Novel heterozygous TREX1 mutation in a juvenile systemic lupus erythematosus patient with severe cutaneous involvement treated successfully with Jak-inhibitors: a case report

Juvenile systemic lupus erythematosus (jSLE) is a complex inflammatory autoimmune disorder. In the last decades, genetic factors and activation pathways have been increasingly studied to understand their potential pathogenetic role better. Genetic and transcriptional abnormalities directly involved in the type I interferon (IFN) signaling cascade have been identified through family-based and genome-wide association studies. IFNs trigger signaling pathways that initiate gene transcription of IFN-stimulated genes through the activation of JAK1, TYK2, STAT1, and STAT2. Thus, the use of therapies that target the IFN pathway would represent a formidable advance in SLE. It is well known that JAK inhibitors have real potential for the treatment of rheumatic diseases, but their efficacy in the treatment of SLE remains to be elucidated. We report the case of a 13-year-old girl affected by jSLE, carrying a novel heterozygous missense variant on Three prime Repair EXonuclease 1 (TREX1), successfully treated with baricitinib on top of mofetil mycophenolate. The TREX1 gene plays an important role in DNA damage repair, and its mutations have been associated with an overproduction of type 1 interferon. This report underlines the role of translational research in identifying potential pathogenetic pathways in rare diseases to optimize treatment

Universal testing for COVID-19 in patients undergoing cancer treatment during the second outbreak in Brescia

Background: The impact of coronavirus disease 2019 (COVID-19) has been overwhelming on patients with cancer, who may be at higher risk of developing severe disease. During the second COVID-19 outbreak in Italy, we planned universal microbiologic screening for patients scheduled for antineoplastic treatment. Methods: All patients with planned active treatment at Brescia University Radiation Oncology Department were screened for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA with repeated nasopharyngeal swabs (NPS) from October 31, 2020. Treatment continuation, suspension, or delay was modulated for patients testing positive according to clinical presentation. Results: From October 31, 2020, to February 6, 2021, 636 patients were enrolled and 1243 NPS were performed, of which 28 (2.25%) were positive. The infection rate was 2.52%; 81.3% of the patients with a positive NPS were asymptomatic, 2 had mild disease, and 1 severe disease that led to death. All patients already on treatment with mild or asymptomatic COVID-19 carried on the therapy with no or minimal delay. Median delay for patients with infection detected before treatment start was 16.5 days. Conclusions: Detected incidence of COVID-19 was lower during the second outbreak in our patients (2.52% vs 3.23%), despite the extensive testing schedule, and substantiates the high rate of asymptomatic infections and the low mortality among patients with COVID-19 (6.3% vs 38.5% during the first outbreak). Universal SARS-CoV-2 screening for all patients with planned treatment might allow early identification of patients with COVID-19, resulting in timely management that could improve clinical outcomes and prevent spread of the infection

A challenging case of pregnancy with placenta accreta and very rare irregular antibodies versus Cromer blood group system: a case report

ntroduction: This report describes the challenges of treating a pregnant woman who had a rare case of critical placenta accreta with concurrent Cromer system anti-Tc(a) and anti-Kidd A alloantibodies. No previous case of such alloimmunization in a patient with placenta accreta has been reported. Case presentation: A 28-year-old African woman with anti-Cromer Tc(a) antibodies, anti-Kidd A antibodies and placenta accreta was admitted to the obstetric emergency department at our university hospital with persistent vaginal bleeding. Her rare Cromer blood group system antibodies had been diagnosed 1 month earlier; no compatible blood had been found despite a worldwide search. We performed a cesarean section after placement of Fogarty balloons in her uterine arteries with preoperative endovascular interventional radiology. Other therapeutic interventions included preoperative iron administration to raise hemoglobin and the scheduled predeposit of autologous blood. Intraoperative therapeutic management was aimed at preventing coagulopathy and massive bleeding. With the use of alternative medical techniques determined during perioperative planning, her intraoperative blood loss was only 1000mL, despite the placenta accreta. She was discharged from the hospital 4 days after cesarean section. Conclusions: To the best of our knowledge, this is the first report of an alloimmunized patient with two different alloantibodies and concurrent high risk of bleeding because of placenta accreta. The close collaboration among obstetricians, anesthesiologists, interventional radiologists, blood bank pathologists and intensive care doctors prevented serious consequences in this patient. The exceptional feature of this case is the patient's double risk: the placenta accreta and the inability to transfuse compatible blood. These two extreme situations challenged the multidisciplinary medical team

