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Laryngeal tuberculosis (LT), a rare but possible manifestation of extrapulmonary tuberculosis (TBC) and the most frequent granulomatous disease of the larynx, is slowly resurfacing due to the worldwide recrudescence of TBC. We present the case of a 59 y-o Caucasian woman, non-smoker, with no history of recent travels in endemic areas, affected by pulmonary sarcoidosis, that presented with a symptomatic vegetating lesion involving the left free margin of the epiglottic and a small, ulcerated lesion over the right arytenoid mucosa. While the patient's profile would not lead to a primary suspect of laryngeal TBC, the diagnostic workup and histological examination confirmed the unusual finding, and the patient was started on standard antitubercular therapy, with a complete laryngeal response. Although isolated laryngeal tuberculosis is still a rare finding, it should be kept into consideration also in non-endemic areas, especially in patients with chronic disease requiring immunosuppressive drugs., Competing Interests: We have no conflict of interest to declare., (© The Author(s) 2024. Published by Oxford University Press.)

Satellite DNA sequences are an integral part of centromeres, regions critical for faithful segregation of chromosomes during cell division. Because of their complex repetitive structure, satellite DNA may act as a barrier to DNA replication and other DNA based transactions ultimately resulting in chromosome breakage. Over the past two decades, several DNA repair proteins have been shown to bind and function at centromeres. While the importance of these repair factors is highlighted by various structural and numerical chromosome aberrations resulting from their inactivation, their roles in helping to maintain genome stability by solving the intrinsic difficulties of satellite DNA replication or promoting their repair are just starting to emerge. In this review, we summarize the current knowledge on the role of DNA repair and DNA damage response proteins in maintaining the structure and function of centromeres in different contexts. We also report the recent connection between the roles of specific DNA repair factors at these genomic loci with age-related increase of chromosomal instability under physiological and pathological conditions., 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 © 2023 Elsevier Ltd. All rights reserved.)

EFSA was asked for a scientific opinion on the risks for animal and human health related to the presence of polychlorinated naphthalenes (PCNs) in feed and food. The assessment focused on hexaCNs due to very limited data on other PCN congeners. For hexaCNs in feed, 217 analytical results were used to estimate dietary exposures for food-producing and non-food-producing animals; however, a risk characterisation could not be performed because none of the toxicological studies allowed identification of reference points. The oral repeated dose toxicity studies performed in rats with a hexaCN mixture containing all 10 hexaCNs indicated that the critical target was the haematological system. A BMDL 20 of 0.05 mg/kg body weight (bw) per day was identified for a considerable decrease in the platelet count. For hexaCNs in food, 2317 analytical results were used to estimate dietary exposures across dietary surveys and age groups. The highest exposure ranged from 0.91 to 29.8 pg/kg bw per day in general population and from 220 to 559 pg/kg bw per day for breast-fed infants with the highest consumption of breast milk. Applying a margin of exposure (MOE) approach, the estimated MOEs for the high dietary exposures ranged from 1,700,000 to 55,000,000 for the general population and from 90,000 to 230,000 for breast-fed infants with the highest consumption of breast milk. These MOEs are far above the minimum MOE of 2000 that does not raise a health concern. Taking account of the uncertainties affecting the assessment, the Panel concluded with at least 99% certainty that dietary exposure to hexaCNs does not raise a health concern for any of the population groups considered. Due to major limitations in the available data, no assessment was possible for genotoxic effects or for health risks of PCNs other than hexaCNs., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

The European Commission asked EFSA to update its 2011 risk assessment on polybrominated diphenyl ethers (PBDEs) in food, focusing on 10 congeners: BDE-28 , - 47 , - 49 , - 99 , - 100 , - 138 , - 153 , - 154 , - 183 and ‑ 209 . The CONTAM Panel concluded that the neurodevelopmental effects on behaviour and reproductive/developmental effects are the critical effects in rodent studies. For four congeners ( BDE-47 , - 99 , - 153 , - 209 ) the Panel derived Reference Points, i.e. benchmark doses and corresponding lower 95% confidence limits (BMDLs), for endpoint-specific benchmark responses. Since repeated exposure to PBDEs results in accumulation of these chemicals in the body, the Panel estimated the body burden at the BMDL in rodents, and the chronic intake that would lead to the same body burden in humans. For the remaining six congeners no studies were available to identify Reference Points. The Panel concluded that there is scientific basis for inclusion of all 10 congeners in a common assessment group and performed a combined risk assessment. The Panel concluded that the combined margin of exposure (MOET) approach was the most appropriate risk metric and applied a tiered approach to the risk characterisation. Over 84,000 analytical results for the 10 congeners in food were used to estimate the exposure across dietary surveys and age groups of the European population. The most important contributors to the chronic dietary Lower Bound exposure to PBDEs were meat and meat products and fish and seafood. Taking into account the uncertainties affecting the assessment, the Panel concluded that it is likely that current dietary exposure to PBDEs in the European population raises a health concern., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

The European Commission requested EFSA to provide an update of the 2012 Scientific Opinion of the Panel on Contaminants in the Food Chain (CONTAM) on the risks for animal health related to the presence of ergot alkaloids (EAs) in feed. EAs are produced by several fungi of the Claviceps and Epichloë genera. This Opinion focussed on the 14 EAs produced by C. purpurea (ergocristine, ergotamine, ergocornine, α- and β-ergocryptine, ergometrine, ergosine and their corresponding 'inine' epimers). Effects observed with EAs from C. africana (mainly dihydroergosine) and Epichloë (ergovaline/-inine) were also evaluated. There is limited information on toxicokinetics in food and non-food producing animals. However, transfer from feed to food of animal origin is negligible. The major effects of EAs are related to vasoconstriction and are exaggerated during extreme temperatures. In addition, EAs cause a decrease in prolactin, resulting in a reduced milk production. Based on the sum of the EAs, the Panel considered the following as Reference Points (RPs) in complete feed for adverse animal health effects: for pigs and piglets 0.6 mg/kg, for chickens for fattening and hens 2.1 and 3.7 mg/kg, respectively, for ducks 0.2 mg/kg, bovines 0.1 mg/kg and sheep 0.3 mg/kg. A total of 19,023 analytical results on EAs (only from C. purpurea ) in feed materials and compound feeds were available for the exposure assessment (1580 samples). Dietary exposure was assessed using two feeding scenarios (model diets and compound feeds). Risk characterisation was done for the animals for which an RP could be identified. The CONTAM Panel considers that, based on exposure from model diets, the presence of EAs in feed raises a health concern in piglets, pigs for fattening, sows and bovines, while for chickens for fattening, laying hens, ducks, ovines and caprines, the health concern related to EAs in feed is low., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

The European Commission asked EFSA to update its 2009 risk assessment on arsenic in food carrying out a hazard assessment of inorganic arsenic (iAs) and using the revised exposure assessment issued by EFSA in 2021. Epidemiological studies show that the chronic intake of iAs via diet and/or drinking water is associated with increased risk of several adverse outcomes including cancers of the skin, bladder and lung. The CONTAM Panel used the benchmark dose lower confidence limit based on a benchmark response (BMR) of 5% (relative increase of the background incidence after adjustment for confounders, BMDL 05 ) of 0.06 μg iAs/kg bw per day obtained from a study on skin cancer as a Reference Point (RP). Inorganic As is a genotoxic carcinogen with additional epigenetic effects and the CONTAM Panel applied a margin of exposure (MOE) approach for the risk characterisation. In adults, the MOEs are low (range between 2 and 0.4 for mean consumers and between 0.9 and 0.2 at the 95th percentile exposure, respectively) and as such raise a health concern despite the uncertainties., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

