetic Cannabinoid-Type Substance in Herbal Material in Europe.

The rapid diffusion of new psychoactive substances (NPS) presents unprecedented challenges to both customs authorities and analytical laboratories involved in their detection and characterization. In this study an analytical approach to the identification and structural elucidation of a novel synthetic cannabimimetic, quinolin-8-yl-3-[(4,4-difluoropiperidin-1-yl) sulfonyl]-4-methylbenzoate (2F-QMPSB), detected in seized herbal material, is detailed. An acid precursor 4-methyl-3-(4,4-difluoro-1-piperidinylsulfonyl) benzoic acid (2F-MPSBA), has also been identified in the same seized material. After extraction from the herbal material the synthetic cannabimimetic, also referred to as synthetic cannabinoid receptor agonists or "synthetic cannabinoids", was characterized using gas chromatography-mass spectrometry (GC-MS), 1H, 13C, 19F and 15N nuclear magnetic resonance (NMR) and high-resolution tandem mass spectrometry (HR-MS/MS) combined with chromatographic separation. A cheminformatics platform was used to manage and interpret the analytical data from these techniques.

Gut Microbiome and Degradation Product Formation during Biodegradation of Expanded Polystyrene by Mealworm Larvae under Different Feeding Strategies.

Polystyrene (PS) is a plastic polymer extensively used for food packaging. PS is difficult to decompose and has low recycling rates, resulting in its accumulation in the environment, in the form of microplastic particles causing pollution and harming oceans and wildlife. Degradation of PS by mealworms (Tenebrio molitor) has been suggested as a possible biological strategy for plastic contamination; however, the biodegradation mechanism of PS by mealworms is poorly understood. It is hypothesized that the gut microbiome plays an important role in the degradation of PS by mealworms. This study carried out a comparative analysis of the gut microbiome of Tenebrio molitor larvae under different feeding strategies, and of the formation of degradation compounds (monomers, oligomers). A diet of bran:PS at 4:1 and 20:1 ratios was tested. The diet with the low ratio of bran:PS led to the presence of higher amounts of these compounds, compared to that with the high ratio. In addition, it was demonstrated that the addition of H2O significantly improved the biodegradation of PS monomer and oligomer residues, which could be identified only in the frass. The protein and nitrogen contents in insects' biomass and frass varied amongst treatments. The diets resulted in differences in the gut microbiota, and three potential bacterial strains were identified as candidates involved in the biodegradation of PS.

Accuracy of FibroScan Controlled Attenuation Parameter and Liver Stiffness Measurement in Assessing Steatosis and Fibrosis in Patients With Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: We estimated the accuracy of FibroScan vibration-controlled transient elastography controlled attenuation parameter (CAP) and liver stiffness measurement (LSMs) in assessing steatosis and fibrosis in patients with suspected nonalcoholic liver disease (NAFLD). METHODS: We collected data from 450 consecutive adults who underwent liver biopsy analysis for suspected NAFLD at 7 centers in the United Kingdom from March 2014 through January 2017. FibroScan examinations with M or XL probe were completed within the 2 weeks of the biopsy analysis (404 had a valid examination). The biopsies were scored by 2 blinded expert pathologists according to nonalcoholic steatohepatitis clinical research network criteria. Diagnostic accuracy was estimated using the area under the receiver operating characteristic curves (AUROCs) for the categories of steatosis and fibrosis. We assessed effects of disease prevalence on positive and negative predictive values. For LSM, the effects of histological parameters and probe type were appraised using multivariable analysis. RESULTS: Using biopsy analysis as the reference standard, we found that CAP identified patients with steatosis with an AUROC of 0.87 (95% confidence interval [CI] 0.82-0.92) for S≥S1, 0.77 (95% CI 0.71-0.82) for S≥S2, and 0.70 (95% CI 0.64-0.75) for S=S3. Youden cutoff values for S≥S1, S≥S2, and S≥S3 were 302 dB/m, 331 dB/m, and 337 dB/m, respectively. LSM identified patients with fibrosis with AUROCs of 0.77 (95% CI 0.72-0.82) for F≥F2, 0.80 (95% CI 0.75-0.84) for F≥F3, and 0.89 (95% CI 0.84-0.93) for F=F4. Youden cutoff values for F≥F2, F≥F3, and F=F4 were 8.2 kPa, 9.7 kPa, and 13.6 kPa, respectively. Applying the optimal cutoff values, determined from this cohort, to populations of lower fibrosis prevalence increased negative predictive values and reduced positive predictive values. Multivariable analysis found that the only parameter that significantly affected LSMs was fibrosis stage (P<10-16); we found no association with steatosis or probe type. CONCLUSIONS: In a prospective analysis of patients with NAFLD, we found CAP and LSM by FibroScan to assess liver steatosis and fibrosis, respectively, with AUROC values ranging from 0.70 to 0.89. Probe type and steatosis did not affect LSM. STUDY REGISTRATION: ClinicalTrials.gov Identifier: NCT01985009.

Development and validation of a multi-analyte GC-MS method for the determination of 84 substances from plastic food contact materials.

