Evaluation of the Risk from Potentially Toxic Elements (PTEs) in Italy's Most Consumed Processed Fish Products.

In a balanced diet, regular fish consumption provides positive outcomes for human health. On the other hand, the seafood supply chain faces a significant food safety risk due to the presence of potentially toxic elements (PTEs). In the present study, to assess the risk for Italian consumers, the concentrations of five PTEs, namely lead, chromium, cadmium, mercury, nickel, and aluminum, were determined in the three most consumed preserved fish in Italy: tuna (Thunnus albacares, Katsuwonus pelamis), mackerel (Scomber scombrus) and anchovy (Engraulis encrasicolus). Samples were collected from the national market, and the instrumental analysis was performed by inductively coupled plasma mass spectrometry (ICP-MS). The analyzed PTEs were found in all the species that were investigated. However, after considering the target hazard quotient (THQ) and the hazard index (HI), it was observed that the three fish preserves did not pose any risk of chronic toxicity for the average consumer, even at the highest concentrations detected. However, for significant consumers, mercury detected in tuna samples represented almost 90% of the tolerable weekly intake (TWI) reported by the European Food Safety Authority (EFSA), representing a matter of concern for consumers, particularly regarding developmental neurotoxicity, whose HI exceeded 111%. The acute toxicity of nickel was also considered for significant consumers at the highest concentration detected, and the margin of exposure (MOE) calculated was above 7000, much higher than the value of 30 indicated by EFSA. Due to the lack of data on non-professional carcinogenicity or human intake through foods with low cancer risk, this toxicity was not considered in the analysis of PTEs.

Quantification of cortisol and its metabolites in human urine by LC-MSn: applications in clinical diagnosis and anti-doping control.

The objective of the current research was to develop a liquid chromatography-MSn (LC-MSn) methodology for the determination of free cortisol and its 15 endogenous metabolites (6ß-hydroxycortisol, 20α-dihydrocortisol, 20α-dihydrocortisone, 20-ß-dihydrocortisol, 20ß-dihydrocortisone, prednisolone, cortisone, α-cortolone, ß-cortolone, allotetrahydrocortisol, 5α-dihydrocortisol, tetrahydrocortisol, allotetrahydrocortisone, 5ß-dihydrocortisol, tetrahydrocortisone) in human urine. Due to its optimal performance, a linear ion trap operating in ESI negative ion mode was chosen for the spectrometric analysis, performing MS3 and MS4 experiments. The method was validated for limit of detection (LOD) and limit of quantification (LOQ) (0.01 ng mL-1 and 0.05 ng mL-1, for all compounds, respectively), intra- and inter-day precision (CV = 1.4-9.2% and CV = 3.6-10.4%, respectively), intra- and inter-day accuracy (95-110%), extraction recovery (65-95%), linearity (R2 > 0.995), and matrix effect that was absent for all molecules. Additionally, for each compound, the percentage of glucuronated conjugates was estimated. The method was successfully applied to the urine (2 mL) of 50 healthy subjects (25 males, 25 females). It was also successfully employed on urine samples of two patients with Cushing syndrome and one with Addison's disease. This analytical approach could be more appropriate than commonly used determination of urinary free cortisol collected in 24-h urine. The possibility of considering the differences and relationship between cortisol and its metabolites allows analytical problems related to quantitative analysis of cortisol alone to be overcome. Furthermore, the developed method has been demonstrated as efficient for antidoping control regarding the potential abuse of corticosteroids, which could interfere with the cortisol metabolism, due to negative feedback on the hypothalamus-hypophysis-adrenal axis. Lastly, this method was found to be suitable for the follow-up of prednisolone that was particularly important considering its pseudo-endogenous origin and correlation with cortisol metabolism.

Pesticides and Environmental Contaminants in Organic Honeys According to Their Different Productive Areas toward Food Safety Protection.