This statement provides scientific guidance on the information needed to support the risk assessment of the detoxification processes applied to products intended for animal feed in line with the acceptability criteria of the Commission Regulation (EU) 2015/786., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

In 2004, the EFSA Panel on Contaminants in the Food Chain (CONTAM) adopted a Scientific Opinion on the risks to animal health and transfer from feed to food of animal origin related to the presence of ochratoxin A (OTA) in feed. The European Commission requested EFSA to assess newly available scientific information and to update the 2004 Scientific Opinion. OTA is produced by several fungi of the genera Aspergillus and Penicillium . In most animal species it is rapidly and extensively absorbed in the gastro-intestinal tract, binds strongly to plasma albumins and is mainly detoxified to ochratoxin alpha (OTalpha) by ruminal microbiota. In pigs, OTA has been found mainly in liver and kidney. Transfer of OTA from feed to milk in ruminants and donkeys as well as to eggs from poultry is confirmed but low. Overall, OTA impairs function and structure of kidneys and liver, causes immunosuppression and affects the zootechnical performance (e.g. body weight gain, feed/gain ratio, etc.), with monogastric species being more susceptible than ruminants because of limited detoxification to OTalpha. The CONTAM Panel considered as reference point (RP) for adverse animal health effects: for pigs and rabbits 0.01 mg OTA/kg feed, for chickens for fattening and hens 0.03 mg OTA/kg feed. A total of 9,184 analytical results on OTA in feed, expressed in dry matter, were available. Dietary exposure was assessed using different scenarios based on either model diets or compound feed (complete feed or complementary feed plus forage). Risk characterisation was made for the animals for which an RP could be identified. The CONTAM Panel considers that the risk related to OTA in feed for adverse health effects for pigs, chickens for fattening, hens and rabbits is low., (© 2023 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

Chronic rhinosinusitis (CRS) is a complex and heterogeneous disorder whose etiopathogenetic picture is not yet completely known and is classically divided into CRS with (CRSwNP) and without nasal polyps (CRSsNP). But today the distinction is made with type 2 and nontype 2 variants. A rational and defined pathway for the diagnosis of chronic rhinosinusitis is an indispensable means to be able to arrive at a correct identification of the patient. This typing is essential to be able to arrive at the correct course of treatment, which turns out to be different for different types of patients. For this reason, the realization of a diagnostic therapeutic pathway represents a fundamental way for the otolaryngologist specialist but not only, since today diagnostics has a multidisciplinary framework. In the present work, precise indications have been developed to arrive at a correct diagnosis. The various diagnostic pathways and processes to arrive at a correct therapeutic framing have been highlighted. Therapy ranging from medical therapy to surgical therapy without neglecting the new biological therapies. It does not represent a guideline but a diagnostic method that can be adapted to all the various territorial realities., Competing Interests: The 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., (© 2023 Canevari, Giorli, Monti, Biagini, Bagnasco, Cavaliere, Pipolo, De Corso, Gelardi, Gramellini, loppi, La Mantia, Malvezzi, Bignami, Dehgani-Mobaraki, Seccia, Maggiore, Macchi.)

Mineral oil hydrocarbons (MOH) are composed of saturated hydrocarbons (MOSH) and aromatic hydrocarbons (MOAH). Due to the complexity of the MOH composition, their complete chemical characterisation is not possible. MOSH accumulation is observed in various tissues, with species-specific differences. Formation of liver epithelioid lipogranulomas and inflammation, as well as increased liver and spleen weights, are observed in Fischer 344 (F344) rats, but not in Sprague-Dawley (SD) rats. These effects are related to specific accumulation of wax components in the liver of F344 rats, which is not observed in SD rats or humans. The CONTAM Panel concluded that F344 rats are not an appropriate model for effects of MOSH with wax components. A NOAEL of 236 mg/kg body weight (bw) per day, corresponding to the highest tested dose in F344 rats of a white mineral oil product virtually free of wax components, was selected as relevant reference point (RP). The highest dietary exposure to MOSH was estimated for the young population, with lower bound-upper bound (LB-UB) means and 95th percentiles of 0.085-0.126 and 0.157-0.212 mg/kg bw per day, respectively. Considering a margin of exposure approach, the Panel concluded that the present dietary exposure to MOSH does not raise concern for human health for all age classes. Genotoxicity and carcinogenicity are associated with MOAH with three or more aromatic rings. For this subfraction, a surrogate RP of 0.49 mg/kg bw per day, calculated from data on eight polycyclic aromatic hydrocarbons, was considered. The highest dietary exposure to MOAH was also in the young population, with LB-UB mean and 95th percentile estimations of 0.003-0.031 and 0.011-0.059 mg/kg bw per day, respectively. Based on two scenarios on three or more ring MOAH contents in the diet and lacking toxicological information on effects of 1 and 2 ring MOAH, a possible concern for human health was raised., (© 2023 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

The European Commission requested EFSA to provide an assessment of the processing conditions which make Ambrosia seeds non-viable in feed materials and compound feed. This assessment also includes information on a reliable procedure to verify the non-viability of the seeds. Ambrosia seeds are known contaminants in feed with maximum levels set in the Directive 2002/32/EC. The manufacturing processes and processing conditions applied to the feed may affect the viability of the Ambrosia seeds. Therefore, the CONTAM Panel compared these conditions with conditions that have been shown to be sufficient to render Ambrosia seeds non-viable. The Panel concluded with a certainty of 99-100% that solvent extraction and toasting of oilseed meals at temperatures of 120°C with steam injection for 10 min or more will make Ambrosia seeds non-viable. Since milling/grinding feed materials for compound feed of piglets, aquatic species and non-food producing animals would not allow particles of sizes ≥1 mm (the minimum size of viable Ambrosia seeds) passing the grinding process it was considered very likely (with ≥ 90% certainty) that these feeds will not contain viable Ambrosia seeds. In poultry, pig, and possibly cattle feed, particle sizes are ≥ 1 mm and therefore Ambrosia seeds could likely (66-90% certainty) survive the grinding process. Starch and gluten either from corn or wheat wet milling would not contain Ambrosia seeds with 99-100% certainty. Finally, ensiling fresh forages contaminated with A. artemisiifolia seeds for more than 3 months is very likely to render all seeds non-viable. The Panel concluded that a combination of the germination test and a subsequent triphenyl-tetrazolium-chloride (TTC) test will very likely (with ≥ 90% certainty) verify the non-viability of Ambrosia seeds. The Panel recommends that data on the presence of viable Ambrosia seeds before and after the different feed production processes should be generated., (© 2023 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

Background: Juvenile nasopharyngeal angiofibroma (JNA) is a rare tumor that mainly affects young boys. Its intervention may be complex due to its high vascularity, location, and extension. Preoperative embolization is used to prevent intrasurgical and postsurgical bleeding. Two main kinds of embolization are described in literature: intratumoral and transarterial, and numerous embolic materials are used. Case Presentation . We want to present a case of presurgical embolization of a stage IV JNA, performed using a single stop-flow balloon assisted technique with the balloon cuffed exclusively in the external carotid artery and using Onyx 18 as an embolic agent., Conclusions: The embolization with an exclusive external carotid artery single stop-flow technique using Onyx 18 is a safe, effective, and a definitive approach., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Eliodoro Faiella et al.)