Chemical substances shall not migrate from food contact materials (FCM) at levels that are potentially harmful for the consumers. Each of the current analytical methods applied to verify the migration of substances from FCM covers only one or few substances. There is a very limited number of publications on the development of analytical methods allowing the simultaneous determination of several classes of FCM substances, and almost none of them reported methods entirely dedicated to the ones in the positive list of Commission Regulation (EU) No. 10/2011 for plastic FCMs. Therefore, a simple, sensitive and reliable multi-analyte method was developed for the analysis of FCM substances in food simulants. It employs an optimised liquid-liquid extraction with dichloromethane as extraction solvent in the presence of 10% m/v NaCl, followed by quantitative analysis with gas chromatography coupled to mass spectrometry (GC-MS). A combination of total ion chromatograms (TICs) and extracted ion chromatograms (EICs) was used. The optimisation and validation of the method have been carried out according to current international guidelines. Adequate sensitivity was demonstrated in the selected concentration ranges for most of the analytes, with limits of quantification (LOQs) at least three times lower than the legislative limit, when existing. The results showed that the method is sufficiently accurate for the majority of substances, with recoveries between 70 and 115% and relative standard deviations (RSDs) smaller than 20% at three concentration levels. The method was applied to the analysis of some FCM multilayers. The method allows, for the first time, the simultaneous quantification of 84 FCM substances in two of the official food simulants (A and C) at levels of a few ng g-1. Graphical abstract.

Identification of 1-Butyl-Lysergic Acid Diethylamide (1B-LSD) in Seized Blotter Paper Using an Integrated Workflow of Analytical Techniques and Chemo-Informatics.

The rapid dispersion of new psychoactive substances (NPS) presents challenges to customs services and analytical laboratories, which are involved in their detection and characterization. When the seized material is limited in quantity or of a complex nature, or when the target substance is present in very small amounts, the need to use advanced analytical techniques, efficient workflows and chemo-informatics tools is essential for the complete identification and elucidation of these substances. The current work describes the application of such a workflow in the analysis of a single blotter paper, seized by Swedish customs, that led to the identification of a lysergic acid diethylamide (LSD) derivative, 1-butyl-lysergic acid diethylamide (1B-LSD). Such blotter paper generally contains an amount in the range of 30-100 ug. This substance, which is closely related to 1-propionyl-lysergic acid diethylamide (1P-LSD), seems to have only recently reached the drug street market. Its identification was made possible by comprehensively combining gas chromatography with mass spectrometry detection (GC-MS), liquid chromatography coupled with high-resolution tandem MS (LC-HR-MS/MS), Orbitrap-MS and both 1D and 2D nuclear-magnetic-resonance (NMR) spectroscopy. All the obtained data have been managed, assessed, processed and evaluated using a chemo-informatics platform to produce the effective chemical and structural identification of 1B-LSD in the seized material.

Investigation and management of a raised serum ferritin.

Serum ferritin level is one of the most commonly requested investigations in both primary and secondary care. Whilst low serum ferritin levels invariably indicate reduced iron stores, raised serum ferritin levels can be due to multiple different aetiologies, including iron overload, inflammation, liver or renal disease, malignancy, and the recently described metabolic syndrome. A key test in the further investigation of an unexpected raised serum ferritin is the serum transferrin saturation. This guideline reviews the investigation and management of a raised serum ferritin level. The investigation and management of genetic haemochromatosis is not dealt with however and is the subject of a separate guideline.

Intention-to-treat survival benefit of liver transplantation in patients with hepatocellular cancer.

The debate about the best approach to select patients with hepatocellular cancer (HCC) waiting for liver transplantation (LT) is still ongoing. This study aims to identify the best variables allowing to discriminate between "high-" and "low-benefit" patients. To do so, the concept of intention-to-treat (ITT) survival benefit of LT has been created. Data of 2,103 adult HCC patients consecutively enlisted during the period 1987-2015 were analyzed. Three rigorous statistical steps were used in order to create the ITT survival benefit of LT: the development of an ITT LT and a non-LT survival model, and the individual prediction of the ITT survival benefit of LT defined as the difference between the median ITT survival with (based on the first model) and without LT (based on the second model) calculated for each enrolled patient. Four variables (Model for End-Stage Liver Disease, alpha-fetoprotein, Milan-Criteria status, and radiological response) displayed a high effect in terms of delta benefit. According to these risk factors, four benefit groups were identified. Patients with three to four factors ("no-benefit group"; n = 405 of 2,103; 19.2%) had no benefit of LT compared to alternative treatments. Conversely, patients without any risk factor ("large-benefit group"; n = 108; 5.1%) yielded the highest benefit from LT reaching 60 months. CONCLUSION: The ITT transplant survival benefit presented here allows physicians to better select HCC patients waiting for LT. The obtained stratification may lead to an improved and more equitable method of organ allocation. Patients without benefit should be de-listed, whereas patients with large benefit ratio should be prioritized for LT. (Hepatology 2017;66:1910-1919).

Validation of the Baveno VI criteria to identify low risk cirrhotic patients not requiring endoscopic surveillance for varices.

