A Targeted Proteomics Approach for Screening Serum Biomarkers Observed in the Early Stage of Type I Endometrial Cancer

Endometrial cancer (EC) is the most common gynecologic malignancy, and it arises in the inner part of the uterus. Identification of serum biomarkers is essential for diagnosing the disease at an early stage. In this study, we selected 44 healthy controls and 44 type I EC at tumor stage 1, and we used the Immuno-oncology panel and the Target 96 Oncology III panel to simultaneously detect the levels of 92 cancer-related proteins in serum, using a proximity extension assay. By applying this methodology, we identified 20 proteins, associated with the outcome at binary logistic regression, with a p-value below 0.01 for the first panel and 24 proteins with a p-value below 0.02 for the second one. The final multivariate logistic regression model, combining proteins from the two panels, generated a model with a sensitivity of 97.67% and a specificity of 83.72%. These results support the use of the proposed algorithm after a validation phase

Trabecular bone score (TBS) in the assessment of bone microarchitecture in acromegaly

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The accuracy of burn depth diagnosis: Clinical assessment before and after enzymatic debridement

Abstract Introduction The most common technique used to determine burn depth is clinical assessment by experienced burn surgeons, although this has been shown to be reliable in only 60–75% of the cases. Overestimation of burn depth may result in needles surgery, while burn depth underestimation can led to an increased length of stay in the hospital, risk of contracture and hypertrophic scar formation. The aim of this study was to assess the clinical evaluation of burn depth before and after enzymatic debridement with Nexobrid®. Methods The study model was retrospective. 69 patient records were collected at our burn units, from Jan 2018 to Jan 2019. Each target wound was directly assessed by a single expert physician before and after enzymatic debridement. It was investigated whether the expert, by single wound, would have indicated the need for skin grafts before treatment with Nexobrid® and after treatment. Results Prior to treatment with Nexobrid®, the expert physician assessed that a graft was necessary for 47/69 patients (68.1%). Following debridement, the same expert deemed that the patients needing a graft were 19/69 (27.5%); analysing K-agreement, a 40.6% discrepancy between the pre and post-treatment opinion with Nexobrid® was observed. Discussion The use of Nexobrid® enzymatic debridement can positively affect burn depth clinical assessment, increasing its specificity and sensitivity, without any need for delay. This can lead to a significant change in clinical practice, minimizing the use of surgery, therefore increasing quality and precision of the reconstructive phase

Induction of Expandable Tissue-Specific Stem/Progenitor Cells through Transient Expression of YAP/TAZ

The ability to induce autologous tissue-specific stem cells in culture could have a variety of applications in regenerative medicine and disease modeling. Here we show that transient expression of exogenous YAP or its closely related paralogue TAZ in primary differentiated mouse cells can induce conversion to a tissue-specific stem/progenitor cell state. Differentiated mammary gland, neuronal, and pancreatic exocrine cells, identified using a combination of cell sorting and lineage tracing approaches, efficiently convert to proliferating cells with properties of stem/progenitor cells of their respective tissues after YAP induction. YAP-induced mammary stem/progenitor cells show molecular and functional properties similar to endogenous MaSCs, including organoid formation and mammary gland reconstitution after transplantation. Because YAP/TAZ function is also important for self-renewal of endogenous stem cells in culture, our findings have implications for understanding the molecular determinants of the somatic stem cell state

The "Brunella" project: preparation and study of a mysticete from the Early Pliocene of Tuscany

• A project is being carried out at Poggio alle Mura that will allow the preparation and study of a balaenopterid whale from the early Pliocene of Tuscany together with its associated biota. • Up to now, the project resulted in the preparation of 18 vertebrae, the skull and an ulna of the whale. • The associated biota includes 18 mollusk species, 2 sea urchin species, 10 shark teeth and thousands of fish remains from the sediment surrounding the skull. • A wealth of educational activities is being carried out at the laboratory of Poggio alle Mura that are directed to schools and citizens

Italian recommendations on enzymatic debridement in burn surgery.

