Report of an inter-laboratory comparison from the European Union Reference Laboratory for Food Contact Materials: ILC02 2015 – Specific migration from a multilayer in food simulant A

This report presents the results of an inter-laboratory comparison on the specific migration of caprolactam (CAP) and 2,4-di-tert butyl phenol (2,4-DTBP) from a plastic food contact material in food simulant A (ethanol 10 %, v/v) organised by the EURL-FCM, Ispra (Italy). Homogeneity and stability studies were conducted. Participants had to carry out a migration test by immersion with food simulant A for 10 days at 60oC, to quantify the migration of caprolactam (CAP) in food simulant A, and to provide details of the analytical and sample extraction procedure. In addition a by-product 2,4-di-tert butyl phenol (2,4-DTBP) was also present and had to be quantified. The assigned values of the migration of the migrant were calculated as the robust mean of the results reported by the participants by applying the Q/Hampel method robust statistics. The participation to the ILC was satisfactory with 28 out of 29 participating laboratories submitting results. The z-score values of the laboratories for each substance were calculated based on the assigned value. In the case of CAP and also for the more challenging non intentionally added substances 2,4-DTBP more than 82% of the results were fully satisfactory (|z-score|<2). This percentage rose to close to 90% for z-scores <3 in the compliance evaluation of the regulated substance CAP.JRC.F.7-Knowledge for Health and Consumer Safet

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

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

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 &lt; 0.001), with higher prevalence of LSM &gt; 7.2 kPa (35.5% vs. 29%, p &lt; 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

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

BACKGROUND & AIMS: We estimated the accuracy of FibroScan vibration-controlled transient elastography controlled attenuation parameter (CAP) and liver stiffness measurements (LSMs) in assessing steatosis and fibrosis in patients with suspected 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 non-alcoholic steatohepatitis clinical research network criteria. Diagnostic accuracy was estimated using the area under the receiver operating characteristic curves (AUROC) for the categories of steatosis and fibrosis. We assessed effects of disease prevalence on positive and negative predictive values. For LSMs, 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 AUROCs of 0.87 (95% 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 cut-off 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 cut-off values for F≥F2, F≥F3 and F=F4 were 8.2 kPa, 9.7 kPa, and 13.6 kPa respectively. Applying the optimal cut-off 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 affect 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 LSMs by FibroScan to assess liver steatosis and fibrosis, respectively, with AUROC values ranging from 0.7 to 0.89. Probe type and steatosis did not affect LSMs

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

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

Achaiki Iatriki : official publication of the medical society of western Greece and Peloponnesus

In the current issue, the editorial by Cauchi et al. argues for eco-friendly measures in endoscopy and emphasies the role of healthcare providers in reducing waste. The editorial adeptly employs the three Rs (Reduce, Reuse, Recycle) framework to tackle waste management, offering practical solutions. The editorial by Milionis et al. focuses on the reverse cascade screening for paediatric familial hypercholesterolaemia (FH), which is an upcoming tool for public health. Advantages, practices, and challenges regarding FH are thoroughly discussed. Lastly, the editorial by Fousekis et al. presents the main aspects of a chronic immune-mediated cutaneous disease, dermatitis herpetiformis (DH), which constitutes an extraintestinal manifestation of celiac disease, including its diagnosis, pathogenesis, and management. Moreover, this issue includes three review articles. The review article by Krontira et al. discusses the evolving data on the epidemiology, diagnostic approach and appropriate management of foreign body and caustic substance ingestion, based on updated guidelines published by gastroenterological and endoscopic societies. The review by Halliasos et al. provides data on the clinical presentation, diagnosis, and management of metastatic acute spinal cord compression, focusing on the importance of a multidisciplinary team approach, including spine surgeons, radiation oncologists, medical oncologists, palliative care clinicians, physiotherapists, and psychologists. Lastly, the review by Schinas et al. outlines the potential of immune modulation in the treatment of infections and the need for individualised approaches in the modern world of personalised medicine by examining some of the key strategies and immune-based therapies being developed to combat infectious diseases.peer-reviewe

Development, Validation and Application of an Ultra-High-Performance Liquid Chromatography&ndash;Tandem Mass Spectrometry (UHPLC-MS/MS) Method after QuEChERS Cleanup for Selected Dichloroanilines and Phthalates in Rice Samples

