Breast cancer and communication: Monocentric experience of a self-assessment questionnaire

Background: The communication of the diagnosis of breast cancer induces to the patient a strong psychological trauma. Radiologists are at the forefront of communicating, either for a biopsy or the probable diagnosis of malignancy. This is a complex task, which requires the knowledge and application of correct “communicative models”, among which the SPIKES protocol rep-resents a fundamental reference. Design and methods: 110 patients, with a history of breast cancer, filled out a questionnaire consisting of six questions: five aimed at defining communication compliance with the SPIKES protocol, the sixth, consisting of six feelings, aimed at the knowledge of the next emotional state. Results: Regarding compliance with various “strategic points” of the SPIKES protocol, questionnaires show that 70% of patients reported no omissions, while the remaining 30% reported omissions relatively to perception (56%), emotions (23%), setting (13%), knowledge (6%) and invitation (2%). The results showed the existence of a correlation between the final emotional state and the correct application of the SPIKES protocol; in fact, patients who reacted with a positive final emotional state-reported greater adherence to the strategic points of the SPIKES protocol. Conclusions: In healthcare, knowing the communicative compliance of a team in giving “bad news” is fundamental, especially in breast cancer. The SPIKES protocol is recognized by the Literature as a fundamental reference able to affect “positively” the emotional state of patients. The proposed questionnaire is a valid tool to identify the weak points of communication and related criticalities, to improve clinical practice

Dysregulation of NF–Y splicing drives metabolic rewiring and aggressiveness in colon cancer

NF-Y is an evolutionarily conserved transcription factor that binds specifically to the CCAAT elements of eukaryotic genes, most of which frequently deregulated in cancer. NF-YA, the regulatory subunit of the NF-Y complex, has two isoforms generated by alternative splicing, NF-YAl and NF-YAs, which differ in the transactivation domain. Transcriptomic data from The Cancer Genome Atlas (TCGA) database highlighted a significant increase in the expression of NF-YAs at the expense of NF-YAl in colorectal cancer (CRC), compared to healthy tissues. Despite this, high NF-YAl levels predict lower patients’ survival and distinguish the mesenchymal molecular subtype CMS4, which is characterized by the worst prognosis. Through the analysis of 3D cellular models, we demonstrated that altered expression of genes related to extracellular matrix and epithelial-mesenchymal transition sustains enhanced migratory and invasive behavior of NF-YAl-transduced cells. Moreover, the integration of metabolomics, bioenergetics and transcriptional analyses demonstrated a direct role for NFYAl in metabolic flexibility of cancer cells that adjust their metabolism in response to environmental changes to potentiate migration. The zebrafish xenograft model confirmed the metastatic potential triggered by NF-YAl in CRC cells. Altogether, our data highlight the transcriptional role of NF-YAl in CRC aggressiveness and suggest splice-switching strategies to hinder NF-YAl-induced metastatic dissemination

Automated computation and analysis of accuracy metrics in stereoencephalography

Background: Implantation accuracy of electrodes during neurosurgical interventions is necessary to ensure safety and efficacy. Typically, metrics are computed by visual inspection which is tedious, prone to inter-/intra-observer variation, and difficult to replicate across sites. New Method: We propose an automated approach for computing implantation metrics and investigate potential sources of error. We focus on accuracy metrics commonly reported in the literature to validate our approach against metrics computed manually including entry point (EP) and target point (TP) localisation errors and angle differences between planned and implanted trajectories in 15 patients with a total of 158 stereoelectroencephalography (SEEG) electrodes. We evaluate the effect of line-of-best-fit approaches, EP definition and lateral versus Euclidean distance on metrics to provide recommendations for reporting implantation accuracy metrics. Results: We found no bias between manual and automated approaches for calculating accuracy metrics with limits of agreement of ±1 mm and ±1°. Automated metrics are robust to sources of errors including registration and electrode bending. We observe the highest error in EP deviations of μ = 0.25 mm when the post-implantation CT is used to define the point of entry. Comparison with Existing Method(s): We found no reports of automated approaches for quality assessment of SEEG electrode implantation. Neither the choice of metrics nor the possible errors that could occur have been investigated previously. Conclusions: Our automated approach is useful to avoid human errors, unintentional bias and variation that may be introduced when manually computing metrics. Our work is relevant and timely to facilitate comparisons of studies reporting implantation accuracy