Monitoring contaminant residues in honey helps to avoid risks to human health, as it is a natural product widely consumed in all population groups, including the most vulnerable, such as children and the elderly. This is important for organic honey production that may be negatively influenced by geographical area pollution. Considering the importance of collecting data on the occurrence of various xenobiotics in different geographical areas, this study aimed to investigate the presence of contaminant residues (persistent organic pollutants (POPs) and pesticides, including glyphosate and metabolites) in organic honey samples from different production areas using different analytical methods, in order to confirm their incidence and possible impact on the food safety traits of organic production. Regarding POPs, traces of benzofluoroanthene and chrysene were detected in honey from intensive orchards and arable lands. Traces of all polychlorobiphenyl (PCB) congeners were detected at different percentages in almost all of the samples, regardless of the origin area. Traces of polybromodiphenylethers (PBDE 28, 33, and 47) were found in different percentages of samples from all of the geographical areas examined. Traces of organochlorines (OCs) and organophosphates (OPs) were identified in honey samples belonging to all of the geographical areas. No glyphosate, glufosinate, and aminomethylphosphonic acid (AMPA) residues were detected.

Detection of polyphosphates in seafood and its relevance toward food safety.

Polyphosphates are permitted as food additives (Regulation EC No 1129/2011) but their undeclared utilisation is considered fraudulent. They improve water holding capacity of the seafood, preventing biochemical/physical changes during commercialization. The key objective of this study was the detection of polyphosphate in various seafood categories, by means of high-performance ion-exchange chromatography with suppressed conductometry (HPIEC-SCD) coupled to Q-Exactive Orbitrap high resolution mass spectrometry (HRMS-Orbitrap). Ten frozen cuttlefish samples did not reveal any treatment, while in ten frigate tunas, high concentration of orthophospate was found. Unambiguous hexametaphosphate presence was demonstrated in four prawn samples, while triphosphate was quantified (11.2 ± 4 ug/g) in another four prawn samples that contained orthophosphate (10225 ± 1102 ug/g), as well. Other samples sporadically encompassed polyphosphates profiles that varied according species and processing type. This analytical approach provided sustenance in better understanding regarding utilization of polyphosphates through HRMS fingerprinting of anionic species that would be specific in food safety control.

Exposure to metals and arsenic from yellow and red tuna consumption.

Tuna is one of the most frequently consumed fish and, as a predator, can biomagnify pollutants. Metal and other elements pollution is an important worldwide concern. Based on these considerations, the aim of this work was to investigate the occurrence of As, Cd, Cr, Ni, Hg and Pb in tuna coming from different FAO areas to evaluate human exposure. The analysis was performed on muscle tissues through a quadrupole inductively coupled mass spectrometry. One hundred thirty-one samples were analysed. One red tuna from the Adriatic Sea and 11 yellow tunas exceeded Pb maximum levels (MLs) with a concentration ranging 0.31-0.86 mg kg-1; three red tunas from different Mediterranean sub-areas exceeded Hg MLs, with a concentration range 1.19 to 1.80 mg kg-1. All the Hazard Indexes (HIs) were lower than one, indicating that only a negligible health hazard could derive from the ingestion of tuna, for both average and high consumers. The risk of carcinogenicity from Cr is still under debate at the concentrations detectable in food.

Detection of glyphosate and its metabolites in food of animal origin based on ion-chromatography-high resolution mass spectrometry (IC-HRMS).

Glyphosate and glufosinate are broad spectrum herbicides, widely used in agriculture and in inhabited or industrialised areas, and aminomethylphosphonic acid is a degradation product of glyphosate. In 2015, the International Agency for Research on Cancer reported that glyphosate is a probable carcinogenic. In 2017, however, a scientific opinion of the European Chemicals Agency concluded that glyphosate is not proven to be carcinogenic, mutagenic or to have negative effects on reproduction. Nevertheless, aminomethylphosphonic acid was not considered. Due to their chemical-physical characteristics, these molecules present difficulties that have not yet allowed routine monitoring to be carried out. For these reasons, we developed and validated a simple and versatile liquid extraction, before IC-HRMS analysis, of three different complex matrices: honey, bass fish and bovine muscle. Among the satisfactory validation parameters, the LOQs in the range of 4.30-9.26 ng g-1 demonstrated high method sensitivity, compared to the few works present in literature. Finally, the method was applied to real commercial samples, which showed no traces of the selected pesticides.

Distribution of POPs, pesticides and antibiotic residues in organic honeys from different production areas.

