Multimodality treatment of malignant pleural mesothelioma with or without immunotherapy: does it change anything?☆

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Differential modulation by vanadium pentoxide of the secretion of CXCL8 and CXCL11 chemokines in thyroid cells

Recently it has been hypothesized that vanadium serves a carcinogenic role in the thyroid. However, to date, no in vivo or in vitro studies have evaluated thyroid disruption in humans and/or animals following exposure to vanadium. The present study evaluated the effect of vanadium pentoxide (V2O5) on cell viability and proliferation, and chemokine (C-X-C motif) ligand (CXCL)8 and CXCL11 secretion in normal thyrocytes. The results demonstrated that V2O5had no effect on thyroid follicular cell viability and proliferation. However, V2O5was able to induce the secretion of CXCL8 and CXCL11 chemokines from thyrocytes. Notably, V2O5synergistically increased the effect of the interferon (IFN)-γ on CXCL11 secretion. In addition, V2O5synergistically increased the effect of tumor necrosis factor-alpha; on CXCL8 secretion, and abolished the inhibitory effect of IFN-γ. Overall this induction of CXCL8 and CXCL11 secretion may lead to the induction and perpetuation of an inflammatory reaction in the thyroid. Further studies are now required to evaluate thyroid function and nodule development in subjects who are occupationally exposed, or living in polluted areas

Multidisciplinary Management of Spondyloarthritis-Related Immune-Mediated Inflammatory Disease

Immune-mediated inflammatory diseases (IMIDs) are chronic autoimmune conditions that share common pathophysiologic mechanisms. The optimal management of patients with IMIDs remains challenging because the coexistence of different conditions requires the intervention of several specialists. The aim of this study was to develop a series of statements defining overarching principles that guide the implementation of a multidisciplinary approach for the management of spondyloarthritis (SpA)-related IMIDs including SpA, psoriasis, psoriatic arthritis, Crohn's disease, ulcerative colitis and uveitis

Il progetto Marel: dalla costituzione della rete di ambulatori di Medicina del Lavoro all’analisi dei dati raccolti sulle esposizioni professionali

Il progetto Marel (MAlattie e Rischi Emergenti sul Lavoro) prevede tra le finalità principali la raccolta di informazioni circa le esposizioni professionali relative a malattie di possibile origine lavorativa. Per raggiungere tale obiettivo si è costituita una rete di ambulatori specialistici di Medicina del Lavoro. I dati sulle esposizioni professionali costituiscono l’informazione chiave del sistema Marel, con dettagli che consentono analisi relative ai settori di attività lavorativa e all’anamnesi professionale. I dati raccolti nella fase sperimentale fanno riferimento a 843 lavoratori sottoposti a visita presso cinque ambulatori. Le donne sono in media il 25% del totale, ed hanno un’età media più bassa rispetto agli uomini, rispettivamente di 53 e 59 anni. Ogni lavoratore visitato riporta in media due malattie. Tra le malattie riferite, “Altri disturbi dei dischi intervertebrali” era il gruppo di patologie più rappresentato (12,3% del totale). La raccolta omogenea e sistematica di informazioni provenienti da più centri specialistici può produrre un insieme di notizie di grande utilità a fini di conoscenza e di prevenzione, poiché permette di considerare anche casi di patologie che, per la loro natura o per il loro particolare rapporto con misconosciuti fattori di rischio professionale, non risultano essere ancora considerate come malattie correlate al lavoro

Effects of Sub-Acute Exposure to Rhodium (as Rh (III) chloride hydrate) on Cytokines in Female Wistar Rats

Quantitative changes in different cytokines were determined in serum of female Wistar rats exposed to Rhodium (III) chloride hydrate to evaluate its early effects on the immune system. Findings revealed an inhibitory effect of Rh salt since each cytokine, with the exceptions of IL-1\u3b1 and IL-2 levels observed at the highest doses of exposure, was reduced compared to the controls and interestingly, the lowest doses induced the greatest inhibition. This generalized decrease of cytokine levels was not related to a specific cytokine pathway, and may suggest an anti-inflammatory role of Rh salt

Primary cell cultures for the personalized therapy in aggressive thyroid cancer of follicular origin