Frontal sinus involvement by malignant tumors is a rare finding. Therefore, a systematic literature review along with a personal case series may contribute to defining more accurately the epidemiology, treatment options, and outcomes of these neoplasms. This is a retrospective review of patients affected by frontal sinus malignancies surgically treated in a tertiary-care referral center over a period of 20 years. Moreover, a systematic literature review of studies describing frontal sinus cancers from 2000 to date was performed according to PRISMA guidelines in order to analyze current evidence about the treatment and outcomes of such a rare disease. Our retrospective review was basedon 84 cases, treated with an exclusive endoscopic approach in 43 cases (51.2%), endoscopic approach with frontal osteoplastic flap in 6 cases (7.1%), and transfacial or transcranial approaches in 35 cases (41.7%). The five-year overall, disease-specific, disease-free, and recurrence-free survivals were 54.6%, 62.6%, 33.1%, and 59.1%, respectively. Age, dural involvement, type of surgical resection, and surgical margin status were significantly associated with the survival endpoints. In conclusion, the involvement of the frontal sinus is associated with a poor prognosis. Multidisciplinary management, including specific histology-driven treatments, represents the gold standard for improving outcomes and minimizing morbidity.

In 2015, EFSA established a temporary tolerable daily intake (t-TDI) for BPA of 4 μg/kg body weight (bw) per day. In 2016, the European Commission mandated EFSA to re-evaluate the risks to public health from the presence of BPA in foodstuffs and to establish a tolerable daily intake (TDI). For this re-evaluation, a pre-established protocol was used that had undergone public consultation. The CEP Panel concluded that it is Unlikely to Very Unlikely that BPA presents a genotoxic hazard through a direct mechanism. Taking into consideration the evidence from animal data and support from human observational studies, the immune system was identified as most sensitive to BPA exposure. An effect on Th17 cells in mice was identified as the critical effect; these cells are pivotal in cellular immune mechanisms and involved in the development of inflammatory conditions, including autoimmunity and lung inflammation. A reference point (RP) of 8.2 ng/kg bw per day, expressed as human equivalent dose, was identified for the critical effect. Uncertainty analysis assessed a probability of 57-73% that the lowest estimated Benchmark Dose (BMD) for other health effects was below the RP based on Th17 cells. In view of this, the CEP Panel judged that an additional uncertainty factor (UF) of 2 was needed for establishing the TDI. Applying an overall UF of 50 to the RP, a TDI of 0.2 ng BPA/kg bw per day was established. Comparison of this TDI with the dietary exposure estimates from the 2015 EFSA opinion showed that both the mean and the 95th percentile dietary exposures in all age groups exceeded the TDI by two to three orders of magnitude. Even considering the uncertainty in the exposure assessment, the exceedance being so large, the CEP Panel concluded that there is a health concern from dietary BPA exposure., (© 2023 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

Objective: To retrospectively review the experience of five tertiary-care university hospitals on frontal sinus revision surgery with osteoplastic flap (OPF)., Methods: Descriptive analysis of patients who underwent frontal sinus surgery with OPF after one or more endoscopic procedures for benign and inflammatory pathologies from 2000 to 2022. Clinical charts were reviewed for demographics, indications, clinical presentation, previous frontal procedures, OPF technique and outcomes., Results: Of the 124 patients who underwent an OPF procedure, 33 met inclusion criteria. With a mean of 2.1 previous endoscopic surgeries, Draf III was the most common former procedure. In 30 (91%) cases OPF was part of a combined procedure. The most common indications were inverted papilloma (61%), mucocele (9%) and chronic rhinosinusitis (6%). Frontal outflow stenosis (36%) and mucocele (9%) were the most frequent complications observed. Improvement of overall symptoms and patient satisfaction after the OPF procedure were recorded., Conclusions: Even in the endoscopic era, OPF still represents a paramount procedure that should be included in the rhino-surgeon's armamentarium, in particular in patients with challenging pathologies and anatomy when previous endoscopic endonasal attempts have failed., (Copyright © 2023 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

EFSA was asked for a scientific opinion on the risks to public health related to the presence of N -nitrosamines ( N -NAs) in food. The risk assessment was confined to those 10 carcinogenic N -NAs occurring in food (TCNAs), i.e. NDMA, NMEA, NDEA, NDPA, NDBA, NMA, NSAR, NMOR, NPIP and NPYR. N -NAs are genotoxic and induce liver tumours in rodents. The in vivo data available to derive potency factors are limited, and therefore, equal potency of TCNAs was assumed. The lower confidence limit of the benchmark dose at 10% (BMDL 10 ) was 10 μg/kg body weight (bw) per day, derived from the incidence of rat liver tumours (benign and malignant) induced by NDEA and used in a margin of exposure (MOE) approach. Analytical results on the occurrence of N -NAs were extracted from the EFSA occurrence database (n = 2,817) and the literature (n = 4,003). Occurrence data were available for five food categories across TCNAs. Dietary exposure was assessed for two scenarios, excluding (scenario 1) and including (scenario 2) cooked unprocessed meat and fish. TCNAs exposure ranged from 0 to 208.9 ng/kg bw per day across surveys, age groups and scenarios. 'Meat and meat products' is the main food category contributing to TCNA exposure. MOEs ranged from 3,337 to 48 at the P95 exposure excluding some infant surveys with P95 exposure equal to zero. Two major uncertainties were (i) the high number of left censored data and (ii) the lack of data on important food categories. The CONTAM Panel concluded that the MOE for TCNAs at the P95 exposure is highly likely (98-100% certain) to be less than 10,000 for all age groups, which raises a health concern., (© 2023 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

The European Commission asked EFSA for a scientific opinion on the risks for human health of the presence of grayanotoxins (GTXs) in 'certain honey' from Ericaceae plants. The risk assessment included all structurally related grayananes occurring with GTXs in 'certain' honey. Oral exposure is associated with acute intoxication in humans. Acute symptoms affect the muscles, nervous and cardiovascular systems. These may lead to complete atrioventricular block, convulsions, mental confusion, agitation, syncope and respiratory depression. For acute effects, the CONTAM Panel derived a reference point (RP) of 15.3 μg/kg body weight for the sum of GTX I and III based on a BMDL 10 for reduced heart rate in rats. A similar relative potency was considered for GTX I. Without chronic toxicity studies, an RP for long-term effects could not be derived. There is evidence for genotoxicity in mice exposed to GTX III or honey containing GTX I and III, showing increased levels of chromosomal damage. The mechanism of genotoxicity is unknown. Without representative occurrence data for the sum of GTX I and III and consumption data from Ericaceae honey, acute dietary exposure was estimated based on selected concentrations for GTX I and III reflecting concentrations measured in 'certain' honeys. Applying a margin of exposure (MOE) approach, the estimated MOEs raised health concerns for acute toxicity. The Panel calculated the highest concentrations for GTX I and III below which no acute effects would be expected following 'certain honey' consumption. The Panel is 75% or more certain that the calculated highest concentration of 0.05 mg for the sum of GTX I and III per kg honey is protective for all age groups regarding acute intoxications. This value does not consider other grayananes in 'certain honey' and does not cover the identified genotoxicity., (© 2023 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

In 2017, the EFSA Panel on Contaminants in the Food Chain (CONTAM) adopted a Scientific Opinion on the risks for animal health related to the presence of deoxynivalenol (DON) and its acetylated and modified forms in food and feed. No observed adverse effect levels (NOAELs) and lowest observed adverse effect levels (LOAELs) were derived for different animal species. For horses, an NOAEL of 36 mg DON/kg feed was established, the highest concentration tested and not showing adverse effects. For poultry, an NOAEL of 5 mg DON/kg feed for broiler chickens and laying hens, and an NOAEL of 7 mg DON/kg feed for ducks and turkeys was derived. The European Commission requested EFSA to review the information regarding the toxicity of DON for horses and poultry and to revise, if necessary, the established reference points (RPs). Adverse effect levels of 1.9 and 1.7 mg DON/kg feed for, respectively, broiler chickens and turkeys were derived from reassessment of existing studies and newly available literature, showing that DON causes effects on the intestines, in particular the jejunum, with a decreased villus height but also histological damage. An RP for adverse animal health effects of 0.6 mg/kg feed for broiler chickens and turkeys, respectively, was established. For horses, an adverse effect level of 5.6 mg DON/kg feed was established from studies showing reduced feed intake, with an RP for adverse animal health effects of 3.5 mg/kg feed. For ducks and laying hens, RPs remain unchanged. Based on mean and P95 (UB) exposure estimates performed in the previous Opinion, the risk of adverse health effects of feeds containing DON was considered a potential concern for broiler chickens and turkeys. For horses, the risk for adverse health effects from feed containing DON is low., (© 2023 Wiley‐VCH Verlag GmbH & Co. KgaA on behalf of the European Food Safety Authority.)