A generative model of hyperelastic strain energy density functions for multiple tissue brain deformation

PURPOSE: Estimation of brain deformation is crucial during neurosurgery. Whilst mechanical characterisation captures stress-strain relationships of tissue, biomechanical models are limited by experimental conditions. This results in variability reported in the literature. The aim of this work was to demonstrate a generative model of strain energy density functions can estimate the elastic properties of tissue using observed brain deformation. METHODS: For the generative model a Gaussian Process regression learns elastic potentials from 73 manuscripts. We evaluate the use of neo-Hookean, Mooney-Rivlin and 1-term Ogden meta-models to guarantee stability. Single and multiple tissue experiments validate the ability of our generative model to estimate tissue properties on a synthetic brain model and in eight temporal lobe resection cases where deformation is observed between pre- and post-operative images. RESULTS: Estimated parameters on a synthetic model are close to the known reference with a root-mean-square error (RMSE) of 0.1 mm and 0.2 mm between surface nodes for single and multiple tissue experiments. In clinical cases, we were able to recover brain deformation from pre- to post-operative images reducing RMSE of differences from 1.37 to 1.08 mm on the ventricle surface and from 5.89 to 4.84 mm on the resection cavity surface. CONCLUSION: Our generative model can capture uncertainties related to mechanical characterisation of tissue. When fitting samples from elastography and linear studies, all meta-models performed similarly. The Ogden meta-model performed the best on hyperelastic studies. We were able to predict elastic parameters in a reference model on a synthetic phantom. However, deformation observed in clinical cases is only partly explained using our generative model

Anti-CD 20 monoclonal antibody (rituximab) treatment for inflammatory ocular diseases

Rituximab is a monoclonal antibody directed against the CD20 antigen expressed on B cells and widely used in the treatment of non-Hodgkin's lymphoma and rheumatoid arthritis. There is a growing amount of literature which suggests that rituximab may be useful for inflammatory ocular diseases and intraocular lymphoma. Few cases have been reported on treatment of refractory scleritis, peripherative ulcerative keratitis, uveitis and ocular surface inflammatory disorders. Rituximab may be effective in the treatment of ocular inflammatory diseases in particular the most aggressive, recalcitrant and sight-threatening forms of inflammation such as uveitis associated to juvenile idiopathic arthritis. We review the literature covering the use of Rituximab in these conditions and report our results on the efficacy of Rituximab in the treatment of 8 children with very severe and long-standing uveitis who failed to respond to one or more TNF blockers. Our patients showed improvement in activity of uveitis, reduction of concomitant corticosteroids and immunosuppressants after a mean follow-up time of 14.87 months on rituximab. No serious adverse events were encountered in our treated patients. Although further studies are needed for assessing the efficacy of rituximab and the exact dosing regimen, rituximab may be considered as a treatment alternative in patients with the most aggressive forms of inflammatory ocular diseases who fail to respond to conventional and anti-TNF immunosuppressive agent

First experimental results of the spatial resolution of RSD pad arrays read out with a 16-ch board

Resistive Silicon Detectors (RSD, also known as AC-LGAD) are innovative silicon sensors, based on the LGAD technology, characterized by a continuous gain layer that spreads across the whole sensor active area. RSDs are very promising tracking detectors, thanks to the combination of the built-in signal sharing with the internal charge multiplication, which allows large signals to be seen over multiple read-out channels. This work presents the first experimental results obtained from a 3$\times$4 array with 200~\mum~pitch, coming from the RSD2 production manufactured by FBK, read out with a 16-ch digitizer. A machine learning model has been trained, with experimental data taken with a precise TCT laser setup, and then used to predict the laser shot positions, finding a spatial resolution of ~ 5.5 um

Wide-field spectrally resolved quantitative fluorescence imaging system: toward neurosurgical guidance in glioma resection

