A simplified genomic profiling approach predicts outcome in metastatic colorectal cancer

The response of metastatic colorectal cancer (mCRC) to the first-line conventional combination therapy is highly variable, reflecting the elevated heterogeneity of the disease. The genetic alterations underlying this heterogeneity have been thoroughly characterized through omic approaches requiring elevated efforts and costs. In order to translate the knowledge of CRC molecular heterogeneity into a practical clinical approach, we utilized a simplified Next Generation Sequencing (NGS) based platform to screen a cohort of 77 patients treated with first-line conventional therapy. Samples were sequenced using a panel of hotspots and targeted regions of 22 genes commonly involved in CRC. This revealed 51 patients carrying actionable gene mutations, 22 of which carried druggable alterations. These mutations were frequently associated with additional genetic alterations. To take into account this molecular complexity and assisted by an unbiased bioinformatic analysis, we defined three subgroups of patients carrying distinct molecular patterns. We demonstrated these three molecular subgroups are associated with a different response to first-line conventional combination therapies. The best outcome was achieved in patients exclusively carrying mutations on TP53 and/or RAS genes. By contrast, in patients carrying mutations in any of the other genes, alone or associated with mutations of TP53/RAS, the expected response is much worse compared to patients with exclusive TP53/RAS mutations. Additionally, our data indicate that the standard approach has limited efficacy in patients without any mutations in the genes included in the panel. In conclusion, we identified a reliable and easy-to-use approach for a simplified molecular-based stratification of mCRC patients that predicts the efficacy of the first-line conventional combination therapy

Clinical validation of 13-Gene DNA methylation analysis from oral brushing: a non invasive sampling procedure for early detection of oral squamous cell carcinoma. A multicentric study

1. Introduction In a recent study our research group described a non-invasive sampling procedure based on DNA methylation analysis of a set of 13 genes with a high level of accuracy (sensitivity 96.6%, specificity 100%) in the detection of squamous cell carcinoma of the oral cavity (OSCC) [1]. The purpose of the present study was to test the diagnostic performance of this non invasive sampling procedure in an italian multicentric study. 2. Materials and Methods Oral brushing specimens were collected in ten different italian units of oral medicine. Each oral medicine unit collected blindly 10 brushing specimens from patients affected by OSCC and an equal number of age and sex-matched healthy controls. 13-gene DNA methylation analysis was performed and each sample was considered positive or negative in relation to a predefined cut-off value. 3. Results 181 out of 200 planned specimens were analyzed. DNA could not be amplified in 4 cases (2.2%). 86/93 (92.5%) specimens derived from OSCC patients were detected as positive and 70/84 (83.3%) specimens derived from healthy donors showed a negative score. 4. Conclusions Data from multicentric study confirmed a high level of sensitivity of our procedure whereas level of specificity is slightly lower if compared to our previous study. These data suggest that our procedure may be proposed as a first level diagnostic test with the aim to avoid a diagnostic delay in Oral Squamous Cell Carcinoma. Conflicts of Interest: As a possible conflict of interest, L. Morandi and D.B.G. submitted a patent (the applicant is the University of Bologna) in November 2016 to the National Institute of 398 Industrial Property; however, we believe that this is a natural step of translational research (bench-to-bedside) 399 and guarantee that the scientific results are true. The remaining authors declare that they have no competing 400 interest

Anxiety and depression in keratotic oral lichen planus: a multicentric study from the SIPMO