Purpose of Review: Despite the impressive evolutions in endoscopic endonasal approaches and instrumentations, the frontal sinus remains a challenging area. Different surgical options have been described over the years, but the main criticism lies in choosing the most suitable approach for a given case, based on the anatomy of each patient and the disease to treat. The purpose of this study is to provide a comprehensive review of surgical access strategies currently available to address the frontal sinus, including both endonasal and traditional external procedures, analysing indications, contraindications, complications and outcomes., Recent Findings: Frontal sinus surgery includes minimally invasive endonasal approaches (balloon dilatation, Draf type I); extended endonasal approaches (Draf type IIA-IIB-IIC, Draf type III and their modifications via orbital transposition and contralateral pyriform aperture resection); external procedures (superior eyelid incision, frontal osteoplastic flap, Riedel procedure, Riedel-Mosher operation); and combined approaches., Summary: Recent advances in endoscopic endonasal techniques have deeply reshaped the surgical options to manage frontal sinus diseases, in an attempt to minimize the invasiveness of the procedures and maximize their outcomes. Traditional external procedures should be used in selected cases nonamenable for endonasal surgery. The appropriate selection of cases appears to be of paramount importance to obtain successful outcomes., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Biphenotypic sinonasal sarcoma (BSNS) is a rare low-grade cancer that was included from the 4th edition of WHO classification of head and neck tumours. The purpose of this study is to analyse clinical behaviour, pattern of recurrences and survival outcomes of this neoplasm., Methods: Retrospective review of patients affected by BSNS who were treated via an endoscopic-assisted approach in 6 European tertiary-care referral hospitals. Cases of BSNS described in literature since 2012 to date were fully reviewed, according to PRISMA guidelines., Results: A total of 15 patients were included. Seven patients were treated via an endoscopic endonasal approach, 4 with endoscopic transnasal craniectomy, and 4 via a cranio-endoscopic approach. Adjuvant treatment was delivered in 2 cases. After a mean follow-up of 27.3 months, systemic metastasis was observed in 1 case; the 5-year overall survival and disease-free survival rates were 100% and 80 ± 17.9%, respectively., Conclusions: BSNS is a locally aggressive tumour with a low recurrence rate and encouraging survival outcomes if properly treated with surgical resection and free margins followed by adjuvant radiotherapy for selected cases. Endoscopic-assisted surgery is safe and effective as an upfront treatment within a multidisciplinary care protocol., (Copyright © 2022 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Objectives: The improvements in survival with expansion of the survivors' population, along with evolution of endoscopically-based treatment modalities, have contributed to emphasize the clinical relevance of recurrences in sinonasal cancers. However, at present, literature is scant regarding the pattern of recurrences and the therapeutic strategies available to manage long survivors who experienced single or multiple failures. The aim of the present study was to analyze sinonasal cancers recurrences to provide data regarding rates and patterns of relapse, predictors of failure and prognostic impact of the recurrence., Materials and Methods: All patients receiving multimodal treatments including endoscopic surgery between 1995 and 2021 in three European referral centers were included. Statistical analysis of survival was performed through univariable, multivariable and unidirectional multistate models. Survival after recurrence analysis was implemented for patients experiencing at least one recurrence., Results: The 5- and 10-year recurrence free survival rates were 34.1% and 38.4% for the whole population. With a mean follow-up time of 60 months, a global recurrence rate of 32.9% was observed. The 5- and 10-year survival after recurrence rates were 27.2% and 21.7%, respectively. Incidence and rates of recurrences were significantly associated with histology subtypes., Conclusion: This study provides valuable oncologic outcomes regarding a large homogenous cohort of patients affected by sinonasal malignances treated within a multimodal framework, emphasizing the strong correlation of histologic type with prognosis, as well as with pattern of recurrences., 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 © 2022 Elsevier Ltd. All rights reserved.)

In 2011, the EFSA Panel on Contaminants in the Food Chain (CONTAM) adopted a Scientific Opinion on the risks for animal health related to the presence of T-2 (T2) and HT-2 (HT2) toxin in food and feed. No observed adverse effect levels (NOAELs) and lowest observed adverse effect levels (LOAELs) were derived for different animal species. In ruminants a LOAEL was established for the sum of T2 and HT2 of 0.3 mg/kg body weight (bw) per day, based on studies with calves and lambs. The CONTAM Panel noted that the effects observed in nutritionally challenged heifers and ewes give rise to the assumption that rumen detoxification of T2 may not always be complete and therefore effective to prevent adverse effects in ruminants. However, the limited data on the effects of T2 on adult ruminants did not allow a conclusion. The European Commission requested EFSA to review the information regarding the toxicity of T2 and HT2 for ruminants and to revise, if necessary, the established Reference Point (RP). Adverse effect levels of 0.001 and 0.01 mg T2/kg bw per day for, respectively, sheep and cows, were derived from case studies, estimated to correspond to feed concentrations of 0.035 mg T2/kg for sheep and 0.6 mg T2/kg for cows. RPs for adverse animal health effects of 0.01 mg/kg feed for sheep and 0.2 mg/kg feed for cows were established. For goats, the RP for cows was selected, in the absence of data that they are more sensitive. Based on mean exposure estimates performed in the previous Opinion, the risk of adverse health effects of feeds containing T2 and HT2 was considered a concern for lactating sheep. For milking goats, a comparison performed between dietary exposure and the RP derived for cows, indicates a potential risk for adverse health effects. For dairy cows and fattening beef, the risk is considered low., (© 2022 Wiley‐VCH Verlag GmbH & Co. KgaA on behalf of the European Food Safety Authority.)

Following a request from the European Commission, the EFSA Panel on Contaminants in the Food Chain (CONTAM) assessed a decontamination process of fish oils and vegetable oils and fats to reduce the concentrations of dioxins (polychlorinated dibenzo- p -dioxins and polychlorinated dibenzofurans, abbreviated together as PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) by adsorption to activated carbon. All feed decontamination processes must comply with the acceptability criteria specified in the Commission Regulation (EU) 2015/786. Data provided by the feed food business operator (FBO) were assessed for the efficacy of the process and to demonstrate that the process did not adversely affect the characteristics and properties of the product. The limited information provided, in particular on the analysis of the samples before and after decontamination, did not allow the CONTAM Panel to conclude whether or not the proposed decontamination process is effective in reducing PCDD/Fs and DL-PCBs in the fish- and vegetable oils and fats. Although there is no evidence from the data provided that the decontamination process leads to detrimental changes in the nutritional composition of the fish- and vegetable oils, it is possible that the process could deplete some beneficial constituents (e.g. vitamins). Taken together, it was not possible for the CONTAM Panel to conclude that the decontamination process as proposed by the FBO is compliant with the acceptability criteria provided for in Commission Regulation (EU) 2015/786 of 19 May 2015., (© 2022 Wiley‐VCH Verlag GmbH & Co. KgaA on behalf of the European Food Safety Authority.)