In high-grade glioma surgery, tumor resection is often guided by intraoperative fluorescence imaging. 5-aminolevulinic acid-induced protoporphyrin IX (PpIX) provides fluorescent contrast between normal brain tissue and glioma tissue, thus achieving improved tumor delineation and prolonged patient survival compared with conventional white-light-guided resection. However, commercially available fluorescence imaging systems rely solely on visual assessment of fluorescence patterns by the surgeon, which makes the resection more subjective than necessary. We developed a wide-field spectrally resolved fluorescence imaging system utilizing a Generation II scientific CMOS camera and an improved computational model for the precise reconstruction of the PpIX concentration map. In our model, the tissue’s optical properties and illumination geometry, which distort the fluorescent emission spectra, are considered. We demonstrate that the CMOS-based system can detect low PpIX concentration at short camera exposure times, while providing high-pixel resolution wide-field images. We show that total variation regularization improves the contrast-to-noise ratio of the reconstructed quantitative concentration map by approximately twofold. Quantitative comparison between the estimated PpIX concentration and tumor histopathology was also investigated to further evaluate the system

The potential role of the extracellular matrix in the activity of trabectedin in UPS and L-sarcoma: evidences from a patient‐derived primary culture case series in tridimensional and zebrafish models

Background: Soft tissue sarcomas (STS) are a rare group of solid neoplasm including among others liposarcoma, leiomyosarcoma (L-sarcoma) and undifferentiated pleomorphic sarcoma (UPS) entities. The current first-line treatment is represented by anthracycline based- regimens, second-line may include trabectedin. Currently the activity of trabectedin and its mechanism of action is not completely elucidated. Methods: Taking the advantages of our 3D patient-derived primary culture translational model we performed genomic-, chemobiogram, proteomic- and in vivo analysis in a UPS culture (S1). Furthermore pharmacological profiling of a UPS and L-sarcoma patient-derived case series and in silico analysis were carried out. Results: Trabectedin exhibited an increased activity in 3D respect to 2D cultures suggesting an extracellular matrix (ECM) and timp1 involvement in its mechanism of action. Moreover 3D S1 xenotranspanted zebrafish model showed an increased sensitivity to trabectedin. Finally the results were further validated in a UPS and L-sarcoma case series. Conclusions: Taken together these results confirmed the activity of trabectedin in these STS histotypes. Moreover the data underline the ECM involvement in the cytotoxic effect mediated by trabectedin and could open the door for researches aimed to focus on the patient setting that could benefit from this agent

Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: fundamentals of care for uveitis (focus) initiative

Topic: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. Clinical Relevance: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. Methods: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic reviewof the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE,CINAHL,SCOPUS,BIOSIS, andWeb of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review.Atotal of 44 globally representativegroupmembersmet in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. Results: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Conclusions: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents

Asbestos: a hidden player behind the cholangiocarcinoma increase? Findings from a case–control analysis

PURPOSES: We conducted a case–control analysis to explore the association between occupational exposure to asbestos and cholangiocarcinoma (CC). METHODS: The study was based on historical data from 155 consecutive patients with CC [69 intrahepatic CC (ICC) and 86 extrahepatic CC (ECC)] referred to Sant’Orsola-Malpighi University Hospital between 2006 and 2010. The cases were individually matched by calendar period of birth, sex, and region of residence to historical hospital and population controls. Occupational exposure to asbestos was retrospectively assessed considering job titles obtained from work histories. Separate conditional logistic regression models were applied for ECC and ICC. Estimates were adjusted for smoking status and socioeconomic class. RESULTS: We matched 149 controls (median birth year: 1947; males: 56 %) to 41 cases of ICC (median birth year: 1946; males: 56 %) and 212 controls (median birth year: 1945; males: 48 %) to 59 cases of ECC (median birth year: 1945; males 51 %); 53 cases were not matched due to residence or birth year. We found an increased risk of ICC in workers exposed to asbestos (adjusted OR 4.81, 95 % CI 1.73–13.33); we also observed suggestive evidence that asbestos exposure might be associated with ECC (adjusted OR 2.09, 95 % CI 0.83–5.27). Sensitivity analysis restricted to patients from the Province of Bologna produced confirmatory figures. CONCLUSIONS: Our findings suggest that ICC could be associated with asbestos exposure; a chronic inflammatory pathway is hypothesized. Exposure to asbestos could be one of the determinants of the progressive rise in the incidence of ICC during the last 30 years