Development of a Nomogram Predicting the Risk of Persistence/Recurrence of Cervical Dysplasia

Background: Cervical dysplasia persistence/recurrence has a great impact on women's health and quality of life. In this study, we investigated whether a prognostic nomogram may improve risk assessment after primary conization. Methods: This is a retrospective multi-institutional study based on charts of consecutive patients undergoing conization between 1 January 2010 and 31 December 2014. A nomogram assessing the importance of different variables was built. A cohort of patients treated between 1 January 2015 and 30 June 2016 was used to validate the nomogram. Results: A total of 2966 patients undergoing primary conization were analyzed. The median (range) patient age was 40 (18-89) years. At 5-year of follow-up, 6% of patients (175/2966) had developed a persistent/recurrent cervical dysplasia. Median (range) recurrence-free survival was 18 (5-52) months. Diagnosis of CIN3, presence of HR-HPV types, positive endocervical margins, HPV persistence, and the omission of HPV vaccination after conization increased significantly and independently of the risk of developing cervical dysplasia persistence/recurrence. A nomogram weighting the impact of all variables was built with a C-Index of 0.809. A dataset of 549 patients was used to validate the nomogram, with a C-index of 0.809. Conclusions: The present nomogram represents a useful tool for counseling women about their risk of persistence/recurrence after primary conization. HPV vaccination after conization is associated with a reduced risk of CIN2+

Genetic Variability and Family Relationships in a Reintroduced Osprey (<i>Pandion haliaetus</i>) Population: A Field-Lab Integrated Approach

Reintroductions represent an opportunity to restore local biodiversity and reverse the effect of taxa extinction. However, they need feasibility and monitoring plans before and during their implementation to ensure concrete and lasting results. During the 20th century, the osprey (Pandion haliaetus) underwent a severe population decline in many European countries due to direct persecution and coast exploitation. In the 1960s–1970s, it was declared extinct as a breeder in Italy. In 2004, the Maremma Regional Park (Tuscany, central Italy) started a reintroduction project by capturing and releasing, from 2006 to 2010, 33 juvenile Corsican ospreys on the southern coast of Tuscany. The settlement of the first breeding pair in 2011 was the initial sign of the success of the reintroduction project, then further pairs settled from 2011 onward. A total of 81 feather or blood samples were collected for DNA extraction from both translocated (2006–2010) and newborn individuals (2011–2021). Individuals were analyzed at 16 microsatellite loci to verify any changes in genetic variability over time and to set out a protocol for the reconstruction of kinship for conservation and management purposes. We did not observe a reduction in genetic variability between the two sampling periods, although we found a slight sign of the founder effect in the reestablished population. A strong genetic differentiation was observed between this Mediterranean population and an injured osprey from a Northern European population, thus confirming the importance of considering the local genetic pool in any reintroduction project. Monogamous behavior was confirmed by family reconstruction, which allowed the identification of clear kinship relationships. Our findings indirectly inform on the genetic variability of the population during the 16-year period from the start of the project and provide useful insights for its long-term conservation

Complex expression of BDNF and reelin in the developing and adult brain of TgCRND8 mice

This study is aimed at characterizing molecular pathways common to neurodevelopment and neurodegeneration. Indeed, it is now evident that neurodegenerative processes can be rooted in aberrant expression of neurodevelopment-related genes. Among various genes, BDNF and reelin are good candidates as they play fundamental roles during brain development/maturation and adult functions and their expression is often altered in neurodegeneration. On the other hand, PSEN1, which is involved in A β processing, also plays crucial roles in the developing brain

Epidemiology, management and outcome of status epilepticus in adults: single-center Italian survey