Purpose: This study aimed to examine the relationship between the sphenoid sinus (SS) and surrounding vital structures such as the internal carotid artery (ICA) and optic nerve canal (ONC) as well as the types of attachment of the sphenoidal septa onto these structures., Methods: In total, 230 computed tomography (CT) scans were reviewed to study the type of sphenoid sinus pneumatization (SSP), the protrusion and dehiscence of the ICA and ONC, the relationship between the sphenoidal septa and surrounding vital structures as well as pterygoid recess pneumatization (PRP)., Results: The most common SSP was sellar type (58.7%). The rates of protrusion and dehiscence of the ICA were 26.3 and 0.4%, and for the ONC, they were 13 and 1.5%, respectively. The ICA and ONC were most protruded and dehiscent in more extensive SSP. In 21.6% of patients, the intersphenoidal septa (IS) were attached to the wall of the ICA and in 8.6% they were attached to the wall of the ONC. The attachment of IS to the ICA correlated statistically significantly (p < 0.0001) with protrusion of the ICA. Accessory septa were detected in 30.4% of cases with various sites of attachment., Conclusion: To reduce the risk of injury and complications during endoscopic sinus surgery (ESS), surgeons should consider using CT to identify possible bulging and dehiscence of the ICA/ONC and their relationship to the extent of SSP and also to establish the presence of deviation of the sphenoid septum, and the presence of accessory septa., (© 2022. The Author(s).)

Background: Solitary fibrous tumor (SFT) is a rare spindle-cell neoplasm [1]. Although typically originating from pleura, head and neck presentation accounts for about 6-18 % and very few cases have been described in paravertebral and posterior neck spaces [2]. Both computed tomography (CT) scans and magnetic resonance imaging (MRI) help in differential diagnosis of such lesion [3]. However, only histological and immunohistochemical studies give a conclusive diagnosis: CD34, BCL-2, and in particular STAT6 stainings are strongly orientative [4]. Radical surgery with free margin excision is the first treatment option, rarely requiring adjuvant therapy [2]. Prognosis is typically good and strictly related to histological risk assessment [5]. Rare cases of local recurrence and distant metastasis have been described in literature [2]., Objective: The purpose of this video is to describe the operative technique of a transcervical removal of a rare case of right paravertebral SFT. We present the diagnostic flowchart, management strategies, surgical technique and we provide anatomical dissection parallelism, which might be of interest to the readers., Materials and Methods: A 59-years-old man with a one-year right cervical asymptomatic swelling was referred to our department. A contrasted MRI documented an expansive 6.5 cm capsulated lesion in the deep posterior neck spaces with diffuse contrast enhancement and inhomogeneous appearance. A core needle biopsy was performed, and the results from the initial immunohistochemical panel were not univocal showing positivity for cytokeratins AE1/AE3, PAX8, and no reactivity for CD34. A second immunohistochemical panel was then performed, displaying diffuse nuclear positivity for STAT6, which is a surrogate marker for the NAB2-STAT6 gene fusion, a specific driver mutation of SFT. Therefore, a radical excision was performed via transcervical approach (Video 1). No post-operative complications neither cranio-cervical neurological deficit occurred., Results: In comparison to pre-operative histopathologic study, the definitive histological examination of the whole mass revealed a more classical morphology of SFT. It was classified as an intermediate risk SFT [5]. A complete free margin excision was confirmed. After a multidisciplinary discussion, no adjuvant therapies were suggested. A six- and twelve-months radiological follow-up with MRI showed no evidence of disease., Conclusion: SFT may represent a misdiagnosed entity in head and neck spaces and a correct diagnosis through immunohistochemistry is mandatory. Radical excision with free surgical margins should be pursued as adequate goal. Since SFTs show variable risk of metastatic disease, adjuvant radiotherapy should be contemplated in high-risk diseases and a clinico-radiological follow-up with MRI is required., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In 2018, the EFSA Panel on Contaminants in the Food Chain (CONTAM) adopted a Scientific Opinion on the risks for animal health related to the presence of fumonisins, their modified forms and hidden forms in feed. A no observed adverse effect level (NOAEL) of 1 mg/kg feed was established for pigs. In poultry a NOAEL of 20 mg/kg feed and in horses a reference point for adverse animal health effect of 8.8 mg/kg feed was established, referred to as NOAEL. The European Commission (EC) requested EFSA to review the information regarding the toxicity of fumonisins for pigs, poultry and horses and to revise, if necessary, the established NOAELs. The EFSA CONTAM Panel considered that the term reference point (RP) for adverse animal health effects better reflects the uncertainties in the available studies. New evidence which had become available since the previous opinion allowed to revise an RP for adverse animal health effects for poultry from 20 mg/kg to 1 mg/kg feed (based on a LOAEL of 2.5 mg/kg feed for reduced intestinal crypt depth) and for horses from 8.8 to 1.0 mg/kg feed (based on case studies on equine leukoencephalomalacia (ELEM)). For pigs, the previously established NOAEL was confirmed as no further studies suitable for deriving an RP for adverse animal health effects could be identified. Based on exposure estimates performed in the previous opinion, the risk of adverse health effects of feeds containing FB1-3 was considered a concern for poultry, when taking into account the RP of 1 mg/kg feed for intestinal effects. For horses and other solipeds, the risk is considered low, although a large uncertainty associated with exposure was identified. The same conclusions apply to the sum of FB1-3 and their hidden forms., (© 2022 Wiley‐VCH Verlag GmbH & Co. KgaA on behalf of the European Food Safety Authority.)

Background: Over the last 2 decades, transnasal endoscopic surgery (TES) has become the most frequently employed surgical technique to treat sinonasal malignancies. The rarity and heterogeneity of sinonasal cancers have hampered large non-population-based analyses., Methodology: All patients receiving TES-including treatment between 1995 and 2021 in 5 referral hospitals were included. A prognostic study was performed, and multivariable models were transformed into nomograms. Training and validation sets were based on results from 3 European and 2 non-European centres, respectively., Results: The training and validation set included 940 and 420 patients, respectively. The mean age at surgery, primary-versus-recurrent presentation, histology distribution, type of surgery, T category and type of adjuvant treatment were differently distributed in the training and validation set. In the training set, 5-year overall survival and recurrence-free survival with a 95%-confidence interval were 72.7% (69.5-76.0%) and 66.4% (63.1-69.8%), respectively, significantly varying with histology. At multivariable analyses, age, gender, previous treatment, the extent of resection on the cranial, lateral and posterolateral axes, grade/subtype, T category, nodal status, margin status and adjuvant treatment were all associated with different prognostic outcomes, displaying a heterogeneous significance and effect size according to histology. The internal and external validation of nomograms was satisfactory (optimism-corrected C-index >0.7 and cumulative area under curve >0.7) for all histologies but mucosal melanoma., Conclusions: Outcomes of TES-based treatment of sinonasal cancers vary substantially with histology. This large, non-population-based study provides benchmark data on the prognosis of sinonasal cancers that are deemed suitable for treatment including TES., Competing Interests: Conflict of interest statement 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 © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

