Lenvatinib treatment for thyroid cancer in COVID era: safety in a patient with lung metastases and SARS-CoV-2 infection.

During the coronavirus disease 2019 (COVID-19) pandemic, clinicians are required to manage patient care for pre-existing conditions. Currently, there are no clear indications regarding the management of lenvatinib-treated patients for radioiodine-refractory thyroid cancer and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A 74-year-old male patient was treated with lenvatinib since March 2019, with disease recurrence in the thyroid bed and bilateral multiple lung metastases. The patient partially responded to treatment, with reduction in lung metastases. In September 2019, the patient tested positive for SARS-CoV-2 and isolated at home. Initially asymptomatic, the patient developed mild symptoms. Lenvatinib treatment continued with daily monitoring of vital signs. After telemedicine consultation of patient's clinical condition, severity of symptoms was low. He tested negative for SARS-CoV-2 21 days after testing positive. The patient received the full course of lenvatinib treatment. This is the first reported case of a lenvatinib-treated patient who developed COVID-19 and could continue treatment. Despite concerns over COVID-19, clinicians should not overlook treatment of pre-existing diseases or discontinue treatment, particularly for cancer. Clinicians should evaluate a patient's history and clinical presentation, monitoring the patient to reduce the development of complications in high-risk settings, avoiding treatment discontinuation.

Anisakiasis: The Importance of Prevention and the Role of Diet Therapy in Allergic Patients.

INTRODUCTION: Anisakiasis is a zoonosis of parasitic origin whose diffusion seems to be continuously increasing. OBJECTIVE: The aim of this study was to evaluate the benefits of a fish-free diet in patients allergic to Anisakis simplex as well as underlining the importance of awareness and prevention. Furthermore, we aimed to investigate the critical issues related to the spread of anisakiasis in relation to eating habits. METHODS: Patients were assessed by means of skin prick tests (SPTs) and targeted laboratory testing, with an 18-month-long fish-free diet being recommended in cases of severe sensitization. The degree of awareness about anisakiasis was evaluated from interviews. Patients were subjected to follow-up visits after 18 months. RESULTS: A total of 70 cases of sensitization to A. simplex were evaluated. The Interview answers highlighted a general state of misinformation among patients and healthy subjects along with a remarkable underestimation of anisakiasis-related risks. An overall lack of care regarding eating habits and diet plans also emerged. In 21 patients affected by severe sensitization, clinical and laboratory evaluations were repeated after 18 months of the subjects being on a fish-free diet. There was a remarkable improvement in serum IgE levels and clinical symptoms. CONCLUSION: Data analysis proved the need to implement new and more effective awareness-raising and prevention campaigns in order to reduce the incidence of anisakiasis. It is crucial to establish an adequate diet therapy for sensitized patients. Evaluation of cytokine patterns suggests how a polyphenol-rich regime can activate regulatory T cell function and possibly reduce the allergic and inflammatory components of the disease.

The Interplay between Immune System and Microbiota in Osteoporosis.

Osteoporosis is a disease characterized by low bone mass and alterations of bone microarchitecture, with an increased risk of fractures. It is a multifactorial disorder that is more frequent in postmenopausal women but can be associated to other diseases (inflammatory and metabolic diseases). At present, several options are available to treat osteoporosis trying to block bone reabsorption and reduce the risk of fracture. Anyway, these drugs have safety and tolerance problems in long-term treatment. Recently, gut microbiota has been highlighted to have strong influence on bone metabolism, becoming a potential new target to modify bone mineral density. Such evidences are mainly based on mouse models, showing an involvement in modulating the interaction between the immune system and bone cells. Germ-free mice represent a basic model to understand the interaction between microbiota, immune system, and bone cells, even though data are controversial. Anyway, such models have unequivocally demonstrated a connection between such systems, even if the mechanism is unclear. Gut microbiota is a complex system that influences calcium and vitamin D absorption and modulates gut permeability, hormonal secretion, and immune response. A key role is played by the T helper 17 lymphocytes, TNF, interleukin 17, and RANK ligand system. Other important pathways include NOD1, NOD2, and Toll-like receptor 5. Prebiotics and probiotics are a wide range of substances and germs that can influence and modify microbiota. Several studies demonstrated actions by different prebiotics and probiotics in different animals, differing according to sex, age, and hormonal status. Data on the effects on humans are poor and controversial. Gut microbiota manipulation appears a possible strategy to prevent and treat osteopenia and/or osteoporosis as well as other possible bone alterations, even though further clinical studies are necessary to identify correct procedures in humans.

