Increased HMGB1 expression and release by mononuclear cells following surgical/anesthesia trauma

Introduction: High mobility group box 1 (HMGB1) is a key mediator of inflammation that is actively secreted by macrophages and/or passively released from damaged cells. The proinflammatory role of HMGB1 has been demonstrated in both animal models and humans, since the severity of inflammatory response is strictly related to serum HMGB1 levels in patients suffering from traumatic insult, including operative trauma. This study was undertaken to investigate HMGB1 production kinetics in patients undergoing major elective surgery and to address how circulating mononuclear cells are implicated in this setting. Moreover, we explored the possible relationship between HMGB1 and the proinflammatory cytokine interleukin-6 (IL-6). Methods: Forty-seven subjects, American Society of Anesthesiologists physical status I and II, scheduled for major abdominal procedures, were enrolled. After intravenous medication with midazolam (0.025 mg/Kg), all patients received a standard general anesthesia protocol, by thiopentone sodium (5 mg/Kg) and fentanyl (1.4 mu g/Kg), plus injected Vecuronium (0.08 mg/Kg). Venous peripheral blood was drawn from patients at three different times, t(0): before surgery, t(1): immediately after surgical procedure; t(2): at 24 hours following intervention. Monocytes were purified by incubation with anti-CD14-coated microbeads, followed by sorting with a magnetic device. Cellular localization of HMGB1 was investigated by flow cytometry assay; HMGB1 release in the serum by Western blot. Serum samples were tested for IL-6 levels by ELISA. A one-way repeated-measures analysis ANOVA was performed to assess differences in HMGB1 concentration over time, in monocytes and serum. Results: We show that: a) cellular expression of HMGB1 in monocytes at t(1) was significantly higher as compared to t(0); b) at t(2), a significant increase of HMGB1 levels was found in the sera of patients. Such an increase was concomitant to a significant down-regulation of cellular HMGB1, suggesting that the release of HMGB1 might partially derive from mononuclear cells; c) treatment of monocytes with HMGB1 induced in vitro the release of IL-6; d) at t(2), high amounts of circulating IL-6 were detected as compared to t(0). Conclusions: This study demonstrates for the first time that surgical/anesthesia trauma is able to induce an early intracellular upregulation of HMGB1 in monocytes of surgical patients, suggesting that HMGB1 derives, at least partially, from monocytes

BRAF and NRAS mutations are heterogeneous and not mutually exclusive in nodular melanoma

Inhibitors of RAF inhibit the MAPK pathway that plays an important role in the development and progression of those melanoma carrying the V600E BRAF mutation, but there's a subset of such patients who do not respond to the therapy. Various mechanisms of drug resistance have been proposed which include the clonal heterogeneity of the tumor. We have studied a population of nodular melanoma to investigate the intratumor and intertumor heterogeneity by Laser Capture Microdissection (LCM) analysis. Our results showed that BRAF and NRAS mutations were detected in 47% and 33% of nodular melanoma, respectively, and that there is a discrepancy in mutational pattern of tumoral sample because in the 36% of patients a different mutation, in at least 1 area of the tumor, was found by LCM analysis, giving evidence of the presence of different clonal cells populations. Moreover, we found that mutations in BRAF and NRAS are not mutually exclusive because they were simultaneously present in the same tumor specimens and we observed that when the 2 different mutations were present one is a high-frequency mutation and the other is a low-frequency mutation. This was more evident in lymphonodal metastasis that resulted from wild type to mutational analysis, but showed different mutations following LCM analysis. Therefore, we believed that, when primary tumoral sample results negative to mutational analysis, if it is possible, metastases should be investigated to verify the presence of mutations. Generally, it should be searched for other mutations, in addition to BRAF V600E, so as to better understand the mechanism of drug resistance.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivitives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0

Narrative review of multiparametric ultrasound in parotid gland evaluation

Disorders affecting parotid gland represent a heterogeneous group comprising congenital, inflammatory and neoplastic diseases which show a focal or diffuse pattern of appearance. The differentiation of neoplastic from non-neoplastic conditions of parotid glands is pivotal for the diagnostic imaging. Frequently there is evidence of overlapping between the clinical and the imaging appearance of the various pathologies. The parotid gland is also often object of study with the combination of different techniques [ultrasound-computed tomography-magnetic resonance imaging (US-CT-MRI), ex.]. Compared to other dominant methods of medical imaging, US has several advantages providing images in real-time at lower cost, and without harmful use of ionizing radiation and of contrast enhancement. B-mode US, and the microvascular pattern color Doppler are usually used as first step evaluation of parotid lesions. Elastography and contrast-enhanced US (CEUS) has opened further possible perspectives to improve the differentiation between benign and malignant parotid lesions. The characterization of the parotid tumors plays a crucial role for their treatment planning and for the prediction of possible surgical complications. We present, here an updated review of the most recurrent pathologies of parotid gland focusing on the diagnostic power of multiparametric US including CEUS and ultrasound elastography (USE); limitations, advantages and the main key-points will be presented

Effect of different anaesthetic techniques on gene expression profiles in patients who underwent hip arthroplasty.