Demand for honey is increasing, especially if it is organic and if its nutritional properties are linked to untreated environments in order to guarantee quality for health. Sources of contamination of honey can be divided into environmental and apicultural. Therefore, the distribution of persistent organic pollutants, pesticides and antibiotic residues from geographical areas with different contamination sources (high anthropic impact, intensive farming, husbandry and low anthropic impact) was investigated in order to confirm the potential transfer of xenobiotics into the supply chain and to give beekeepers tools for the selection of areas dedicated to organic production. The presence of polychlorinated biphenyls, polybrominated diphenyl ether and polycyclic aromatic hydrocarbons was confirmed, not only in proximity to highly urbanised centres, where the concentrations were higher, but in all environment contexts, confirming their ubiquity. No antibiotics or neonicotinoids were detected in 95 organic honeys, demonstrating the absence of apicultural treatments and consequently the good quality of honey of different areas. These results are important due to the undefined regulatory European situation on honey antibiotic limits.

Accelerated solvent extraction by using an 'in-line' clean-up approach for multiresidue analysis of pesticides in organic honey.

The worldwide loss of honeybee colonies may be due to their exposure to several contaminants (i.e., pesticides); such contamination may also have impacts on consumers' health. Therefore, it is essential to develop quick and new methods to detect several pesticide residues in honey samples. In this study, the effectiveness of accelerated solvent extraction (ASE) was compared with QuEChERS methods for the analysis of 53 pesticides in organic honey by gas chromatography-triple quadrupole mass spectrometry. Two simple and rapid ASE methods with 'in-line' clean-up were optimised and then compared with QuEChERS. Hexane-ethyl acetate (Hex:EtAc) and Florisil were chosen as extraction solvent and retainer for the first ASE method respectively; acetonitrile and a primary-secondary amine phase (ACN-PSA) were selected for the second ASE method. The methods were validated according to the European Union SANTE/11945/2015 guidelines. The validation parameters showed that QuEChERS and ASE with PSA as retainer had better repeatability than ASE with Hex:EtAc and Florisil. In particular, QuEChERS and ASE (ACN-PSA) showed good recovery, according to the SANTE criteria, for the majority of investigated pesticides. Conversely, when ASE with Hex:EtAc and Florisil was used as the retainer, several compounds showed recoveries lower than the acceptable value of 70%. The ASE in-line method was finally applied to evaluate pesticide concentration in organic honey samples.

Bovine teeth as a novel matrix for the control of the food chain: liquid chromatography-tandem mass spectrometry detection of treatments with prednisolone, dexamethasone, estradiol, nandrolone and seven ß2-agonists.

Veterinary drugs usually have rapid clearance rates in the liver and kidney, hampering their detection in conventional matrices such as the liver or urine. Pharmacological principles such as esterification may be applied to facilitate the administration of veterinary drugs and increase drug half-life. Prednisolone, whose therapeutic administration is regulated for food producing animals in the EU, is available in its acetate form as well as nandrolone, a banned anabolic steroid, which may be obtained as nandrolone phenylpropionate and estradiol as a benzoyl ester. While the distribution and accumulation of lipophilic and hydrophilic substances in human teeth have been well documented, studies on residues in bovine teeth are lacking. We hypothesised that analysis of bovine teeth could be used to detect both regulated and banned veterinary drugs. Steroids may be illegally used as growth promoters in food producing animals, alone or combined with ß2-agonists; therefore, we developed, and validated, in accordance with the Commission Decision 2002/657/EC, two analytical confirmatory LC-MS/MS methods to detect these classes of compounds following a unique liquid extraction procedure. Finally, we analysed teeth from three male Friesian veal calves treated with intramuscular estradiol benzoate, oral prednisolone acetate or intramuscular nandrolone phenylpropionate in combination with oral ractopamine, respectively, and from seven bovines from the food chain. Teeth from treated animals were positive for their respective drugs, with the exception of nandrolone phenylpropionate. One sample from a food chain bovine was positive for isoxsuprine, one of the seven ß2-agonists studied. Non-esterified forms of the steroids were not found. These results demonstrate that bovine teeth are a suitable matrix for the determination of pseudoendogenous substances or illicit administration of veterinary drugs.

PFO closure with only fluoroscopic guidance: 7 years real-world single centre experience.

