Genetic models of osteochondroma onset and neoplastic progression: evidence for mechanisms alternative to EXT genes inactivation

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Liquid biopsy is a promising tool for genetic testing in idiopathic pulmonary fibrosis

Liquid biopsy, which allows the isolation of circulating cell-free (ccf) DNA from blood, is an emerging noninvasive tool widely used in oncology for diagnostic and prognosis purposes. Previous data have shown that serum cfDNA discriminates idiopathic pulmonary fibrosis (IPF) from other interstitial lung diseases. Our study aimed to measure plasma levels of ccfDNA in 59 consecutive therapy-naive and clinically stable IPF patients. The single nucleotide polymorphism (SNP) of the MUC5B gene promoter (rs35705950), associated with increased susceptibility of developing IPF, has been sought in plasma cfDNA and genomic DNA for comparison. Thirty-five age-and sex-matched healthy volunteers were recruited as the control group. Our results show that concentrations of small-size ccfDNA fragments were significantly higher in IPF patients than in controls and inversely correlated with lung function deterioration. Moreover, the median level of 104 ng/mL allowed discriminating patients with mild disease from those more advanced. The rs35705950 polymorphism was found in 11.8% of IPF patients and 8% of controls, with no differences. Complete concordance between ccfDNA and genomic DNA was detected in all control samples, while four out of seven IPF cases (57%) carrying the rs35705950 polymorphism were discordant from genomic DNA (7% of total IPF). Liquid biopsy is a suitable tool with optimistic expectations of application in the field of IPF. In analogy with cancer biology, finding some discrepancies between ccfDNA and genomic DNA in IPF patients suggests that the former may convey specific genetic information present in the primary site of the disease

Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study

Background: Hydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19. Objective: We set-up a multicenter Italian collaboration to investigate the relationship between HCQ therapy and COVID-19 in-hospital mortality. Methods: In a retrospective observational study, 3,451 unselected patients hospitalized in 33 clinical centers in Italy, from February 19, 2020 to May 23, 2020, with laboratory-confirmed SARS-CoV-2 infection, were analyzed. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received HCQ with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores, with the addition of subgroup analyses. Results: Out of 3,451 COVID-19 patients, 76.3% received HCQ. Death rates (per 1,000 person-days) for patients receiving or not HCQ were 8.9 and 15.7, respectively. After adjustment for propensity scores, we found 30% lower risk of death in patients receiving HCQ (HR=0.70; 95%CI: 0.59 to 0.84; E-value=1.67). Secondary analyses yielded similar results. The inverse association of HCQ with inpatient mortality was particularly evident in patients having elevated C-reactive protein at entry. Conclusions: HCQ use was associated with a 30% lower risk of death in COVID-19 hospitalized patients. Within the limits of an observational study and awaiting results from randomized controlled trials, these data do not discourage the use of HCQ in inpatients with COVID-19

KRAS mutations testing in non-small cell lung cancer: The role of Liquid biopsy in the basal setting

In advanced stage non-small cell lung cancer (NSCLC) patients, Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) testing may soon acquire a predictive significance to select patients for AMG510 treatment. Since tissue samples are not always available, liquid biopsy may represent a viable option for KRAS testing. Here, we review the last three years clinical practice performed on 194 plasma based liquid biopsies by next generation sequencing (NGS) SiRe® panel. In particular, 36 (18.6%) KRAS mutated cases were identified, with an overall median allelic frequency of 5.0% (ranging between 0.2% and 46.8%). No concomitant mutations were observed in the other NSCLC clinical relevant genes included in the SiRe® panel, such as epidermal growth factor receptor (EGFR) and v-Raf murine sarcoma viral oncogene homolog B (BRAF). Exon 2 p.G12C was the most common detected mutation (13/36, 36.1%). In conclusion, our data update and confirm that SiRe® NGS panel represents a robust analytical tool to assess KRAS mutational status on circulating tumor DNA. Further investigation is required to design more cost-effective diagnostic algorithms to harmonize clinical relevant biomarker testing on tissue and blood in advanced stage NSCLC clinical practice

Exercise induced changes in salivary and serum metabolome in trained standardbred, assessed by 1H-NMR

In the present study, data related to the metabolomics of saliva and serum in trained standardbred horses are provided for the first time. Metabolomic analysis allows to analyze all the metabolites within selected biofluids, providing a better understanding of biochemistry modifications related to exercise. On the basis of the current advances observed in metabolomic research on human athletes, we aimed to investigate the metabolites\u2019 profile of serum and saliva samples collected from healthy standardbred horses and the relationship with physical exercise. Twelve trained standardbred horses were sampled for blood and saliva before (T0) and immediately after (T1) standardized exercise. Metabolomic analysis of both samples was performed by1H-NMR spectroscopy. Forty-six metabolites in serum and 62 metabolites in saliva were detected, including alcohols, amino acids, organic acids, carbohydrates and purine derivatives. Twenty-six and 14 metabolites resulted to be significantly changed between T0 and T1 in serum and saliva, respectively. The findings of 2-hydroxyisobutyrate and 3-hydroxybutyrate in serum and GABA in equine saliva, as well as their modifications following exercise, provide new insights about the physiology of exercise in athletic horses. Glycerol might represent a novel biomarker for fitness evaluation in sport horses

Morphological and Molecular Characterization of Larval and Adult Stages of Eustrongylides excisus (Nematoda: Dioctophymatoidea) with Histopathological Observations