A Reappraisal of Suspicious Sonographic Features of Thyroid Nodules: Shape Is Not an Independent Predictor of Malignancy.

CONTEXT: For the correct clinical application of the sonographic risk-stratification systems, the definition of independent risk features that are foundational to each system is crucial. OBJECTIVE: The aim of this study was to identify the gray-scale sonographic features independently associated with malignancy, and to compare different definitions. METHODS: This prospective, diagnostic accuracy study took place in a single thyroid nodule referral center. All patients consecutively referred to our center for fine-needle aspiration cytology of a thyroid nodule between November 1, 2015 and March 30, 2020, were enrolled before cytology. Each nodule was examined by 2 experienced clinicians to record the sonographic features on a rating form. Histologic (when available) or cytologic diagnosis was used as the reference standard. For each single sonographic feature and definition, the sensitivity, specificity, positive and negative predictive values, and diagnostic odds ratios (DOR) were calculated. The significant predictors were then included in a multivariable regression model. RESULTS: The final study cohort consisted of 903 nodules in 852 patients. A total of 76 nodules (8.4%) were malignant. Six features were independent predictors of malignancy: suspicious lymph node (DOR 16.23), extrathyroidal extension (DOR 6.60), irregular or infiltrative margins (DOR 7.13), marked hypoechogenicity (DOR 3.16), solid composition (DOR 3.61), and punctate hyperechoic foci (including microcalcifications and indeterminate foci; DOI 2.69). Taller-than-wide shape was not confirmed as an independent predictor. CONCLUSION: We identified the key suspicious features of thyroid nodules and provided a simplified definition of some debated ones. Malignancy rate increases with number of features.

Preoperative Ultrasonography in the Evaluation of Suspected Familial Non-Medullary Thyroid Cancer: Are We Able to Predict Multifocality and Extrathyroidal Extension?

Family history of thyroid cancer increases the risk of harboring thyroid malignancies that end up having extrathyroidal extension (ETE) and multifocality on histology; some authors suggest a more aggressive surgical approach. Their pre-operative identification could allow more conservative surgical procedures if none of these features are suspected. Our aim was to assess if neck ultrasonography could identify or exclude multifocality or ETE in these patients to tailor the extent of surgery. This retrospective study included patients with previous thyroid surgery, ≥1 first-grade relative with thyroid cancer, and who had undergone pre-surgical ultrasound. ETE was suspected in the case of thyroid border interruption or gross invasion of perithyroidal tissues. Multiple suspicious nodules were defined as suspicion of multifocal cancer. The cohort consisted of 45 patients (median age 49 years, 40 with thyroid cancer, 30 females). The positive predictive value of ultrasonography in predicting multifocality and ETE was 57.14% (25.25-84.03) and 41.67% (21.5-65.1%), respectively, while the negative predictive values were 63.2% (56.4-69.4%) and 72.7% (63.3-80.5%). Pre-operative ultrasound examination is unable to reliably identify or exclude multifocal disease or extrathyroidal extension. In patients scheduled for surgery and with a first-degree relative affected by DTC, a "negative" pre-operative US report does not exclude the potential finding of multifocality and ETE at final histopathology.

Lenvatinib for thyroid cancer treatment: discovery, pre-clinical development and clinical application.

Introduction: About one third of patients affected with thyroid cancer present with recurrent disease. Unresectability, advanced disease and radioiodine refractoriness are considered poor prognostic factors. Treatment with small molecules inhibiting molecular signaling can be considered for patients with progressive disease, when other therapeutic strategies cannot be applied. Lenvatinib is a tyrosine kinase inhibitor targeting multiple molecular factors involved in angiogenesis and tumor progression. Preclinical studies have demonstrated the utility of lenvatinib as a targeted therapy for different tumors, including both differentiated and anaplastic thyroid cancer.Areas covered: The authors provide an overview of the preclinical development of lenvatinib in the treatment of thyroid cancer and review its clinical application. They also provide their expert opinion on its development.Expert opinion: Preclinical studies have helped in the understanding of the mechanisms of thyroid carcinogenesis and in the development of a targeted therapy. These findings have represented the rationale for the use of lenvatinib in clinical trials, which have confirmed its utility but yet failed to prove a clear benefit in overall survival. The decision to start a systemic treatment with lenvatinib must be personalized for each patient evaluating the risk/benefits ratio. Treatment emergent adverse events must be considered and reasonably managed by a multidisciplinary approach.

