Establishment of a Biorepository for Down Syndrome: Experience of the Inter-Institutional Multidisciplinary BioBank - BioBIM.

BACKGROUND: Down syndrome, or Trisomy 21, is the leading genetic cause of cognitive disability in children and is associated with a high risk of several comorbidities, particularly congenital heart defects, early onset Alzheimer's disease, leukaemia, and autoimmune disorders. OBJECTIVE: This study describes the design, methods, and operational procedures employed to establish a biobank dedicated to Down syndrome that can support research projects investigating the effects of various genetic and environmental factors on this complex disease. METHODS: Blood was collected from all recruited subjects, processed, aliquoted and immediately frozen at -80 °C in the Interinstitutional Multidisciplinary BioBank (BioBIM) facilities. A small aliquot of the sample was used to perform blood tests for which analysis would not be feasible at a later date, such as blood cell counts. Each biological sample was coded, assigned a Standard PREanalytical Code, and registered in the oloBIOBANK software connected to a medical card containing all the donor's anamnestic data. All samples were stored under continuous real-time temperature recording using a freezer connected to a T-GUARD alarm system. In addition, a radiofrequency identification tracking system strictly monitored each cryopreservation operation performed throughout the sample lifecycle. RESULTS: Biological samples were collected from 454 individuals with Down syndrome from 2007 to 2023. A total of 2233 biological samples were available for research purposes, including whole blood in different anticoagulants, serum, plasma, and frozen peripheral blood mononuclear cells. The quality of the nucleic acids obtained through specific standard operating procedures demonstrated that these samples were appropriate for clinical and basic research. CONCLUSION: By establishing this biobank, we have gathered a significant number of biological samples and clinical data from individuals with Down syndrome, thereby fostering collaboration between different research groups in an open and transparent manner. Sharing expertise and resources among scientists will ultimately facilitate the transfer of knowledge to clinical practice, leading to the development of more effective therapeutic treatments to improve the outcomes and quality of life of patients with Down syndrome.

Prognostic Significance of Neutrophil-to-lymphocyte Ratio in the Framework of the 8th TNM Edition for Breast Cancer.

BACKGROUND/AIM: To investigate whether neutrophil-to-lymphocyte ratio (NLR) might represent an additional biological criterion able to identify patients with worse prognosis within the 8th edition TNM prognostic staging system for breast cancer (BC). PATIENTS AND METHODS: Pre-treatment NLR was retrospectively analyzed in 475 BC women prospectively followed for a mean time of 3.8 years. The optimal NLR cutoff, identified by ROC analysis, was set at 2. RESULTS: Elevated pre-treatment NLR was associated with worse disease-free survival (DFS) (HR=2.28) and overall survival (OS) (HR=3.39). The prognostic value of NLR was mostly evident in stage I BC (HR for DFS=2.89; HR for OS=1.30), in whom NLR significantly stratified patients who developed distant metastasis (HR= 4.62), but not local recurrence. CONCLUSION: NLR might provide important information in risk stratification, especially in stage I BC patients in whom the presence of a high NLR might raise the question as to whether they should be more aggressively managed.

C-arm cone-beam CT-guided transthoracic lung core needle biopsy as a standard diagnostic tool: an observational study.

C-arm cone-beam computed tomography (CT)-guided transthoracic lung core needle biopsy (CNB) is a safe and accurate procedure for the evaluation of patients with pulmonary nodules. This article will focus on the clinical features related to CNB in terms of diagnostic performance and complication rate. Moreover, the concept of categorizing pathological diagnosis into 4 categories, which could be used for clinical management, follow-up, and quality assurance is also introduced. We retrospectively collected data regarding 375 C-arm cone-beam CT-guided CNBs from January 2010 and June 2014. Clinical and radiological variables were evaluated in terms of success or failure rate. Pathological reports were inserted in 4 homogenous groups (nondiagnostic--L1, benign--L2, malignant not otherwise specified--L3, and malignant with specific histotype--L4), defining for each category a hierarchy of suggested actions. The sensitivity, specificity, and positive and negative predictive value and accuracy for patients subjected to CNBs were of 96.8%, 100%, 100%, 100%, and 97.2%, respectively. Roughly 75% of our samples were diagnosed as malignant, with 60% lung adenocarcinoma diagnoses. Molecular analyses were performed on 85 malignant samples to verify applicability of targeted therapy. The rate of "nondiagnostic" samples was 12%. C-arm cone-beam CT-guided transthoracic lung CNB can represent the gold standard for the diagnostic evaluation of pulmonary nodules. A clinical and pathological multidisciplinary evaluation of CNBs was needed in terms of integration of radiological, histological, and oncological data. This approach provided exceptional performances in terms of specificity, positive and negative predictive values; sensitivity in our series was lower compared with other large studies, probably due to the application of strong criteria of adequacy for CNBs (L1 class rate). The satisfactory rate of collected material was evaluated not only in terms of merely diagnostic performances but also for predictive results by molecular analysis.

A donor cornea with metastatic cells from a cutaneous malignant melanoma.

PURPOSE: To describe the case of a donor cornea that showed hematogenous metastatic spread of cutaneous melanoma to the sclerocorneal limbus. METHODS: Corneal tissue obtained from a donor with cutaneous malignant melanoma was evaluated for endothelial cell density, corneal transparency, and epithelial morphology. Subsequently, hematoxylin and eosin staining and immunohistochemical characterization using S100, HMB45, Melan-A, and CD34 antibodies were performed on the corneal sections. RESULTS: The corneal tissue was transparent with high endothelial cell density; it was graded as being suitable for transplantation according to the current eye bank criteria. However, the aggressiveness of the donor's cancer and the diffuse melanosis of the sclera led to the suspicion of malignant melanoma metastasis to the cornea. Histochemical analysis of the corneoscleral rim showed small aggregates rich in pigmented cells that were localized in cleft-like structures in the sclera, at the sclerocorneal interface and in the peripheral avascular portion of the cornea. The aggregates were positive for the melanocytic tumor markers S100, HMB45, and Melan-A; the rims of the clefts expressed the panvascular CD34 antigen, which was suggestive of neovascularization. CONCLUSIONS: Corneal tissue from a donor with malignant cutaneous melanoma displayed neoplastic lesions of melanocytic origin that had spread from a primitive melanoma through hematogenous routes to the sclerocorneal limbus. On the basis of this finding, we believe that having a metastatic cutaneous malignant melanoma could in some cases be reviewed as an exclusionary criterion for undergoing cornea transplantation.