Abstract Introduction Nexobrid®, a bromelain-based type of enzymatic debridement, has become more prevalent in recent years. We present the recommendations on enzymatic debridement (Nexobrid®)'s role based on the practice knowledge of expert Italian users. Methods The Italian recommendations, endorsed by SIUST (Italian Society of Burn Surgery), on using enzymatic debridement to remove eschars for burn treatment were defined. The definition followed a process to evaluate the level of agreement (a measure of consensus) among selected experts, representing Italian burn centers, concerning defined clinical aspects of enzymatic debridement. The consensus involved a multi-phase process based on the Delphi method. Results The consensus panel included experts from Italy with a combined experience of 1068 burn patients treated with enzymatic debridement. At the end of round 3 of the Delphi method, the panel reached 100% consensus on 26 out of 27 statements. The panel achieved full, strong consensus (all respondents strongly agreed on the statement) on 24 out of 27 statements. Discussion The statements provided by the Italian consensus panel represent a "ready to use" set of recommendations for enzymatic debridement in burn surgery that both draw from and complete the existing scientific literature on the topic. These recommendations are specific to the Italian experience and are neither static nor definitive. As such, they will be updated periodically as further quality evidence becomes available

How the First Year of the COVID-19 Pandemic Impacted Patients’ Hospital Admission and Care in the Vascular Surgery Divisions of the Southern Regions of the Italian Peninsula

Background: To investigate the effects of the COVID-19 lockdowns on the vasculopathic population. Methods: The Divisions of Vascular Surgery of the southern Italian peninsula joined this multicenter retrospective study. Each received a 13-point questionnaire investigating the hospitalization rate of vascular patients in the first 11 months of the COVID-19 pandemic and in the preceding 11 months. Results: 27 out of 29 Centers were enrolled. April-December 2020 (7092 patients) vs. 2019 (9161 patients): post-EVAR surveillance, hospitalization for Rutherford category 3 peripheral arterial disease, and asymptomatic carotid stenosis revascularization significantly decreased (1484 (16.2%) vs. 1014 (14.3%), p = 0.0009; 1401 (15.29%) vs. 959 (13.52%), p = 0.0006; and 1558 (17.01%) vs. 934 (13.17%), p < 0.0001, respectively), while admissions for revascularization or major amputations for chronic limb-threatening ischemia and urgent revascularization for symptomatic carotid stenosis significantly increased (1204 (16.98%) vs. 1245 (13.59%), p < 0.0001; 355 (5.01%) vs. 358 (3.91%), p = 0.0007; and 153 (2.16%) vs. 140 (1.53%), p = 0.0009, respectively). Conclusions: The suspension of elective procedures during the COVID-19 pandemic caused a significant reduction in post-EVAR surveillance, and in the hospitalization of asymptomatic carotid stenosis revascularization and Rutherford 3 peripheral arterial disease. Consequentially, we observed a significant increase in admissions for urgent revascularization for symptomatic carotid stenosis, as well as for revascularization or major amputations for chronic limb-threatening ischemia

Systemic Inhibition of NF-κB Activation Protects from Silicosis

Background: Silicosis is a complex lung disease for which no successful treatment is available and therefore lung transplantation is a potential alternative. Tumor necrosis factor alpha (TNFα) plays a central role in the pathogenesis of silicosis. TNFα signaling is mediated by the transcription factor, Nuclear Factor (NF)-κB, which regulates genes controlling several physiological processes including the innate immune responses, cell death, and inflammation. Therefore, inhibition of NF-κB activation represents a potential therapeutic strategy for silicosis. Methods/Findings: In the present work we evaluated the lung transplant database (May 1986-July 2007) at the University of Pittsburgh to study the efficacy of lung transplantation in patients with silicosis (n = 11). We contrasted the overall survival and rate of graft rejection in these patients to that of patients with idiopathic pulmonary fibrosis (IPF, n = 79) that was selected as a control group because survival benefit of lung transplantation has been identified for these patients. At the time of lung transplantation, we found the lungs of silica-exposed subjects to contain multiple foci of inflammatory cells and silicotic nodules with proximal TNFα expressing macrophage and NF-κB activation in epithelial cells. Patients with silicosis had poor survival (median survival 2.4 yr; confidence interval (CI): 0.16-7.88 yr) compared to IPF patients (5.3 yr; CI: 2.8-15 yr; p = 0.07), and experienced early rejection of their lung grafts (0.9 yr; CI: 0.22-0.9 yr) following lung transplantation (2.4 yr; CI:1.5-3.6 yr; p<0.05). Using a mouse experimental model in which the endotracheal instillation of silica reproduces the silica-induced lung injury observed in humans we found that systemic inhibition of NF-κB activation with a pharmacologic inhibitor (BAY 11-7085) of IκBα phosphorylation decreased silica-induced inflammation and collagen deposition. In contrast, transgenic mice expressing a dominant negative IκBα mutant protein under the control of epithelial cell specific promoters demonstrate enhanced apoptosis and collagen deposition in their lungs in response to silica. Conclusions: Although limited by its size, our data support that patients with silicosis appear to have poor outcome following lung transplantation. Experimental data indicate that while the systemic inhibition of NF-κB protects from silica-induced lung injury, epithelial cell specific NF-κB inhibition appears to aggravate the outcome of experimental silicosis. © 2009 Di Giuseppe et al