Peer review of the pesticide risk assessment of the active substance lavandulylsenecioate.

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State Italy for the pesticide active substance lavandulylsenecioateare reported. The context of the peer review was that required by Regulation (EC) No 1107/2009 of the European Parliament and of the Council.The conclusions were reached on the basis of the evaluation of the representative uses evaluated as a pheromone comprising manual applications to control Planococcusficus (vine mealybug) populations by mating disruption in table grape, wine grape, raisins and any other crops where P. ficus may be a pest in Southern Europe. The reliable endpoints,appropriate for use in regulatory risk assessmentare presented. Missing information identified as being required by the regulatory framework is listed.Concerns are identified.

Peer review of the pesticide risk assessment of the active substance mancozeb.

The conclusions of EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State the United Kingdom and co-rapporteur Member State Greece for the pesticide active substance mancozeb are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012. The conclusions were reached on the basis of the evaluation of the representative uses of mancozeb as a fungicide on wheat (winter/spring), grapevine, potatoes and tomatoes. The reliable end points, appropriate for use in regulatory risk assessment are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are identified.

Peer review of the pesticide risk assessment of the active substance fenamiphos.

The conclusions of EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State Greece and co-rapporteur Member State Cyprus for the pesticide active substance fenamiphos are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012. The conclusions were reached on the basis of the evaluation of the representative uses of fenamiphos as a nematicide in fruiting vegetables (i.e. tomato, aubergine, cucumber, pepper and courgette), herbaceous ornamentals and in nursery stock (both perennial and herbaceous species). The reliable end points, appropriate for use in regulatory risk assessment are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are identified.

Peer review of the pesticide risk assessment of the active substance Verticillium albo-atrum strain WCS850.

The conclusions of EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State Sweden and co-rapporteur Member State the Netherlands for the pesticide active substance Verticillium albo-atrum strain WCS850 are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012. The conclusions were reached on the basis of the evaluation of the representative use of Verticillium albo-atrum strain WCS850 as a fungicide on elm trees. The reliable end points, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed.

Peer review of the pesticide risk assessment of the active substance thiacloprid.

The conclusions of EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State the United Kingdom and co-rapporteur Member State Germany for the pesticide active substance thiacloprid are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012. The conclusions were reached on the basis of the evaluation of the representative uses of thiacloprid as an insecticide on oilseed rape foliar use and maize seed treatment. The peer review also provided conclusions on whether exposure of humans to thiacoprid can be considered negligible, taking into account the European Commission's draft guidance on this topic. Confirmatory data following the review of existing maximum residue levels (MRLs) according to Article 12 of Regulation (EC) No 396/2005 were also assessed in this conclusion. The reliable end points, appropriate for use in regulatory risk assessment are presented. An evaluation of data concerning the necessity of thiacloprid as an insecticide to control a serious danger to plant health which cannot be contained by other available means, including non-chemical methods is presented. Missing information identified as being required by the regulatory framework is listed. Concerns are identified.

Peer review of the pesticide risk assessment of the active substance pyriproxyfen.

The conclusions of EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State the Netherlands and co-rapporteur Member State Spain for the pesticide active substance pyriproxyfen and the assessment of applications for maximum residue levels (MRLs) are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012. The conclusions were reached on the basis of the evaluation of the representative uses of pyriproxyfen as an insecticide on citrus fruit, pome fruit (apple, pears), tomatoes, ornamentals (field use) and tomatoes, ornamentals (greenhouse application). MRLs were assessed in citrus fruits. The reliable end points, appropriate for use in regulatory risk assessment and the proposed MRLs, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are identified.

Updated peer review of the pesticide risk assessment for the active substance terbuthylazine in light of confirmatory data submitted.

The conclusions of EFSA following the peer review of the initial risk assessment carried out by the competent authority of the rapporteur Member State, the United Kingdom, for the pesticide active substance terbuthylazine are reported. The context of the peer review was that requested by the European Commission following the submission and evaluation of confirmatory data on groundwater metabolites. The conclusions were reached on the basis of the evaluation of the representative uses of terbuthylazine as a herbicide on maize and sorghum and taking into account the scientific opinion of the EFSA Panel on Plant Protection Products and their Residues (PPR) on the setting of health-based reference values for metabolites of the active substance terbuthylazine. The reliable endpoints concluded as being appropriate for use in regulatory risk assessment, derived from the available studies and literature in the dossier peer reviewed, are presented. Concerns are identified.