hMTH1 protects against mutation during oxidative stress. It degrades 8-oxodGTP to exclude potentially mutagenic oxidized guanine from DNA. hMTH1 expression is linked to ageing. Its downregulation in cultured cells accelerates RAS-induced senescence, and its overexpression in hMTH1-Tg mice extends lifespan. In this study, we analysed the effects of a brief (5 weeks) high-fat diet challenge (HFD) in young (2 months old) and adult (7 months old) wild-type (WT) and hMTH1-Tg mice. We report that at 2 months, hMTH1 overexpression ameliorated HFD-induced weight gain, changes in liver metabolism related to mitochondrial dysfunction and oxidative stress. It prevented DNA damage as quantified by a comet assay. At 7 months old, these HFD-induced effects were less severe and hMTH1-Tg and WT mice responded similarly. hMTH1 overexpression conferred lifelong protection against micronucleus induction, however. Since the canonical activity of hMTH1 is mutation prevention, we conclude that hMTH1 protects young mice against HFD by reducing genome instability during the early period of rapid growth and maximal gene expression. hMTH1 protection is redundant in the largely non-growing, differentiated tissues of adult mice. In hMTH1-Tg mice, expression of a less heavily mutated genome throughout life provides a plausible explanation for their extended longevity., (© 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Introduction: Previous studies have reported a diverse range of threshold values for blood eosinophilia. In addition, a single predictive biomarker for eosinophilic chronic rhinosinusitis (CRS) with nasal polyps (ECRSwNP) has not yet been identified., Objectives: The aim of this study is to compare the clinical characteristics of ECRSwNP and non-ECRSwNP to evaluate the preoperative risk of tissue eosinophilia of chronic rhinosinusitis with nasal polyps (CRSwNP) through a multiparametric statistical analysis., Methods: One hundred ten patients with evidence of chronic polypoid rhinosinusitis were included in this study and clinical records were retrospectively reviewed. Eosinophilic CRSwNP was diagnosed based on the presence of at least 10 eosinophils per high-power field. The demographic and clinical features of ECRSwNP and non-ECRSwNP are described. The values of blood eosinophilia as predictors of tissue eosinophilia have been identified using receiver operating characteristic curves. As the predictive value of the identified cutoff through regression analysis was low, we evaluated whether other risk factors could be statistically associated with ECRSwNP, and from this, a new predictive model was proposed for the identification of eosinophilic nasal polyps before surgery., Results: We found that the best method for predicting ECRSwNP is based on a model having asthma, blood eosinophil percentage, posterior ethmoid value in Lund-Mackay score, and modified Lund-Kennedy score as explanatory variables., Conclusions: This study provides new data for a better understanding of the polypoid CRS endotypes, and the proposed model allows the endotype to be identified preoperatively.

Objectives/hypothesis: The aim of the present study is to validate and compare four of the most widely used staging systems for juvenile angiofibroma on a homogeneous cohort of patients., Study Design: Retrospective case series., Methods: A retrospective review of patients treated with endoscopic or endoscopic-assisted surgical resection between 1999 and 2020 was carried out. Each case was classified according to the following staging systems: Andrews-Fisch (1989), Radkowski (1996), University of Pittsburgh Medical Center (2010), and Janakiram (2017). Spearman's rank correlation test and areas under the curve of receiver operator curves were used to assess the correlation between outcomes of interests (blood loss, surgical time, need for transfusion, and persistence of disease) and stage of disease., Results: Seventy-nine patients were included, with a median follow-up time of 25 months (range 12-127 months). Median surgical time was 217 minutes (range 52-625). Median blood loss was 500 mL (range 40-5200) and 27 patients (34.2%) required blood transfusions. Seven patients (8.9%) showed persistence of disease. All classification systems showed a similar association with blood loss, surgical time, persistence of disease, and need for transfusion., Conclusions: Involvement of the infratemporal fossa and intracranial extension was identified as red flags for surgical planning and preoperative counseling, as associated with increased risk for transfusion and persistent/recurrent disease, respectively. No classification system was found to be better than the others in predicting the most important outcomes. Therefore, the simplest and most easily applicable system would be the preferred one to be used in clinical practice., Level of Evidence: 4 Laryngoscope, 132:1160-1165, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

EFSA was requested to deliver a statement on a recent publication revisiting the evidence for genotoxicity of acrylamide (AA). The statement was prepared by a Working Group and was endorsed by the CONTAM Panel before its final approval. In interpreting the Terms of Reference, the statement considered the modes of action underlying the carcinogenicity of AA including genotoxic and non-genotoxic effects. Relevant publications since the 2015 CONTAM Panel Opinion on AA in food were reviewed. Several new studies reported positive results on the clastogenic and mutagenic properties of AA and its active metabolite glycidamide (GA). DNA adducts of GA were induced by AA exposure in experimental animals and have also been observed in humans. In addition to the genotoxicity of AA, there is evidence for both secondary DNA oxidation via generation of reactive oxygen species and for non-genotoxic effects which may contribute to carcinogenesis by AA. These studies extend the information assessed by the CONTAM Panel in its 2015 Opinion, and support its conclusions. That Opinion applied the margin of exposure (MOE) approach, as recommended in the EFSA Guidance for substances that are both genotoxic and carcinogenic, for risk characterisation of the neoplastic effects of AA. Based on the new data evaluated, the MOE approach is still considered appropriate, and an update of the 2015 Opinion is not required at the present time., (© 2022 Wiley‐VCH Verlag GmbH & Co. KgaA on behalf of the European Food Safety Authority.)

The European Commission has asked the EFSA to evaluate the risk for animal health related to the presence of hydroxymethylfurfural (HMF) in honey bee feed. HMF is a degradation product of particular sugars and can be present in bee feed. HMF is of low acute toxicity in bees but causes increased mortality upon chronic exposure. A benchmark dose lower limit 10% (BMDL 10 ) of 1.16 μg HMF per bee per day has been calculated from mortalities observed in a 20-day study and established as a Reference Point covering also mortality in larvae, drones and queens for which no or insufficient toxicity data were available. Winter bees have a much longer lifespan than summer bees and HMF shows clear time reinforced toxicity (TRT) characteristics. Therefore, additional Reference Point intervals of 0.21-3.1, 0.091-1.1 and 0.019-0.35 µg HMF/bee per day were calculated based on extrapolation to exposure durations of 50, 90 and 180 days, respectively. A total of 219 analytical data of HMF concentrations in bee feed from EU Member States and 88 from Industry were available. Exposure estimates of worker bees and larvae ranged between 0.1 and 0.48, and between 0.1 and 0.51 μg HMF/per day, respectively. They were well below the BMDL 10 of 1.16 μg HMF/bee per day, and thus, no concern was identified. However, when accounting for TRT, the probability that exposures were below established reference point intervals was assessed to be extremely unlikely to almost certain depending on exposure duration. A concern for bee health was identified when bees are exposed to HMF contaminated bee feed for several months., (© 2022 Wiley‐VCH Verlag GmbH & Co. KgaA on behalf of the European Food Safety Authority.)

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of 2-methyloxolane as an extraction solvent under the intended conditions of use and the maximum residue limits (MRLs) proposed by the applicant. 2-Methyloxolane is intended to be used in processes currently applying hexane for oil and protein extraction from plant sources or for extraction of food additives. The proposed MRLs for the following uses are: (i) 1 mg/kg in fat, oil or butter; (ii) 10 mg/kg in defatted protein products, defatted flour and other defatted solid ingredients; (iii) 1 mg/kg in food category 13 (foods intended for particular nutritional uses as defined by Directive 2009/39/EC); and (iv) 1 mg/kg for the extraction of food additives. The Panel calculated the dietary exposure with the highest potential maximum (95th percentile) for toddlers as 0.32 mg/kg body weight (bw) per day. Based on the available toxicological data, the Panel concluded that 2-methyloxolane was rapidly metabolised with a low bioaccumulation potential and does not raise a concern for genotoxicity. The Panel identified different no observed adverse effect levels (NOAELs) in a subchronic oral toxicity study in rats, an oral developmental toxicity study and an extended one-generation reproductive toxicity study, and a TDI of 1 mg/kg bw per day for 2-methyloxolane was derived based on the lowest identified NOAEL (100 mg/kg bw per day) for reproductive and developmental toxicity. This TDI was not exceeded in any of the population groups at the mean and 95th percentile exposure. The Panel concluded that the extraction solvent 2-methyloxolane does not raise a safety concern when used according to the intended conditions and at the proposed MRLs in the extracted foods or food ingredients., (© 2022 Wiley‐VCH Verlag GmbH & Co. KgaA on behalf of the European Food Safety Authority.)