: The official variations of status epilepticus (SE) International League Against Epilepsy (ILAE, 2015) diagnostic criteria and the non-convulsive SE (NCSE) Salzburg Consensus Criteria (2013), impose the collection of updated population-based epidemiological Italian data. In this study, we aimed at evaluating (a) the frequency of SE in our hospital adopting the new ILAE 2015 SE diagnostic criteria and NCSE Salzburg Consensus Criteria, (b) the frequency of adherence to current treatment guidelines for SE and their relationship with patients' outcome, and (c) reliability of standardized prognostic scales (Status Epilepticus Severity Score-STESS-and modified STESS) for short-term outcome prediction in the setting of the newest diagnostic criteria for SE and NCSE. Detailed clinical and electrophysiological data collected in a 1-year retrospective hospital-based single-center survey on SE at Parma Hospital, Northern Italy are provided. Non-adherence to current treatment guidelines was recorded in around 50% cases, but no relation to outcome was appreciated. Mortality in our cohort increased from 30 to 50% when follow-up was extended to 30&nbsp;days. STESS score was strongly correlated with short-term mortality risk (OR 18.9, 2.2-163.5, CI), and we confirm its role as easy-to-use tool for outcome evaluation also when the new ILAE diagnostic SE criteria are applied

Migration and wintering strategies in vulnerable Mediterranean Osprey populations

International audienc

The prometastatic relevance of tumor‐infiltrating B lymphocytes in laryngeal squamous cell carcinoma

Abstract Objectives Laryngeal squamous cell carcinomas (LSCCs) typically have an excellent prognosis for stage I tumors but a significant risk of locoregional and distant recurrence for intermediate to advanced disease. This study will investigate the clinical relevance of the tumor microenvironment in a large cohort of treatment‐naïve patients affected by stage II–IV LSCC. Methods Whole slide‐based digital pathology analysis was applied to measure six immune cell populations identified by immunohistochemistry (IHC) staining for CD3, CD8, CD20, CD66b, CD163 and CD38. Survival analysis was performed by Cox proportional hazards models and unsupervised hierarchical clustering using the k‐means method. Double IHC staining and in‐situ hybridisation by RNAscope allowed further analysis of a protumoral B cell population. Results A cohort of 98 patients was enrolled and analysed. The cluster of immune‐infiltrated LSCCs demonstrated a significantly worse disease‐specific survival rate. We also discovered a new association between high CD20+ B cells and a greater risk of distant recurrence. The phenotypic analysis of infiltrating CD20+ B cells showed a naïve (BCL6−CD27−Mum1−) regulatory phenotype, producing TGFβ but not IL10, according to an active TGFβ pathway, as proved by positive pSMAD2 staining. Conclusion The identification of regulatory B cells in the context of LSCC, along with the activation of the TGFβ pathway, could provide the basis for new trials investigating the efficacy of already available molecules targeting the TGFβ pathway in the treatment of LSCC

Outcomes of High-Grade Cervical Dysplasia with Positive Margins and HPV Persistence after Cervical Conization

The objective of this work is to assess the 5-year outcomes of patients undergoing conization for high-grade cervical lesions that simultaneously present as risk factors in the persistence of HPV infection and the positivity of surgical resection margins. This is a retrospective study evaluating patients undergoing conization for high-grade cervical lesions. All patients included had both positive surgical margins and experienced HPV persistence at 6 months. Associations were evaluated with Cox proportional hazard regression and summarized using hazard ratio (HR). The charts of 2966 patients undergoing conization were reviewed. Among the whole population, 163 (5.5%) patients met the inclusion criteria, being at high risk due to the presence of positive surgical margins and experiencing HPV persistence. Of 163 patients included, 17 (10.4%) patients developed a CIN2+ recurrence during the 5-year follow-up. Via univariate analyses, diagnosis of CIN3 instead of CIN2 (HR: 4.88 (95%CI: 1.10, 12.41); p = 0.035) and positive endocervical instead of ectocervical margins (HR: 6.44 (95%CI: 2.80, 9.65); p &lt; 0.001) were associated with increased risk of persistence/recurrence. Via multivariate analyses, only positive endocervical instead of ectocervical margins (HR: 4.56 (95%CI: 1.23, 7.95); p = 0.021) were associated with worse outcomes. In this high-risk group, positive endocervical margins is the main risk factor predicting 5-year recurrence