The genus Eustrongylides includes nematodes known as the etiological agent of the \u2018\u2018big red worm disease.\u2019\u2019 The aim of this work was to identify Eustrongylides spp. larvae from fish and adults from great cormorant (Phalacrocorax carbo) sampled at Lake Trasimeno, Italy, by morphological and molecular analysis. Histopathological description of the lesions in birds was also provided. We described adults of Eustrongylides excisus for the first time in Italy, and we also linked larval stages 3 and 4 to adults. The use of molecular tools combined with the traditional taxonomy will help the identification of the species, including species inquirendae. Moreover, molecular analysis can also help to investigate the role of intermediate and paratenic hosts, to deepen the knowledge about geographical distribution of the different Eustrongylides spp. and to define the zoonotic potential of E. excisus, which has not yet been identified as causal agent of human cases

INFESTAZIONE DA NEMATODI IN ESEMPLARI DI CORMORANO COMUNE (PHALACROCORAX CARBO) DEL CENTRO E NORD ITALIA

Negli ultimi anni \ue8 stata segnalata la presenza di stadi larvali di nematodi appartenenti al genere Eustrongylides (Nematoda, Dioctophymatidae) in specie ittiche del Lago Trasimeno (Dezfuli, 2015; Agnetti et al., 2016; Branciari et al., 2016). Il ciclo biologico di questi parassiti sembra prevedere come primi ospiti intermedi anellidi oligocheti, riconoscendo come secondo ospite intermedio numerose specie ittiche e come ospite definitivo gli uccelli ittiofagi. In particolare, il cormorano comune (Phalacrocorax carbo) \ue8 descritto come uno degli ospiti definitivi di Eustrongylides spp., che, localizzandosi nella parete del proventricolo, causa la cosiddetta \u201cBig Red Worm Disease\u201d, responsabile di grave mortalit\ue0 soprattutto in nidiacei (Spalding et al., 2008). In Europa, P. carbo \ue8 una specie tipica delle regioni settentrionali, mentre nell\u2019area mediterranea \ue8 presente perlopi\uf9 come uccello svernante, sia in acque costiere che in bacini interni. La sua dieta \ue8 costituita da almeno 77 specie ittiche (Carss et al., 2003), fra cui Perca fluviatilis, Micropterus salmoides e Atherina boyeri, nelle quali \ue8 stata recentemente dimostrata la presenza di Eustrongylides sp. in Italia. Scopo dell\u2019indagine \ue8 stato quello di definire il grado di infestazione da parassiti di origine ittica in proventricoli di cormorani comuni di due diverse aree, quella del lago Trasimeno (Umbria) e quella comprendente allevamenti ittici e fiumi della provincia di Cuneo (Piemonte), valutando in particolare l\u2019eventuale presenza del nematode Eustrongylides sp. e/o di altri elminti potenzialmente zoonotici. Ventisette soggetti (3 dell\u2019area umbra e 24 dell\u2019area piemontese), morti per cause di natura diversa, sono stati sottoposti ad esame necroscopico, con particolare riferimento al proventricolo; i nematodi isolati sono stati puliti in soluzione fisiologica, contati e conservati in etanolo al 70% per la successiva identificazione morfologica e molecolare. Sia negli esemplari umbri che in quelli piemontesi parassitati il grado di infestazione riscontrato \ue8 stato sovrapponibile, con una media di 9 elminti per stomaco esaminato. Dei 24 campioni piemontesi, 7 hanno mostrato presenza di nematodi nel proventricolo, identificati come Contracaecum rudolphii, parassita gi\ue0 descritto in Italia. Dei 2 soggetti umbri, solo uno ha mostrato presenza di nematodi nel proventricolo, identificati come Eustrongylides sp. I dati preliminari ottenuti avvalorano la presenza di Eustrongylides sp. nel Trasimeno, suggerendo che tale lago rappresenti un habitat ideale per il completamento del ciclo biologico di questo elminta. Ulteriori indagini verranno condotte aumentando la numerosit\ue0 campionaria dei potenziali ospiti ed i siti di campionamento al fine di chiarire l\u2019epidemiologia e la biologia di Eustrongylides sp. sul territorio nazionale

Thyroid fine-needle aspiration trends before, during, and after the lockdown: what we have learned so far from the COVID-19 pandemic

Purpose Nowadays, the clinical management of thyroid nodules needs to be multi-disciplinary. In particular, the crosstalk between endocrinologists and cytopathologists is key. When FNAs are properly requested by endocrinologists for nodules characterised by relevant clinical and ultrasound features, cytopathologists play a pivotal role in the diagnostic work-up. Conversely, improper FNA requests can lead to questionable diagnostic efficiency. Recently, recommendations to delay all non-urgent diagnostic procedures, such as thyroid FNAs, to contain the spread of COVID-19 infection, have made the interplay between endocrinologists and cytopathologists even more essential. The objective of this study was to assess the impact of COVID-19 pandemic on our practice by evaluating the total number of FNAs performed and the distribution of the Bethesda Categories before, during, and after the lockdown. Methods We analysed the FNA trends before (1st January 2019 to March 13th 2020), during (March 14th to May 15th), and after (May 16th to July 7th) the lockdown. Results Although the total number of weekly FNAs dropped from 62.1 to 23.1, our referring endocrinologists managed to prioritise patients with high-risk nodules. In fact, in the post-lockdown, the weekly proportion of benign diagnoses dropped on average by 12% and that of high-risk diagnoses increased by 6%. Conclusions The lesson we have learned so far from this pandemic is that by applying safety protocols to avoid contagion and by increasing the threshold for FNA requests for thyroid nodules, we can continue to guarantee our services to high-risk patients even in times of a health crisis