Background: Nasoseptal perforation repair is a challenging condition with no standard technique for repair recognized., Methods: A case series of consecutive patients who underwent nasoseptal perforation repair with an anterior ethmoidal artery flap was conducted. Demographic data, preoperative features of the perforation and postoperative outcomes were analyzed. Closure rate, complications and persistence of nasal symptoms were documented., Results: Thirty-two patients were included in the study. The average perforation diameter was 1.48 cm (range: 0.4-3 cm). Iatrogenic trauma was the most common cause (56% of patients). Nine cases ended up being idiopathic. The overall closure rate was 81%, but 87.5% when perforation had a 2-cm diameter or less. Of the six failures, 2 were due to flap necrosis and 4 to a residual anterior perforation. Despite the persistence, 2 patients solved their symptoms. One patient underwent revision surgery., Conclusion: The anterior ethmoidal artery flap is a reliable and minimal invasive technique for closure of symptomatic perforations. For defects larger than 2 cm, a lower success rate and additional reconstructive measures should be considered. Objective questionnaires are needed in order to evaluate functional outcomes.

Objectives/hypothesis: Maxillary cancers are rare and aggressive tumors, which can spread beyond the sinus bony walls. Preoperative assessment of infiltration of maxillary sinus floor (MSF) is paramount for surgical planning, as palatomaxillary demolition significantly impacts patients' quality of life. This study investigates the challenges involved in the preoperative and intraoperative evaluation of MSF infiltration and analyzes its prognostic relevance., Study Design: Retrospective case series., Methods: A retrospective review of patients treated for sinonasal malignancies at a single Institution was performed. Patients receiving surgical-based treatment with curative intent for primary maxillary sinus cancers, between January 2000 and November 2019, were included., Results: A cohort of 118 patients was analyzed. By comparing intraoperative findings (endoscopic assessment and frozen sections) with preoperative radiological assessment, diagnostic changes with regard to MSF infiltration were found in 27.1% (32/118 cases). MSF infiltration negatively affected the prognosis in both univariate and multivariate analyses in the overall population. In the subgroup of pT1-T3 tumors, MSF infiltration was significantly associated with reduced overall (P = .012), disease-free (P = .011), and distant recurrence-free (P = .002) survival rates. Conversely, pT classification was not able to stratify patients according to prognosis, mainly because early-staged cancers (pT1-T2) with MSF infiltration showed reduced survival rates, similar to those observed in pT3 cancers., Conclusions: Preoperative imaging should be integrated with intraoperative findings based on endoscopic inspection and frozen sections. Future studies are required to investigate the opportunity to incorporate MSF infiltration in the TNM staging system, considering its crucial role in defining the extent of surgery and its potential as prognosticator., Level of Evidence: 4 Laryngoscope, 132:26-35, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Following a request from the European Commission, the EFSA Panel on Contaminants in the Food Chain (CONTAM) provided a scientific opinion on an application for a detoxification process of groundnut press cake for aflatoxins by ammoniation. Specifically, it is required that the feed decontamination process is compliant with the acceptability criteria specified in the Commission Regulation (EU) 2015/786 of 19 May 2015. The CONTAM Panel assessed the data provided by the feed business operator with respect to the efficacy of the process to remove the contaminant from groundnut press cake batches and on information demonstrating that the process does not adversely affect the characteristics and the nature of the product. Although according to the literature the process may be able to reduce aflatoxin levels below the legal limits, the Panel concluded that the proposed decontamination process, on the basis of the experimental data submitted by the feed business operator, cannot be confirmed for compliance with the acceptability criteria provided for in Commission Regulation (EU) 2015/786 of 19 May 2015. The Panel recommended sufficient sample testing before and after the process, under the selected conditions, to ensure that the process is reproducible and reliable and to demonstrate that the detoxification is not reversible. In addition, genotoxicity testing of extracts of the treated feedingstuff and of the identified degradation products would be necessary. Finally, information on the transfer rate of AFB1 to AFM1 excretion in milk for animals fed the ammoniated product, in comparison to the starting material and on the ammoniation process changes of the nutritional values of the feed material should be provided., (© 2021 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Background: Recent developments in endoscopic sinus surgery (ESS) have increased the need to investigate the complex anatomic variations in the ethmoid roof and skull base, to inform the surgeon about the risk of damaging these crucial areas during ESS., Objective: To offer a detailed description of sinus anatomy focusing on the key surgical landmarks in ESS and frontal recess surgery to standardize a systematic approach during the preoperative sinuses imaging evaluation. Methodology: A total of 220 computed tomography (CT) scans were reviewed to obtain six sets of measurements: the depth of the cribriform plate (CP); the length of the lateral lamella of the cribriform plate (LLCP); the angle formed by the LLCP and the continuation of the horizontal plane passing through the CP; the position of the anterior ethmoidal artery (AEA) at the skull base; the extent of frontal sinus pneumatization (FSP); the type of superior attachment of the uncinate process (SAUP)., Results: The length of the LLCP was statistically significantly correlated with the different Keros classification types, the angle formed by the LLCP with the continuation of the horizontal plane passing through the CP, and with the AEA position at the skull base. The depth of the olfactory fossa was correlated with FSP., Conclusions: According to the Keros and Gera classifications, the data obtained from these evaluations allow the assessment of anatomic-radiological risk profiles and can help identify those patients who are high risk for ethmoid roof injury.

Furan is a volatile compound that is formed in foods during thermal processing. It is classified as a possible human carcinogen by international authorities based on sufficient evidence of carcinogenicity from studies in experimental animals. Although a vast number of studies both in vitro and in vivo have been performed to investigate furan genotoxicity, the results are inconsistent, and its carcinogenic mode of action remains to be clarified. Here, we address the mutagenic and clastogenic activity of furan and its prime reactive metabolite cis-2 butene-1,4-dial (BDA) in mammalian cells in culture and in mouse animal models in a search for DNA lesions responsible of these effects. To this aim, Fanconi anemia-derived human cell lines defective in the repair of DNA inter-strand crosslinks (ICLs) and Ogg1 -/- mice defective in the removal of 8-hydroxyguanine from DNA, were used. We show that both furan and BDA present a weak (if any) mutagenic activity but are clear inducers of clastogenic damage. ICLs are strongly indicated as key lesions for chromosomal damage whereas oxidized base lesions are unlikely to play a critical role.

