Evaluation of the efficacy of EU-TIRADS and ACR-TIRADS in risk stratification of pediatric patients with thyroid nodules

BACKGROUND: Pediatric thyroid nodules have a lower prevalence but a higher rate of malignancy (ROM) than those in adults. Ultrasound features suspected of malignancy lead to fine needle aspiration biopsy (FNAB) and subsequent cytological determination, upon which management is decided. Based on the characteristics of ultrasound, to standardize clinician decisions and avoid unnecessary FNAB, the European Thyroid Association and the American Radiology College have established guidelines for Thyroid Imaging, Reporting and Data System (EU-TIRADS and ACR-TIRADS) for ROM stratification of thyroid nodules. The aim of this study is to evaluate the diagnostic performance of ACR-TIRADS and EU-TIRADS in pediatric age. MATERIALS AND METHODS: Subjects younger than 18 years of age with thyroid nodules greater than 0.5 cm observed in the 2000-2020 period were included. RESULTS: Data from 200 subjects were collected. The overall ROM was 13%, rising to 26% if nodules with a diameter >1 cm were considered. Patients with a malignant nodule were more likely to have a higher EU-TIRADS score (p=0.03). Missed cancer diagnoses were 26.9%. Using the EU-TIRADS system, 40% of FNABs could have been avoided, while this scoring system would have resulted in FNAB being performed in 12% of cases where the assessment of ultrasound features would not recommend FNAB. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 73.1%, 57.1%, 73.1%, and 50%, respectively. Even considering the ACR-TIRADS, a higher score correlated with a higher ROM (p<0.001). This system missed 6 diagnoses of cancer (23.1%). Using the ACR-TIRADS system, 45.3% of FNABs could have been avoided, while FNAB should have been performed in 12% of cases where it was not recommended by ultrasound characteristics. Sensitivity, specificity, PPV and NPV were 76.9%, 50%, 76.9%, and 42.9%, respectively. CONCLUSION: The present study confirms the correspondence of the EU-TIRADS and ACR-TIRADS categories with respect to malignancy but indicates not entirely satisfactory performance compared to FNAB alone. However, the use of the two TIRADS systems should be encouraged in multicentre studies to increase their performance and establish paediatric-specific points in the scoring criteria

Il trasporto pubblico locale e la concorrenza. Cambiare paradigma per salvare il servizio: il caso ligure.

Local Public Transportation (LPT) in Italy is usually managed through inhouse companies owned by local governments. In the past few years a wave of reforms has invested the sector, with some regions trying to increase the companies' size. This paper provides an extensive review of the literature, showing that there is little evidence of scale and scope economies beyond a relatively small size. Moreover, there is some evidence that competition in the market, as well as competition for the market, is possible, if the service is fragmented by distinguishing between the "public" service and the potentially profitable part of the service. The paper examines the situation of the Liguria region in Italy, where the regional government is pushing for an integration of the 5 existing companies. The paper argues that an integration is likely to push costs upwards and suggests to privatize the companies, while liberalizing the service, in order to increase the efficiency

SARS-CoV-2 vaccine-related cutaneous manifestations: a systematic review

To date, over 250 million people have been reportedly infected by COVID-19 disease, which has spread across the globe and led to approximately 5.1 million fatalities. To prevent both COVID-19 and viral transmission, DNA-based/RNA-based vaccines, non-replicating viral vector vaccines, and inactivated vaccines have been recently developed. However, a precise clinical and histological characterization of SARS-CoV-2 vaccine-related dermatological manifestations is still lacking. A systematic review of 229 articles was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, in order to provide an extensive overview of SARS-CoV-2 vaccine-related skin manifestations. Data on demographics, number of reported cases with cutaneous involvement, vaccine, and rash type (morphology) were extracted from articles and summarized. A total of 5941 SARS-CoV-2 vaccine-related dermatological manifestations were gathered. Local injection-site reactions were the most frequently observed, followed by rash/unspecified cutaneous eruption, urticarial rashes, angioedema, herpes zoster, morbilliform/maculopapular/erythematous macular eruption, pityriasis rosea and pityriasis rosea-like eruptions, and other less common dermatological manifestations. Flares of pre-existing dermatological conditions were also reported. Cutaneous adverse reactions following SARS-CoV-2 vaccine administration seem to be heterogeneous, rather infrequent, and not life-threatening. Vaccinated patients should be monitored for skin manifestations, and dermatological evaluation should be offered, when needed

In vitro differentiation of human amniotic epithelial cells into insulin-producing 3D spheroids

Regenerative medicine and stem cell therapy may represent the solution for the treatment of non-curable human diseases such as type 1 diabetes. In this context of growing demand for functional and safe stem cells, human amniotic epithelial cells (hAECs) from term placenta have attracted increasing interest for their wide availability, stem cell properties, and differentiation plasticity, which make them a promising tool for stem cell-based therapeutic applications. We initially assayed the stemness characteristics of hAECs in serum-free conditions. Subsequently we developed a culture procedure on extracellular matrix for the formation of three-dimensional (3D) spheroids. Finally, we tested the immunomodulation and differentiation potential of hAEC spheroids: the presence of pancreatic endocrine hormones was revealed with transmission electron microscopy and immunofluorescence analyses; the release of C-peptide in hyperglycemic conditions was assayed with ELISA.The serum-free culture conditions we applied proved to maintain the basic stemness characteristics of hAECs. We also demonstrated that 3D spheroids formed by hAECs in extracellular matrix can be induced to differentiate into insulin-producing cells. Finally, we proved that control and induced cells equally inhibit the proliferation of activated mononuclear cells.The results of this study highlight the properties of amnion derived epithelial cells as promising and abundant source for cell-based therapies. In particular we are the first group to show the in vitro pancreatic induction of hAECs cultured on extracellular matrix in a 3D fashion. We accordingly propose the outcomes of this study as a novel contribution to the development of future cell replacement therapies involving placenta-derived cells