AIMS: To evaluate the safety and the efficacy of fluoroscopy-guided only (Fluo-G) and of echocardiography-guided (Echo-G; trans-esophageal echocardiography-TEE-or intracardiac echocardiography-ICE) percutaneous closure of patent foramen ovale (PFO). METHODS AND RESULTS: Single center retrospective registry enrolling 368 consecutive patients (mean age 50.5 years) who underwent PFO closure between June 2004 and December 2011. Most patients had prior cryptogenic stroke (n = 126; 34.2%), TIA (n = 218; 51.1%); some of these had recurrent neurological events [multiple strokes n = 28 (7.8%); multiple TIAs n = 72 (18.6%)]. All the patients underwent a preprocedure TEE. PFO closure was performed with Echo-G in 187 patients (50.8%) (TEE n = 69, 36.8% and ICE n = 124, 66.3%). In Fluo-G cases, PFO with atrial septal aneurysm (ASA) was significantly less present (P < 0.005) and smaller devices (<25 mm) were implanted more frequently (P < 0.001). Both fluoroscopy and total procedural time were lower in the Fluo-G group (P < 0.0001). No differences were found in terms of successful device deployment (98.3% Fluo-G vs. 98.3% Echo-G) and RtL-shunt at follow-up (11.7% Fluo-G vs. 7.6% Echo-G). The rate of conversion from Fluoro-G to Echo-G procedure was 4.4% (n = 8). At a median follow-up of 4 years, freedom from recurrent embolic events rate was similar between the two groups (Echo-G 94.5 vs. Fluo-G 95.7%). CONCLUSIONS: In our experience Fluoro-G PFO closure was performed mainly in cases of simple anatomy, with similar results in terms of safety and efficacy compared to Echo-G cases. Both fluoroscopy and total procedural times were lower in the Fluo-G cases.

Cardiac surgery for patients with heart failure due to structural heart disease in Uganda: access to surgery and outcomes.

OBJECTIVE: Few data are available on heart failure (HF) in sub-Saharan Africa. We aimed to provide a current picture of HF aetiologies in urban Uganda, access to heart surgery, and outcomes. METHODS: We prospectively collected clinical and echocardiographic data from 272 consecutive patients referred for suspected heart disease to a tertiary hospital in Kampala during seven non-governmental organisation (NGO) missions from 2009 to 2013. We focused the analysis on 140 patients who fulfilled standardised criteria of HF by echocardiography. RESULTS: Rheumatic heart disease (RHD) was the leading cause of HF in 44 (31%) patients. Among the 50 children included (age ≤ 16 years), congenital heart disease (CHD) was the first cause of HF (30 patients, 60%), followed by RHD (16 patients, 32%). RHD was the main cause of HF (30%) among the 90 adults. All 85 patients with RHD and CHD presented with an indication for heart surgery, of which 74 patients were deemed fit for intervention. Surgery was scheduled in 38 patients with RHD [86%, median age 19 years (IQR: 12-31)] and in 36 patients with CHD [88%, median age 4 years (IQR 1-5)]. Twenty-seven candidates (32%) were operated on after a median waiting time of 10 months (IQR 6-21). Sixteen (19%) had died after a median of 38 months (IQR 5-52); 19 (22%) were lost to follow up. CONCLUSION: RHD still represents the leading cause of HF in Uganda, in spite of cost-efficient prevention strategies. The majority of surgical candidates, albeit young, do not have access to treatment and present high mortality rates.

A high dose of adenosine to induce transient asystole for valvuloplasty in patients undergoing transcatheter aortic valve implantation (TAVI): is it a valid alternative to rapid pacing? A prospective pilot study.

BACKGROUND: Rapid right ventricular pacing (RRVP) at rates above 200 beats/minute is used to suppress cardiac output during balloon aortic valvuloplasty (BAV) in transcatheter aortic valve replacement (TAVI) patients. A risk of inducing myocardial ischemia with RRVP remains, especially in patients with left ventricular dysfunction. Alternatively, a transient cardiac arrest can be achieved with administration of adenosine. METHODS: The primary endpoint was successful valvuloplasty defined by complete balloon inflation and deflation across aortic valve during the transient asystole induced by adenosine. Secondary endpoints were defined as the failure of adenosine to induce asystole, the incidence of ventricular ectopic beats (VEB) during balloon inflation or deflation, and balloon displacement. RESULTS: From November 2010 to January 2011, twenty consecutive patients who underwent TAVI were included. A balloon for valvuloplasty was positioned across the aortic valve. A low-dose (24 mg, n = 10) or high-dose (36 mg, n = 10) bolus of adenosine was administrated. A single bolus of adenosine-induced atrioventricular (AV) block (mean duration, 18.6 ± 6.6 seconds) followed by cardiac asystole in 16 patients (80%) (low-dose, n = 9). A successful BAV was achieved in 12 patients (60%) (low-dose, n = 8). Adenosine induced only bradycardia in 4 patients (20%) (low-dose, n = 1). A burst of VEB during BAV occurred in all patients. Balloon displacement occurred in 6 patients (37.5%). CONCLUSION: BAV after administration of adenosine is feasible, safe, and may represent an option for high-risk TAVI patients in whom RRVP might not be well tolerated. The occurrence of ventricular ectopic contractions triggered by balloon inflation and deflations accounts for balloon displacement and crossover to RRVP.