Dichloroanilines and phthalic acid esters (phthalates) are food contaminants, stable in solution even at high temperatures, which exhibit considerable toxic effects, while acting as endocrine disruptors. In the present study, a quick and easy UHPLC-MS/MS method for simultaneously analyzing two dichloroanilines (3,4-DCA and 3,5-DCA) and six phthalates (DMP, DnBP, BBP, DnOP, DEHP, and mBP) in commercial rice samples was developed, validated, and applied. For the cleanup process, the methodology of quick, easy, cheap, effective, rugged, and safe (QuEChERS) was applied, whereas different dispersants (GCB, C18, and PSA) were tested. What was developed and presented had limits of detection ranging from 0.017 up to 0.12 mg/kg, recoveries (trueness) below 120%, and relative standard deviations (RSD; precision) &lt;15% for all target analytes, whilst no significant matrix effects occurred for all analytes. It was determined that the rice samples analyzed using this developed technique did not contain any of the two dichloroaniline compounds (3,4-DCA and 3,5-DCA) nor two of the six phthalate (DMP and mBP) compounds analyzed, while the levels of other phthalates (DEHP, BBP, DnBP and DnOP) were within the legal limits. The current method ensures a fast and easy approach for the high-throughput quantification of the selected food contaminants in rice

Serum adipokine levels in patients with chronic hepatitis

Adipokines are recently discovered adipose tissue hormones with systemic effects. Leptin and adiponectin have been implicated in the pathogenesis and progression of non-alcoholic fatty liver disease and chronic hepatitis C, while little is known about the role of resistin in chronic liver diseases. The potential role of adipokines on patients with chronic hepatitis B is inadequately studied. In the present study, we investigated the above three serum adipokines levels in relation to the etiology of liver disease and determined their associations with various anthropometrical, epidemiological, metabolic host factors as well as with histological severity. We prospectively evaluated 146 patients who consecutively underwent liver biopsy. Of those 146 patients, 52 had HBeAg-negative chronic hepatitis B (CHB), 70 had chronic hepatitis C (CHC) and 24 non-alcoholic steatohepatitis (NASH). Detailed epidemiological, anthropometrical and laboratory data were recorded and insulin resistance was calculated using the HOMA index. All serum adipokines levels were determined in stored serum samples using immunoenzymometric assays. Serum samples were obtained after an overnight fasting on the liver biopsy day and were stored in aliquots at -200C until assayed. Histological lesions were evaluated blindly according to Ishak’s and Brunt’s classification for CHB/CHC and NASH, respectively. Serum adipokine levels were similar between CHB and CHC, while CHB/CHC compared to NASH patients had significantly lower leptin (8.3±7.3 vs. 17.6±16.6 ng/mL, P=0.012) and higher adiponectin (10.2±5.1 vs. 7.5±4 µg/mL, P=0.018) and resistin levels (7.1±2.5 vs. 5.7±2.8 ng/mL, P=0.016). In CHB/CHC, there was no significant association between steatosis or necroinflammation and adipokines levels, while presence of moderate/severe fibrosis (stage 4-6) was associated with higher leptin and adiponectin levels in male but not in female patients. Serum leptin and resistin levels were associated with severe fibrosis in NASH patients; however