Age-related changes in the matrisome of the mouse skeletal muscle

Aging is characterized by a progressive decline of skeletal muscle (SM) mass and strength which may lead to sarcopenia in older persons. To date, a limited number of studies have been performed in the old SM looking at the whole, complex network of the extracellular matrix (i.e., matrisome) and its aging-associated changes. In this study, skeletal muscle proteins were isolated from whole gastrocnemius muscles of adult (12 mo.) and old (24 mo.) mice using three sequential extractions, each one analyzed by liquid chromatography with tandem mass spectrometry. Muscle sections were investigated using fluorescence- and transmission electron microscopy. This study provided the first characterization of the matrisome in the old SM demonstrating several statistically significantly increased matrisome proteins in the old vs. adult SM. Several proteomic findings were confirmed and expanded by morphological data. The current findings shed new light on the mutually cooperative interplay between cells and the extracellular environment in the aging SM. These data open the door for a better understanding of the mechanisms modulating myocellular behavior in aging (e.g., by altering mechano-sensing stimuli as well as signaling pathways) and their contribution to age-dependent muscle dysfunction

Extensive "halo naevi" phenomenon and regression of melanin during nivolumab treatment in metastatic melanoma: A predictor of a better outcome?

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Current Controversies and Challenges on BRAF V600K-Mutant Cutaneous Melanoma

About 50% of melanomas harbour a BRAF mutation. Of these 50%, 10% have a V600K mutation. Although it is the second most common driver mutation after V600E, no specific studies have been conducted to identify a clinical and therapeutic gold standard for this patient subgroup. We analysed articles, including registrative clinical trials, to identify common clinical and biological traits of the V600K melanoma population, including different adopted therapeutic strategies. Melanoma V600K seems to be more frequent in Caucasian, male and elderly populations with a history of chronic sun damage and exposure. Prognosis is poor and no specific prognostic factor has been identified. Recent findings have underlined how melanoma V600K seems to be less dependent on the ERK/MAPK pathway, with a higher expression of PI3KB and a strong inhibition of multiple antiapoptotic pathways. Both target therapy with BRAF inhibitors + MEK inhibitors and immunotherapy with anti-checkpoint blockades are effective in melanoma V600K, although no sufficient evidence can currently support a formal recommendation for first line treatment choice in IIIC unresectable/IV stage patients. Still, melanoma V600K represents an unmet medical need and a marker of poor prognosis for cutaneous melanoma

Antitumor immunization of mothers delays tumor development in cancer-prone offspring

Maternal immunization is successfully applied against some life-threatening infectious diseases as it can protect the mother and her offspring through the passive transfer of maternal antibodies. Here, we sought to evaluate whether the concept of maternal immunization could also be applied to cancer immune-prevention. We have previously shown that antibodies induced by DNA vaccination against rat Her2 (neu) protect heterozygous neu-transgenic female (BALB-neuT) mice from autochthonous mammary tumor development. We, herein, seek to evaluate whether a similar maternal immunization can confer antitumor protection to BALB-neuT offspring. Significantly extended tumor-free survival was observed in BALB-neuT offspring born and fed by mothers vaccinated against neu, as compared to controls. Maternally derived anti-neu immunoglobulin G (IgG) was successfully transferred from mothers to newborns and was responsible for the protective effect. Vaccinated mothers and offspring also developed active immunity against neu as revealed by the presence of T–cell-mediated cytotoxicity against the neu immunodominant peptide. This active response was due to the milk transfer of immune complexes that were formed between the neu extracellular domain, shed from vaccine-transfected muscle cells, and the anti-neu IgG induced by the vaccine. These findings show that maternal immunization has the potential to hamper mammary cancer in genetically predestinated offspring and to develop into applications against lethal neonatal cancer diseases for which therapeutic options are currently unavailable

Aged gastrocnemius muscle of mice positively responds to a late onset adapted physical training

Introduction: A regular physical training is known to contribute to preserve muscle mass and strength, maintaining structure and function of neural and vascular compartments and preventing muscle insulin resistance and inflammation. However, physical activity is progressively reduced during aging causing mobility limitations and poor quality of life. Although physical exercise for rehabilitation purposes (e.g., after fractures or cardiovascular events) or simply aiming to counteract the development of sarcopenia is frequently advised by physicians, nevertheless few data are available on the targets and the global effects on the muscle organ of adapted exercise especially if started at old age.Methods: To contribute answering this question for medical translational purposes, the proteomic profile of the gastrocnemius muscle was analyzed in 24-month-old mice undergoing adapted physical training on a treadmill for 12 weeks or kept under a sedentary lifestyle condition. Proteomic data were implemented by morphological and morphometrical ultrastructural evaluations.Results and Discussion: Data demonstrate that muscles can respond to adapted physical training started at old age, positively modulating their morphology and the proteomic profile fostering protective and saving mechanisms either involving the extracellular compartment as well as muscle cell components and pathways (i.e., mitochondrial processes, cytoplasmic translation pathways, chaperone-dependent protein refolding, regulation of skeletal muscle contraction). Therefore, this study provides important insights on the targets of adapted physical training, which can be regarded as suitable benchmarks for future in vivo studies further exploring the effects of this type of physical activity by functional/metabolic approaches