Objectives: Oral lichen planus with exclusive keratotic reticular, papular, and/or plaque-like lesions (K-OLP) is a clinical pattern of OLP that may be associated with a complex symptomatology and psychological alteration. The aim of the study was to evaluate the prevalence of anxiety (A) and depression (D) in patients with K-OLP, analyzing the potential predictors which can affect mental health status. Methods: Three hundred K-OLP patients versus 300 healthy controls (HC) were recruited in 15 Italian universities. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), and Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A) were administered. Results: The K-OLP patients showed statistically higher scores in the NRS, T-PRI, HAM-D, and HAM-A compared with the HC (p-value < 0.001**). A and D were found in 158 (52.7%) and 148 (49.3%) K-OLP patients. Strong linear correlations were identified between HAM-A, HAM-D, NRS, T-PRI, and employment status and between HAM-D, HAM-A, NRS, T-PRI, employment status, and female gender. Multivariate logistic regression revealed that HAM-D and HAM-A showed the greatest increase in the R2 value for A and D in the K-OLP patients, respectively (DR2 = 55.5% p-value < 0.001**; DR2 = 56.5% p-value < 0.001**). Conclusions: The prevalence of A and D is higher in the K-OLP patients compared with the HC, also found in K-OLP subjects without pain, suggesting that the processing of pain may be in a certain way independent of the processing of mood. Clinical relevance: Mood disorders and pain assessment should be carefully performed in relation to K-OLP to obtain a complete analysis of the patients

Non-erythropoietic erythropoietin derivatives protect from light-induced and genetic photoreceptor degeneration

Given the high genetic heterogeneity of inherited retinal degenerations (IRDs), a wide applicable treatment would be desirable to halt/slow progressive photoreceptor (PR) cell loss in a mutation-independent manner. In addition to its erythropoietic activity, erythropoietin (EPO) presents neurotrophic characteristics. We have previously shown that adeno-associated viral (AAV) vector-mediated systemic EPO delivery protects from PR degeneration. However, this is associated with an undesired hematocrit increase that could contribute to PR protection. Non-erythropoietic EPO derivatives (EPO-D) are available which allow us to dissect erythropoiesis's role in PR preservation and may be more versatile and safe than EPO as anti-apoptotic agents. We delivered in animal models of light-induced or genetic retinal degeneration either intramuscularly or subretinally AAV vectors encoding EPO or one of the three selected EPO-D: the mutant S100E, the helix A- and B-derived EPO-mimetic peptides. We observed that (i) systemic expression of S100E induces a significantly lower hematocrit increase than EPO and provides similar protection from PR degeneration, and (ii) intraocular expression of EPO-D protects PR from degeneration in the absence of significant hematocrit increase. On the basis of this, we conclude that erythropoiesis is not required for EPO-mediated PR protection. However, the lower efficacy observed when EPO or S100E is expressed intraocularly rather than systemically suggests that hormone systemic effects contribute to PR protection. Unlike S100E, EPO-mimetic peptides preserve PR only when given locally, suggesting that different EPO-D have a different potency or mode of action. In conclusion, our data show that subretinal delivery of AAV vectors encoding EPO-D protects from light-induced and genetic PR degeneration

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

EBUS-Guided Cryobiopsy of Mediastinal Lymphonodes: The First Case Report

No abstract availabl

Surgical treatment with Ligasure® Precise of schwannoma of brachial plexus: case report

We present a case of bulky schwannoma arising from the brachial plexus treated by a new surgical device. A 38-year-old man presented with a slow-growing left-sided supraclavicular mass and complained paresthesia of the third and forth fingers of the hand and forearm weakness. Physical examination revealed Tinel’s sign. A CT-scan revealed a solid mass situated in the left profound supraclavicular fossa. The tumour was resected with the utilization of bipolar vessel sealing system (Ligasure® Precise). This device is very useful in suturless removal of masses localized in deep supraclavicular fossa. During the operation, care was taken to preserve the nerve functio

Maxillary Sinus Augmentation with Autologous and Heterologous Bone Graft: A Clinical and Radiographic Report of Immediate and Delayed Implant Placement

The aim of this study was to evaluate cumulative survival rate of implants placed on augmented maxillary sinus using a mixture of autologous bone harvested from the maxillary tuberosity and bovine-derived HA and to assess the height of the grafted material through radiographic evaluation

Efficacy of the topical 5% lidocaine medicated plaster in the treatment of chronic post-thoracotomy neuropathic pain

To assess the efficacy of the topical 5% lidocaine medicated plaster in patients with post-thoracotomy neuropathic pain