due to the small sample size this finding could not be verified in multivariate analysis. Lower resistin levels were independently associated with moderate/severe fibrosis in chronic viral hepatitis irrespective of gender or other factors (adjusted odds ratio=0.788, P=0.035). In conclusion, serum adipokines levels depended on the etiology of liver disease and differed between chronic viral hepatitis and NASH, but not between CHB and CHC. In CHB/CHC, resistin levels are independently associated with fibrosis severity, while it seems to be a gender effect in the association of leptin and adiponectin levels with fibrosis.Οι λιποκίνες αποτελούν πρόσφατα ανακαλυφθείσες ορμόνες του λιπώδους ιστού με συστηματικές δράσεις. Η λεπτίνη και η αδιπονεκτίνη πιθανόν να συμμετέχουν στην παθογένεια και εξέλιξη της μη-αλκοολικής λιπώδους νόσου του ήπατος και της χρόνιας ηπατίτιδας C, ενώ τα δεδομένα για τον ενδεχόμενο ρόλο της ρεζιστίνης στις χρόνιες ηπατοπάθειες είναι ελάχιστα. Στη χρόνια ηπατίτιδα Β οι ενδεχόμενες επιδράσεις των λιποκινών δεν έχουν μελετηθεί επαρκώς. Στην παρούσα ερευνητική εργασία, διερευνήθηκε η συσχέτιση των επιπέδων ορού των τριών λιποκινών σε συνάρτηση με την αιτιολογία της ηπατικής νόσου και με ποικίλες ανθρωπομετρικές, μεταβολικές, εργαστηριακές και ιστολογικές παραμέτρους. Στη μελέτη εντάχθηκαν προοπτικά 146 ασθενείς με χρόνια ηπατοπάθεια οι οποίοι υποβλήθηκαν σε βιοψία ήπατος. Εκ των 146 ασθενών, οι 52 έπασχαν από χρόνια ηπατίτιδα Β, οι 70 από χρόνια ηπατίτιδα C και οι 24 από μη-αλκοολική στεατοηπατίτιδα. Σε κάθε ασθενή καταγράφηκαν λεπτομερή επιδημιολογικά, ανθρωπομετρικά και εργαστηριακά δεδομένα και υπολογίστηκε η αντίσταση στην ινσουλίνη με το δείκτη ΗΟΜΑ. Τα επίπεδα ορού των λιποκινών μετρήθηκαν με εμπορικά διαθέσιμες ανοσοενζυματικές μεθόδους σε δείγματα ορών των ασθενών από την ημέρα της βιοψίας. Η φύλαξη των δειγμάτων έγινε στους -200C. Η ιστολογική ταξινόμηση των βιοψιών έγινε κατά Ishak για τις χρόνιες ιογενείς ηπατίτιδες και κατά Brunt για τη μη-αλκοολική στεατοηπατίτιδα. Τα επίπεδα των λιποκινών δεν διέφεραν σημαντικά μεταξύ ασθενών με χρόνια ηπατίτιδα Β και C. Εντούτοις, ασθενείς με χρόνια ηπατίτιδα Β ή C εμφάνισαν σημαντικά χαμηλότερα επίπεδα λεπτίνης (8.3±7.3 έναντι 17.6±16.6 ng/mL, P=0.012) και υψηλότερα επίπεδα αδιπονεκτίνης (10.2±5.1 έναντι 7.5±4 µg/mL, P=0.018) και ρεζιστίνης (7.1±2.5 έναντι 5.7±2.8 ng/mL, P=0.016) σε σχέση με τους ασθενείς με μη-αλκοολική στεατοηπατίτιδα. Οι συσχετίσεις των επιπέδων λεπτίνης και αδιπονεκτίνης με την ηπατική ιστολογία στη χρόνια ιογενή ηπατίτιδα διέφεραν ανάλογα με το φύλο. Συγκεκριμένα, τα επίπεδα λεπτίνης συσχετίστηκαν ανεξάρτητα με την ίνωση μόνο στους άρρενες, ενώ αντίστοιχη συσχέτιση προέκυψε για την αδιπονεκτίνη στη μονοπαραγοντική ανάλυση. Τα επίπεδα λεπτίνης και ρεζιστίνης συσχετίστηκαν στη μονοπαραγοντική ανάλυση με τη βαρύτητα της ίνωσης στη NASH. Λόγω μικρού αριθμού ασθενών, το παραπάνω εύρημα δεν επαληθεύτηκε σε πολυπαραγοντική ανάλυση. Τέλος, τα επίπεδα ρεζιστίνης συσχετίστηκαν ανεξάρτητα με τη βαρύτητα της ίνωσης σε ασθενείς με χρόνια ιογενή ηπατίτιδα (σχετικός κίνδυνος=0.788, P=0.035). Συμπερασματικά, τα επίπεδα λιποκινών ορού εξαρτώνται από την αιτιολογία της υποκείμενης ηπατικής νόσου. Στη χρόνια ηπατίτιδα Β και C, τα επίπεδα ρεζιστίνης συσχετίζονται ανεξάρτητα με τη βαρύτητα της ίνωσης, ενώ η συσχέτιση των επιπέδων λεπτίνης και αδιπονεκτίνης με την ηπατική ιστολογία διαφέρει ανάλογα με το φύλο