Molecular Pathology Demonstration of SARS-CoV-2 in Cytotrophoblast from Placental Tissue with Chronic Histiocytic Intervillositis, Trophoblast Necrosis and COVID-19

A subset of placentas from pregnant women having the SARS-CoV-2 infection have been found to be infected with the coronavirus using molecular pathology methods including immunohistochemistry and RNA in situ hybridization. These infected placentas can demonstrate several unusual findings which occur together—chronic histiocytic intervillositis, trophoblast necrosis and positive staining of the syncytiotrophoblast for SARS-CoV-2. They frequently also have increased fibrin deposition, which can be massive in some cases. Syncytiotrophoblast is the most frequent fetal-derived cell type to be positive for SARS-CoV-2. It has recently been shown that in a small number of infected placentas, villous stromal macrophages, termed Hofbauer cells, and villous capillary endothelial cells can also stain positive for SARS-CoV-2. This report describes a placenta from a pregnant woman with SARS-CoV-2 that had chronic histiocytic intervillositis, trophoblast necrosis, increased fibrin deposition and positive staining of the syncytiotrophoblast for SARS-CoV-2. In addition, molecular pathology testing including RNAscope and immunohistochemistry for SARS-CoV-2 and double-staining immunohistochemistry using antibodies to E-cadherin and GATA3 revealed that cytotrophoblast cells stained intensely for SARS-CoV-2. All of the cytotrophoblast cells that demonstrated positive staining for SARS-CoV-2 were in direct physical contact with overlying syncytiotrophoblast that also stained positive for the virus. The pattern of cytotrophoblast staining for SARS-CoV-2 was patchy, and there were chorionic villi having diffuse positive staining of the syncytiotrophoblast for SARS-CoV-2, but without staining of cytotrophoblast. This first detailed description of cytotrophoblast involvement by SARS-CoV-2 adds another fetal cell type from infected placentas that demonstrate viral staining

Odontoblastic Cell Quantification and Apoptosis within Pulp of Deciduous Teeth Versus Pulp of Permanent Teeth

While the odontoblast ability to respond to injury in permanent teeth (PT) is well established, there is a lack of knowledge about deciduous teeth (DT). Aim of this study was to compare the odontoblasts activity within the pulp of DT versus the pulp of PT

Decreased number of circulating endothelial progenitor cells in patients with Graves’ hyperthyroidism.

OBJECTIVE: A relevant biological role of circulating endothelial progenitor cells (EPC) was recently demonstrated. EPC are generated in the bone marrow, and interact with damaged endothelium, restoring the integrity of the monolayer. Therefore, aim of the present study was to evaluate EPC in the blood of patients with untreated Graves' hyperthyroidism (GD), in whom an increased oxidative stress was observed. DESIGN AND METHODS: Twenty-three patients with untreated active GD and 18 matched normal controls (NC) were included in the study. Circulating EPC were isolated from peripheral blood. Mononuclear cells were cultured with endothelial basal medium supplemented with EGM SingleQuots, and were identified by positive double staining after 7 days in culture. Circulating levels of C reactive protein, total antioxidant power, interleukin (IL)-6, IL- 18, monocyte chemoattractant protein-1, tumor necrosis facotr- α, soluble vascular cell adhesion molecule (VCAM) and intracellular adhesion molecule were evaluated by enzymelinked immunosorbent assay kit. EPC number was also evaluated in a subgroup of GD patients after restoration of euthyroidism. RESULTS: Systolic blood pressure resulted increased in GD patients compared with control subjects whereas diastolic blood pressure was not significantly different. Patients with GD showed an increase in circulating levels of IL-18 and VCAM-1 and a reduction of total antioxidant power (p<0.05) compared to NC. Moreover, a reduced number of EPC was observed in patients with GD compared to NC (p<0.05) which turned to NC values after restoring euthyroidism. CONCLUSION: Patients with GD showed a reduction in the physiological protective mechanisms against endothelial damage, probably induced by increased inflammation and oxidative stress

The role of chemerin in the colocalization of NK and dendritic cell subsets into inflamed tissues.

Chemerin is a chemotactic agonist recently identified as the ligand of ChemR23, a serpentine receptor expressed by mononuclear phagocytes and dendritic cells (DCs). This study shows that blood CD56(low)CD16(+) natural killer (NK) cells selectively express functional ChemR23 and that this receptor is coexpressed with CXCR1, the CXCL8 receptor, and the KIR receptors. In vitro culturing of NK cells with IL-2 or IL-15 induced a delayed and time-dependent down-regulation of ChemR23 that was associated with the inhibition of NK cell migration to chemerin. Biopsies obtained from patients with oral lichen planus presented an infiltration of CD94(+)CD3(-)CD56(+) NK cells that coexpressed ChemR23. The same biopsies were infiltrated by myeloid, DC-SIGN(+) and plasmacytoid, CD123(+)BDCA2(+), ChemR23(+) dendritic cells that were occasionally associated with NK cells. In the same histologic sections, chemerin was expressed by inflamed dermal endothelium. These findings propose a role for the ChemR23/chemerin axis in the recruitment of blood NK cells and strongly implicate chemerin as a key factor for the colocalization of NK cells and DC subsets in pathologic peripheral tissues.Clinical TrialJournal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Intracardiac Versus Transesophageal Echocardiographic Guidance for Left Atrial Appendage Occlusion: The LAAO Italian Multicenter Registry