Thyroid cancer (TC) is the most prevalent endocrine malignancy. More than 90% of TC is represented by differentiated TC (DTC) arising from the follicular thyroid cells. DTC includes papillary TC (PTC), follicular TC (FTC), and Hürthle cell TC. Anaplastic TC (ATC) accounts for 1% of TC, and it represents 15-40% of TC death. Current treatment strategies are not completely effective against aggressive DTC or ATC, and mortality is one of the most important challenges. Recently, progresses have been obtained in the understanding of the molecular/genetic basis of TC progression, and new drugs have been introduced [i.e. tyrosine kinase inhibitors (TKIs)], able to block the oncogenic or signaling kinases, associated with cellular growth. Thyroid cell lines, obtained from tumoral cells and chosen for high proliferation in vitro, have been used as preclinical models. Actually, these cells lose the characteristic features of the primary tumor, because they adapt to in vitro growth conditions. For these reasons, the use of these cell lines has important limitations, and more recently human primary cell cultures have been established as monolayer cultures, and investigated for their biological behavior. Moreover, in the past, primary TC cells could be collected only through surgical biopsies, while recently human primary cell cultures can be established also from samples of fine-needle aspiration citology from aggressive dedifferentiated DTC or ATC. Testing in vitro different TKIs in each patient can help to develop new personalized treatments, without using ineffective drugs. In conclusion, personalized medicine and precise oncology, which consider both patients and their disease features, represent the future of the treatment approach, and further progress is needed in this direction

Neoadjuvant radiotherapy dose escalation for locally advanced rectal cancers in the new era of radiotherapy: A review of literature

BACKGROUND The standard treatment of locally advanced rectal cancers (LARC) consists on neoadjuvant chemoradiotherapy followed by total mesorectal excision. Different data in literature showed a benefit on tumor downstaging and pathological complete response (pCR) rate using radiotherapy dose escalation, however there is shortage of studies regarding dose escalation using the innovative techniques for LARC (T3-4 or N1-2). AIM To analyze the role of neoadjuvant radiotherapy dose escalation for LARC using innovative radiotherapy techniques. METHODS In December 2020, we conducted a comprehensive literature search of the following electronic databases: PubMed, Web of Science, Scopus and Cochrane library. The limit period of research included articles published from January 2009 to December 2020. Screening by title and abstract was carried out to identify only studies using radiation doses equivalent dose 2 Gy fraction (EQD2) ≥ 54 Gy and Volumetric Modulated Arc Therapy (VMAT), intensity-modulated radiotherapy or image-guided radiotherapy (IGRT) techniques. The authors’ searches generated a total of 2287 results and, according to PRISMA Group (2009) screening process, 21 publications fulfil selection criteria and were included for the review. RESULTS The main radiotherapy technique used consisted in VMAT and IGRT modality. The mainly dose prescription was 55 Gy to high risk volume and 45 Gy as prophylactic volume in 25 fractions given with simultaneous integrated boosts technique (42.85%). The mean pCR was 28.2% with no correlation between dose prescribed and response rates (P value ≥ 0.5). The R0 margins and sphincter preservation rates were 98.88% and 76.03%, respectively. After a mean follow-up of 35 months local control was 92.29%. G3 or higher toxicity was 11.06% with no correlation between dose prescription and toxicities. Patients receiving EQD2 dose > 58.9 Gy and BED > 70.7 Gy had higher surgical complications rates compared to other group (P value = 0.047). CONCLUSION Dose escalation neoadjuvant radiotherapy using innovative techniques is safe for LARC achieving higher rates of pCR. EQD2 doses > 58.9 Gy is associated with higher rate of surgical complications

Cerebral neoplastic enhancing lesions: Multicenter, randomized, crossover intraindividual comparison between gadobutrol (1.0M) and gadoterate meglumine (0.5M) at 0.1mmolGd/kg body weight in a clinical setting

OBJECTIVE: Two macrocyclic extracellular contrast agents, one-molar neutral gadobutrol and ionic gadoterate meglumine, were compared to determine the overall preference for one or the other in a clinical setting. MATERIALS AND METHODS: Multicenter, randomized, single-blind, intra-individually controlled, comparison study with a corresponding blinded read. Efficacy analysis was based on 136 patients who underwent identical MRI examinations: group A first received 1.0M gadobutrol followed by 0.5M gadoterate meglumine 48 h to 7 days later; group B had a reversed administration order. Three independent blinded readers assessed off-site their overall diagnostic preference (primary efficacy parameter) based on a matched pairs approach. RESULTS: Superiority of gadobutrol over gadoterate meglumine was demonstrated for the qualitative assessment of overall preference across all readers by a statistically significant difference between both contrast agents for this primary endpoint. Preferences in lesion enhancement (secondary endpoint) were also found significantly in favor of gadobutrol. For preference in lesion delineation from surrounding tissue/edema and for internal structure only a trend towards a higher proportion for gadobutrol was found (except for internal structure reported by one reader, which showed a result of statistical significance). Lesion contrast and relative lesion enhancement (quantitative parameters) were statistically significantly higher for gadobutrol compared to gadoterate meglumine. CONCLUSION: Contrast-enhanced MRI of neoplastic brain lesions at a dose of 0.1 mmol Gd/kg body weight, assessed in a standardized off-site blinded reading, results in a significantly higher qualitative and quantitative preference for gadobutrol compared to gadoterate meglumine