HISTOPATHOLOGICAL FINDINGS IN SYSTEMIC SCLEROSIS-RELATED MYOPATHY: FIBROSIS AND MICROANGIOPATHY

Objectives: The objective of this study was to identify specific histopathological features of skeletal muscle involvement in systemic sclerosis (SSc) patients. Methods: A total of 35 out of 112 SSc-patients (32%, including 81% female and 68% diffuse scleroderma) presenting clinical, biological and electromyographic (EMG) features of muscle weakness, were included. Patients underwent vastus lateralis biopsy, assessed for individual pathologic features including fibrosis [type I collagen (Coll-I), transforming growth factor β (TGF-β)], microangiopathy [cluster of differentiation 31 (CD31), pro-angiogenic vascular endothelial growth factor A (VEGF-A), anti-angiogenic VEGF-A165b], immune/ inflammatory response [CD4, CD8, CD20, human leucocyte antigens ABC (HLA-ABC)], and membranolytic attack complex (MAC). SSc biopsies were compared with biopsies of (n = 35) idiopathic inflammatory myopathies (IIMs) and to (n = 35) noninflammatory myopathies (NIMs). Ultrastructural abnormalities of SSc myopathy were also analyzed by transmission electron microscopy (TEM). Results: Fibrosis in SSc myopathy (81%) is higher compared with IIM (32%, p < 0.05) and with NIM (18%, p < 0.05). Vascular involvement is dominant in SSc muscle (92%), and in IIM (78%) compared with NIM (21%, p < 0.05). In particular, CD31 shows loss of endomysial vessels in SSc myopathy compared with IIM (p < 0.05) and with NIM (p < 0.01). VEGF-A is downregulated in SSc myopathy compared with IIM (p < 0.05) and NIM (p < 0.05). Conversely, VEGF-A165b is upregulated in SSc myopathy. The SSc immune/inflammatory response suggested humoral process with majority (85%) HLA-ABC fibral neoexpression and complement deposits on endomysial capillaries MAC, compared with IIM (p < 0.05), characterized by CD4+/CD8+/B-cell infiltrate, and NIM (p < 0.05). TEM analysis showed SSc vascular alterations consisting of thickening and lamination of basement membrane and endothelial cell ‘swelling’ coupled to endomysial/perimysial fibrosis. Conclusions: Fibrosis, microangiopathy and humoral immunity are predominant in SSc myopathy, even if it is difficult to identify specific histopathological hallmarks of muscle involvement in SSc, since they could be present also in other (IIM/NIM) myopathies. © 2016, © The Author(s), 2016

Machine-Learning-Based Tool to Predict Target Prostate Biopsy Outcomes: An Internal Validation Study

Abstract: The aim of this study is to present a personalized predictive model (PPM) with a machine learning (ML) system that is able to identify and classify patients with suspected prostate cancer (PCa) following mpMRI. We extracted all the patients who underwent fusion biopsy (FB) from March 2014 to December 2019, while patients from August 2020 to April 2021 were included as a validation set. The proposed system was based on the following four ML methods: a fuzzy inference system (FIS), the support vector machine (SVM), k-nearest neighbors (KNN), and self-organizing maps (SOMs). Then, a system based on fuzzy logic (FL) + SVM was compared with logistic regression (LR) and standard diagnostic tools. A total of 1448 patients were included in the training set, while 181 patients were included in the validation set. The area under the curve (AUC) of the proposed FIS + SVM model was comparable with the LR model but outperformed the other diagnostic tools. The FIS + SVM model demonstrated the best performance, in terms of negative predictive value (NPV), on the training set (78.5%); moreover, it outperformed the LR in terms of specificity (92.1% vs. 83%). Considering the validation set, our model outperformed the other methods in terms of NPV (60.7%), sensitivity (90.8%), and accuracy (69.1%). In conclusion, we successfully developed and validated a PPM tool using the FIS + SVM model to calculate the probability of PCa prior to a prostate FB, avoiding useless ones in 15% of the cases

Responsive Nucleic Acid-Based Organosilica Nanoparticles

The development of smart nanoparticles (NPs) that encode responsive features in the structural framework promises to extend the applications of NP-based drugs, vaccines, and diagnostic tools. New nanocarriers would ideally consist of a minimal number of biocompatible components and exhibit multiresponsive behavior to specific biomolecules, but progress is limited by the difficulty of synthesizing suitable building blocks. Through a nature-inspired approach that combines the programmability of nucleic acid interactions and sol–gel chemistry, we report the incorporation of synthetic nucleic acids and analogs, as constitutive components, into organosilica NPs. We prepared different nanomaterials containing single-stranded nucleic acids that are covalently embedded in the silica network. Through the incorporation of functional nucleic acids into the organosilica framework, the particles respond to various biological, physical, and chemical inputs, resulting in detectable physicochemical changes. The one-step bottom-up approach used to prepare organosilica NPs provides multifunctional systems that combine the tunability of oligonucleotides with the stiffness, low cost, and biocompatibility of silica for different applications ranging from drug delivery to sensing

Hydrogeological effects of dredging navigable canals through lagoon shallows. A case study in Venice

For the first time a comprehensive investigation has been carried out to quantify the possible effects of dredging a navigable canal on the hydrogeological system underlying a coastal lagoon. The study is focused on the Venice Lagoon, Italy, where the port authority is planning to open a new 10m deep and 3km long canal to connect the city passenger terminal to the central lagoon inlet, thus avoiding the passage of large cruise ships through the historic center of Venice. A modeling study has been developed to evaluate the short (minutes), medium (months), and long (decades) term processes of water and pollutant exchange between the shallow aquifer system and the lagoon, possibly enhanced by the canal excavation, and ship wakes. An in-depth characterization of the lagoon subsurface along the channel has supported the numerical modeling. Piezometer and sea level records, geophysical acquisitions, laboratory analyses of groundwater and sediment samples (chemical analyses and ecotoxicity testing), and the outcome of 3-D hydrodynamic and computational fluid dynamic (CFD) models have been used to set up and calibrate the subsurface multi-model approach. The numerical outcomes allow us to quantify the groundwater volume and estimate the mass of anthropogenic contaminants (As, Cd, Cu, Cr, Hg, Pb, Se) likely leaked from the nearby industrial area over the past decades, and released into the lagoon from the canal bed by the action of depression waves generated by ships. Moreover, the model outcomes help to understand the effect of the hydrogeological layering on the propagation of the tidal fluctuation and salt concentration into the shallow brackish aquifers underlying the lagoon bottom.Facultad de Ciencias Naturales y MuseoCentro de Investigaciones Geológica