Objectives: This study sought to evaluate the feasibility, safety, and efficacy of intracardiac echocardiography (ICE)\u2013guided versus transesophageal echocardiography (TEE)\u2013guided left atrial appendage occlusion (LAAO) by the use of Amplatzer Cardiac Plug or Amulet devices included in a large Italian registry. Background: TEE is widely used for LAAO procedure guidance. ICE may be a potential alternative imaging modality in LAAO. Methods: Data from 604 LAAO procedures performed in 16 Italian centers were reviewed. ICE-guided LAAO was performed in 187 patients, whereas TEE was used in 417 patients. Procedural success was defined as LAAO without occurrence of pericardial tamponade, stroke, systemic embolism with end organ damage, major bleeding, and device embolization. Stroke, transient ischemic attack, major bleeding, overall and cardiovascular death were analyzed. Results: CHA2DS2-VASc (congestive heart failure, hypertension, age 6575 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65 to 74 years, sex category) and HAS-BLED (hypertension, abnormal renal and liver function, stroke, bleeding, labile international normalized ratio, elderly, drugs or alcohol) scores were similar between the ICE and TEE groups. TEE implied lower procedural (delta 12 min) and fluoroscopy time (delta 5 min) when compared with ICE. Procedural success was similarly high ( 6594%) between the TEE and ICE groups with a complication rate of 6.5% for TEE versus 4.2% for ICE (odds ratio: 1.468; 95% confidence interval: 0.681 to 3.166; p = 0.327). At median follow-up of 451 days (interquartile range: 162 to 899 days), the rate of cerebral ischemic events was similar between TEE-guided and ICE-guided procedures. Conclusions: ICE-guided LAAO by means of Amplatzer devices may represent a second alternative imaging modality after an appropriate learning curve and bearing in mind that pre-procedural computed tomography imaging is mandatory. When comparing ICE with TEE, TEE remains the gold standard

Left atrial appendage closure using AMPLATZER\ue2\u84\ua2 devices: A large, multicenter, Italian registry

BACKGROUND: Left atrial appendage occlusion (LAAO) has been proven to be effective for stroke prophylaxis in patients with non-valvular atrial fibrillation (NVAF). We aim to assess the safety and efficacy of LAAO by AMPLATZER\u2122 devices in a large, multicenter, single-nation cohort of NVAF patients at high-risk of stroke and bleeding. METHODS: From December 2008 to April 2015 613 NVAF patients (75.1\ub18.0years, 62.5% male) underwent LAAO in 15 Italian centers by AMPLATZER\u2122 devices. There were no restrictions on any personal/institutional protocols with respect to indications, pre-procedural planning, device implantation, drug therapy and follow-up. All the baseline characteristics, imaging, procedural and follow-up data were collected in a single dataset. RESULTS: AMPLATZER\u2122 devices were successfully implanted in 95.4% of cases. Major complications occurred during 38 procedures (6.2%) and included more frequently major bleeding (3.3%) and pericardial tamponade (2.0%). At a mean follow-up of 20months, the overall annual rates of stroke and thromboembolic events, including those periprocedural, was 1.67% and 2.90%, respectively, consisting in a reduction in the rate of stroke and TIA of 66% compared with the risk-based expectation. Among the 218 patients undergoing transesophageal echocardiography at 6months of follow-up, device thrombosis was present in 1.8% of the patients whilst a significant or mild to moderate peri-device leak was found in 0.5% and 11.9% of cases, respectively. CONCLUSIONS: In this large, multicenter, single-nation study, LAAO with the AMPLATZER\u2122 devices showed high procedural success, early safety and mid-term efficacy for the prevention of NVAF-related thromboembolism

Defective dendritic cell migration and activation of adaptive immunity in PI3Kγ-deficient mice

Gene-targeted mice were used to evaluate the role of the gamma isoform of phosphoinositide 3-kinase (PI3Kγ) in dendritic cell (DC) migration and induction of specific T-cell-mediated immune responses. DC obtained from PI3Kγ−/− mice showed a reduced ability to respond to chemokines in vitro and ex vivo and to travel to draining lymph nodes under inflammatory conditions. PI3Kγ−/− mice had a selective defect in the number of skin Langerhans cells and in lymph node CD8α(−) DC. Furthermore, PI3Kγ−/− mice showed a defective capacity to mount contact hypersensitivity and delayed-type hypersensitivity reactions. This defect was directly related to the reduced ability of antigen-loaded DC to migrate from the periphery to draining lymph nodes. Thus, PI3Kγ plays a nonredundant role in DC trafficking and in the activation of specific immunity. Therefore, PI3Kγ may be considered a new target to control exaggerated immune reactions