ObjectivesTo investigate the modulation of genes whose expression level is indicative of stress and toxicity following exposure to three anaesthesia techniques, general anaesthesia (GA), regional anaesthesia (RA), or integrated anaesthesia (IA).MethodsPatients scheduled for hip arthroplasty receiving GA, RA and IA were enrolled at Rizzoli Orthopaedic Institute of Bologna, Italy and the expression of genes involved in toxicology were evaluated in peripheral blood mononuclear cells (PBMCs) collected before (T0), immediately after surgery (T1), and on the third day (T2) after surgery in association with biochemical parameters.ResultsAll three anaesthesia methods proved safe and reliable in terms of pain relief and patient recovery. Gene ontology analysis revealed that GA and mainly IA were associated with deregulation of DNA repair system and stress-responsive genes, which was observed even after 3-days from anaesthesia. Conversely, RA was not associated with substantial changes in gene expression.ConclusionsBased on the gene expression analysis, RA technique showed the smallest toxicological effect in hip arthroplasty.Trial registrationClinicalTrials.gov number NCT03585647

La Padania, una regione italiana in Europa

Dettagliata analisi della area padana e delle sue caratteristiche con approfondimenti sulla struttura ed evoluzione della sua economia, delle sue risorse geo-economiche e infrastrutturali con riferimento anche alla collocazione della Padania del più ampio contesto europeo e dei mercati internazioali.- Indice #6- Introduzione, Marcello Pacini #10- Prima parte Le caratteristiche dell’area #23- Struttura ed evoluzione dell’economia padana, Alberto Bramanti e Lanfranco Senn #24- Internazionalizzazione dell’economia padana, Sergio Alessandrini #130- Il sistema dei trasporti padano: progetti e prospettive, Centro Studi sui Sistemi di Trasporto #204- Competere in prospettiva europea: la Padania nel quadro delle grandi regioni economiche d’Europa, Roberto P. Camagni #294- Pieno e vuoto. La risorsa spazio in Padania, Luigi Mazza #310- Acque e rifiuti. Da risorse a fattori limitanti lo sviluppo nel bacino del Po, Pier Francesco Ghetti #332- Seconda parte Il contesto europeo #354- Parigi-Lione dieci anni fa. Torino-Lione tra dieci anni?, Olivier Klein #356- Reti ad alta velocità e territori economici in Europa, Olivier Klein #372- Randstad Holland: sviluppo e pianificazione di una metropoli complessivamente concorrenziale, Ilaria Bramezza e Leo van den Berg #394- La regione Reno-Ruhr: la metropoli flessibile, Klaus R. Kunzmann #44

iTalian RegIstry of doUble inner branch stent graft for arch PatHology (the TRIUmPH Registry)

Objective: The objective of this study was to assess early and midterm results after endovascular aortic arch repair using a double inner branch stent graft (DIBSG) in patients with aortic arch aneurysm or dissection unfit for open surgery. Methods: Between 2012 and 2018, there were 24 patients with aortic arch disease who were treated with a single model of a DIBSG (Terumo Aortic, Glasgow, United Kingdom) in nine Italian cardiovascular centers. We investigated technical success, mortality, occurrence of major complications, and need for reintervention in a multicenter, nonrandomized, retrospective fashion. Results: The in-hospital mortality rate was 16.7%. Cerebrovascular events occurred in 25% of patients and major strokes in 12.5%. Two patients experienced a retrograde dissection (8.3%), whereas none reported any type I or type III endoleak. During a mean follow-up of 18 months (range, 1-60 months), one patient died of a nonaortic cause and one reported a nonarch-related major stroke. No late secondary intervention was needed during the follow-up. Excluding from the analysis the first six patients treated until 2014 as part of the learning curve, in-hospital mortality, major stroke, and retrograde dissection rates were 11.1%, 11.1%, and 5.6%, respectively. Conclusions: Endovascular aortic arch repair using this model of DIBSG is feasible, and results are acceptable for a new technique in a high-risk subset of patients. Operative mortality suffers the effect of a learning curve, whereas midterm aorta-related survival is promising. Endovascular repair of aortic arch disease with a DIBSG should always be considered to give high-risk patients a chance of repair. Large-scale studies are needed to assess the long-term durability of this technique