Incidence, predictors, management, immediate and long-term outcomes following grade III coronary perforation.

OBJECTIVES: The aim of this study was to evaluate the incidence, predictors, management, and clinical outcomes in patients with grade III coronary perforation during percutaneous coronary intervention. BACKGROUND: Grade III coronary perforation is a rare but recognized complication associated with high morbidity and mortality. METHODS: From 24,465 patients undergoing percutaneous coronary intervention from May 1993 to December 2009, 56 patients had grade III coronary perforation. RESULTS: Most lesions were complex: 44.6% type B2, 51.8% type C, and 28.6% chronic total occlusions, and within a small vessel (≤ 2.5 mm) in 32.1%. Glycoprotein IIb/IIIa inhibitors were administered in 17.9% of patients. The device causing perforation was intracoronary balloon in 50%: 53.6% compliant, 46.4% noncompliant; intracoronary guidewire in 17.9%; rotablation in 3.6%; and directional atherectomy in 3.6%. Following perforation, immediate treatment and success rates, respectively, were prolonged balloon inflation 58.9%, 54.5%; covered stent implantation 46.4%, 84.6%; coronary artery bypass graft surgery (CABG) and surgical repair 16.0%, 44.4%; and coil embolization 1.8%, 100%. Multiple methods were required in 39.3%. During the procedure (n = 56), 19.6% required cardiopulmonary resuscitation and 3.6% died. In-hospital (n = 54), 3.7% required CABG, 14.8% died. The combined procedural and in-hospital myocardial infarction rate was 42.9%, and major adverse cardiac event rate was 55.4%. At clinical follow-up (n = 46) (median: 38.1 months, range 7.6 to 122.8), 4.3% had a myocardial infarction, 4.3% required CABG, and 15.2% died. The target lesion revascularization rate was 13%, with target vessel revascularization in 19.6%, and major adverse cardiac events in 41.3%. CONCLUSIONS: Grade III coronary perforation is associated with complex lesions and high acute and long-term major adverse cardiac event rates.

Clinical and angiographic outcomes after percutaneous recanalization of chronic total saphenous vein graft occlusion using modern techniques.

Poor long-term outcomes after percutaneous coronary intervention (PCI) in chronic total occlusion (CTO) of saphenous vein grafts (SVGs) have been reported. However, limited data are available evaluating the use of modern techniques in this group. The aim of the present study was to assess the efficacy and long-term outcomes of PCI in SVG CTO with the routine use of embolic protection devices and drug-eluting stents. A retrospective cohort analysis was conducted of all consecutive patients undergoing PCI to SVG CTO from May 2002 to July 2009 at 2 centers. The indication for PCI was the presence of angina or silent ischemia with evidence of inducible ischemia after functional testing in the territory supplied by the SVG, despite optimal medical therapy. We identified 34 patients with SVG CTO. Of the 34 patients, 23 (68%) underwent successful SVG recanalization with stent implantation. An embolic protection device was used in 78% and 95% of stents implanted were drug-eluting stents. No in-hospital major adverse cardiac events occurred in the successful PCI group; one myocardial infarction occurred in the unsuccessful group. At follow-up (median 18.0 months, interquartile range 10.4 to 48.3), 1 case of myocardial infarction had occurred in the successful group. The in-stent restenosis rate was 68% (n = 13), of which 77% were focal, with target vessel revascularization in 61%. In conclusion, despite the relatively low procedural success rates, the clinical outcomes after successful PCI to SVG CTO with modern techniques were favorable. The repeat revascularization rates were high; however, graft patency was achievable in most after reintervention.