Objective: This paper highlights the management of 5 patients affected by symptomatic ecchordosis physaliphora (EP), treated via endoscopic endonasal transsphenoidal-transclival approach and contextual multilayer skull base reconstruction. A detailed analysis of each case is provided, along with the review of the current body of literature., Methods: A retrospective review of patients treated by means of endoscopic endonasal approach for EP from 2010 to 2020 in the Otolaryngology and Neurosurgery Departments of a tertiary-care referral center for endoscopic skull base surgery was analyzed. Only adult patients with a definitive histopathological and immunohistochemical diagnosis of EP were included in the study. A systematic literature review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed for EP., Results: Five cases of EP were retrieved and included in the study. Four patients presented with CSF leakage: in two cases after minor head trauma, in one case with associated bacterial meningitis, and in one case as only referred symptom. One patient complained diplopia due to VI cranial nerve palsy. No complications or recurrences of the disease were observed after a median follow-up of 37.2 months (range, 18-72 months). A total of 27 studies were identified with the systematic literature review, encompassing 30 patients affected by symptomatic EP who were addressed to surgical treatment. Twenty-five patients underwent complete surgical removal of the EP, while in 5 cases, only subtotal resection was performed., Conclusions: EP might result in a "locus minoris resistentiae" of the skull base, predisposing, in rare cases, to CSF leakage and meningitis, spontaneously or after minor trauma. In cases of symptomatic EP, endoscopic endonasal transsphenoidal-transclival approach represents a safe and effective technique for both EP resection and contextual skull base reconstruction., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Juvenile nasopharyngeal angiofibroma (JNA) is a benign tumor of the nasal cavity that predominantly affects young boys. Surgical removal remains the gold standard for the management of this disease. Preoperative intra-arterial embolization (PIAE) is useful for reductions in intraoperative blood loss and surgical complications. In our series of 79 patients who underwent preoperative embolization from 1999 to 2020, demographics, procedural aspects, surgical management and follow-up outcome were analyzed. Embolization was performed in a similar fashion for all patients, with a superselective microcatheterization of external carotid artery (ECA) feeders and an injection of polyvinyl alcohol (PVA) particles, followed, in some cases, by the deployment of coils . Procedural success was reached in 100% of cases, with no complications such as bleeding or thromboembolic occlusion, and surgical intraoperative blood loss was significantly decreased. In conclusion, PIAE is a safe and effective technique in JNA treatment, minimizing intraoperative bleeding.

EFSA was asked by the European Commission to provide information on the levels of domoic acid (DA) in whole scallops that would ensure that levels in edible parts are below the regulatory limit after shucking. This should include five species of scallops. In addition, EFSA was asked to recommend the number of scallops to be used in an analytical sample. To address these questions, EFSA received suitable data on DA for only one scallop species, Pecten maximus , i.e. data on pooled samples of edible and non-edible parts. A large part of the concentration levels was above the limit of quantification (LOQ) and only these data were used for the assessment. Shucking in most cases resulted in a strong decrease in the toxin levels. Statistical analysis of the data showed that levels in whole scallops should not exceed 24 mg DA/kg, 59 mg DA/kg and 127 mg DA/kg to ensure that levels in, respectively, gonads, muscle and muscle plus gonads are below the regulatory limit of 20 mg DA/kg with 99% certainty. Such an analysis was not possible for the other scallop species. In the absence of data from member states, published data of variations between scallops were used to calculate the sample size to ensure a 95% correct prediction on whether the level in scallops in an area or lot is correctly predicted to be compliant/non-compliant. It was shown that 10 scallops per sample would be sufficient to predict with 95% certainty if DA levels in the area/lot were twofold below or above the regulatory limit for the highest reported coefficient of variance (CV) of 1.06. To predict with 95% certainty for levels between 15 and 27 mg DA/kg, a pooled sample of more than 30 scallops would have to be tested., (© 2021 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

DNA/RNA synthesis precursors are especially vulnerable to damage induced by reactive oxygen species occurring following oxidative stress. Guanosine triphosphates are the prevalent oxidized nucleotides, which can be misincorporated during replication, leading to mutations and cell death. Here, we present a novel method based on micro-Raman spectroscopy, combined with ab initio calculations, for the identification, detection, and quantification of oxidized nucleotides at low concentration. We also show that the Raman signature in the terahertz spectral range (<100 cm -1 ) contains information on the intermolecular assembly of guanine in tetrads, which allows us to further boost the oxidative damage detection limit. Eventually, we provide evidence that similar analyses can be carried out on samples in very small volumes at very low concentrations by exploiting the high sensitivity of surface-enhanced Raman scattering combined with properly designed superhydrophobic substrates. These results pave the way for employing such advanced spectroscopic methods for quantitatively sensing the oxidative damage of nucleotides in the cell.

The EFSA Scientific Committee was asked to provide guidance on the most appropriate in vivo tests to follow up on positive in vitro results for aneugenicity, and on the approach to risk assessment for substances that are aneugenic but not clastogenic nor causing gene mutations. The Scientific Committee confirmed that the preferred approach is to perform an in vivo mammalian erythrocyte micronucleus test with a relevant route of administration. If this is positive, it demonstrates that the substance is aneugenic in vivo . A negative result with evidence that the bone marrow is exposed to the test substance supports a conclusion that aneugenic activity is not expressed in vivo . If there is no evidence of exposure to the bone marrow, a negative result is viewed as inconclusive and further studies are required. The liver micronucleus assay, even though not yet fully validated, can provide supporting information for substances that are aneugenic following metabolic activation. The gastrointestinal micronucleus test, conversely, to be further developed, may help to assess aneugenic potential at the initial site of contact for substances that are aneugenic in vitro without metabolic activation. Based on the evidence in relation to mechanisms of aneugenicity, the Scientific Committee concluded that, in principle, health-based guidance values can be established for substances that are aneugenic but not clastogenic nor causing gene mutations, provided that a comprehensive toxicological database is available. For situations in which the toxicological database is not sufficient to establish health-based guidance values, some approaches to risk assessment are proposed. The Scientific Committee recommends further development of the gastrointestinal micronucleus test, and research to improve the understanding of aneugenicity to support risk assessment., (© 2021 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Objective/hypothesis: This study describes a multicentric experience with the use of prelacrimal approach (PLA), focusing on preoperative radiological parameters potentially associated with surgical outcomes and postoperative morbidity., Study Design: Retrospective case-series., Methods: A retrospective review of patients undergoing PLA in three European referral centers was performed. The post-operative morbidity was analyzed in relation to two radiological parameters: width of prelacrimal recess (WPR) and internal angle of pyriform notch (APN)., Results: The study included 28 patients affected by Schneiderian papilloma (20 cases), inflammatory disease (6 cases), schwannoma (1 case), and osteoma (1 case). The most reported sequela was paresthesia of ipsilateral anterior superior alveolar process (25% of the cases). An association between post-operative morbidity and APN was observed (P = .047)., Conclusions: Preoperative radiological evaluation of WPR is crucial in understanding the feasibility of the approach, while APN measurement may predict postoperative morbidity, which is paramount in the patients' counseling., Level of Evidence: 4 case-series Laryngoscope, 131:1715-1721, 2021., (© 2020 American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA).)

In recent decades, the ever-expanding use of endoscopes and development of dedicated instrumentation have reshaped the panorama of surgical approaches to the frontal sinus. 1 Nonetheless, the far lateral portion of the sinus might still represent a concern, especially in cases with unfavorable or distorted anatomy. 2 , 3 We report the case of a 52-year-old man, referred to our department for recurrent episodes of left orbital swelling and supraorbital headache, 3 months after Draf III frontal sinusotomy for marsupialization of multiple frontal mucoceles. Computed tomography and magnetic resonance imaging scans were consistent with persistent inflammatory tissue in the far lateral left frontal sinus. Revision surgery was performed, adopting a combined endonasal orbital transposition 3 and superior eyelid transorbital approach. 4 , 5 The postoperative course was uneventful, and the microbiologic and histologic examinations demonstrated noninvasive Aspergillus fumigatus infection. The radiologic control showed patency of the frontal recess and complete clearance of the sinus. The patient is asymptomatic after 16 months (Video 1). The transorbital approach is effective in managing orbital and frontal sinus diseases, 6 and the combination with the endonasal route grants complete access to the frontal sinus, even in cases of high pneumatization and lateral extension. 4 , 7 Multiportal transorbital approaches represent additional techniques in the rhinologist's surgical armamentarium, which can overcome the limits of a single port approach. 8 , 9 Reports on their use providing technical hints and critical considerations are to be encouraged to ease and stimulate the surgical training in this field., (Copyright © 2021 Elsevier Inc. All rights reserved.)