BACKGROUND & AIMS: The Baveno VI guidelines propose that cirrhotic patients with a liver stiffness measurement (LSM) <20kPa and a platelet count >150,000/µl can avoid screening endoscopy as their combination is highly specific for excluding clinically significant varices. The aim of the study was to validate these criteria. METHODS: Transient elastography data was collected from two institutions from 2006-2015. Inclusion criteria were a LSM ⩾10kPa and an upper gastrointestinal endoscopy within 12months, with a diagnosis of compensated chronic liver disease. Exclusion criteria were porto-mesenteric-splenic vein thrombosis and non-cirrhotic portal hypertension. Varices were graded as low risk (grade <2) or high risk (grade ⩾2). RESULTS: The study included 310 patients (169 (55%) hepatitis C, and 275 (89%) Child-Pugh A). Varices were present in 23% cases, with 5% prevalence of high risk varices. Overall 102/310 (33%) met the Baveno VI criteria. Within this group 11% had varices and 2% had high risk varices, representing 2/15 (13%) of all high risk varices. The Baveno VI criteria gave a sensitivity 0.87, specificity 0.34, positive predictive value 0.06, negative predictive value 0.98, positive likelihood ratio 1.31 and negative likelihood ratio 0.39. The AUROC for LSM and platelet count combined was 0.746. CONCLUSIONS: The Baveno VI criteria performed well correctly identifying 98% of patients who could safely avoid endoscopy. LAY SUMMARY: This study examines the effectives of a recent set of guidelines published by the Baveno VI conference, which states that patients with chronic liver disease and a low liver stiffness (<20kPa) and high platelet count (>150) are at low risk of having varices and do not need a screening endoscopy. Varices are a complication of cirrhosis, confer a risk of serious bleeding, and can be diagnosed and treated by endoscopy. Our study reviewed the clinical records of patients who have had liver stiffness scans and endoscopy over a 9-year period at two hospitals. The results show that only about 2% of patients who meet the Baveno VI criteria will be miss-classified as not having varices.

Microplastics and nanoplastics: Exposure and toxicological effects require important analysis considerations.

Microplastics (MPs) and nanoplastics (NPs) pervade both the environment and the food chain, originating from the degradation of plastic materials from various sources. Their ubiquitous presence raises concerns for ecosystem safety, as well as the health of animals and humans. While evidence suggests their infiltration into mammalian and human tissues and their association with several diseases, the precise toxicological effects remain elusive and require further investigation. MPs and NPs sample preparation and analytical methods are quite scattered without harmonized strategies to exist at the moment. A significant challenge lies in the limited availability of methods for the chemical characterization and quantification of these contaminants. MPs and NPs can undergo further degradation, driven by abiotic or biotic factors, resulting in the formation of cyclic or linear oligomers. These oligomers can serve as indicative markers for the presence or exposure to MPs and NPs. Moreover, recent finding concerning the aggregation of oligomers to form NPs, makes their analysis as markers very important. Recent advancements have led to the development of sensitive and robust analytical methods for identifying and (semi)quantifying these oligomers in environmental, food, and biological samples. These methods offer a valuable complementary approach for determining the presence of MPs and NPs and assessing their risk to human health and the environment.

Partitioning and in vitro bioaccessibility of apple polyphenols during mechanical and physiological extraction: A hierarchical clustering analysis with LC-ESI-QTOF-MS/MS.

Polyphenol partitioning during mechanical (cold-pressing) and physiological (digestion) extraction at the individual polyphenol and subclass level was investigated. UHPLC-ESI-QTOF-MS/MS analysis yielded a comprehensive identification of 45 polyphenols whose semi-quantification revealed a hierarchical clustering strongly determined by polyphenol structure and their location within the apple tissue. For instance, pomace retained most flavonols and flavanols (degree of polymerization DP 5-7), which were highly hydrophobic, hydroxylated, or large (>434 Da), and more abundant in peel. In vitro digestion UHPLC-ESI-QTOF-MS/MS analysis of whole apple (and its corresponding matrix-free extract) clustered polyphenols into five main groups according to their interaction with plant cell walls (PCWs) during each digestion phase. This grouping was not reproduced in pomace, which exhibited a greater matrix effect than whole apple during oral and gastric digestion. Nevertheless, the interaction between most polyphenol groups, including dihydrochalcones, flavanols (DP 1-4) and hydroxycinnamic acid derivatives, and pomace PCWs was lost during intestinal digestion.

Analysis of oligomers to assess exposure to microplastics from foods. A perspective.

There is an emerging interest in evaluating the presence of microplastic (MP) and nanoplastic (NP) residues in food. Despite their potential threat to human health, there is still a need for harmonized methods to evaluate and quantify their presence. Incomplete polymerization may occur during the production of plastic. Conversely, oligomers are formed during chemical, mechanical, or enzymatic depolymerization. Oligomers are a few nanometers in size. Recent advances in analytical chemistry have enabled the quantification and identification of these oligomers in various complex biological matrices. Therefore, we propose that the specific nanosized oligomers can be considered markers for the presence of MPs/NPs. This advance may facilitate a broader perspective for the assessment of MPs/NPs exposure, leading to the evaluation of food safety and associated risks to humans.