CD45-PET is a robust, non-invasive tool for imaging inflammation.

Imaging inflammation holds immense potential for advancing the diagnosis, treatment and prognosis of many conditions. The lack of a specific and sensitive positron emission tomography (PET) probe to detect inflammation is a critical challenge. To bridge this gap, we present CD45-PET imaging, which detects inflammation with exceptional sensitivity and clarity in several preclinical models.

Genomic Profiling of Cardiac Angiosarcoma Reveals Novel Targetable KDR Variants, Recurrent MED12 Mutations and a High Burden of Germline POT1Alterations.

Purpose: Cardiac angiosarcoma (CAS) is a rare, aggressive malignancy with limited treatment options. Both sporadic and familial cases occur, with recent links to germline POT1 mutations. The genomic landscape of this disease is poorly understood.

Adipocyte associated glucocorticoid signaling regulates normal fibroblast function which is lost in inflammatory arthritis.

Fibroblasts play critical roles in tissue homeostasis, but in pathologic states they can drive fibrosis, inflammation, and tissue destruction. Little is known about what regulates the homeostatic functions of fibroblasts. Here, we perform RNA sequencing and identify a gene expression program in healthy synovial fibroblasts characterized by enhanced fatty acid metabolism and lipid transport.

Reporting of Incidental Thrombotic Arteriopathy in Lung Resection Specimens: Examination of Clinical Impact.

Pulmonary thrombotic arteriopathy (PTA) can be an incidental finding in lung resections performed for various indications. Historic studies largely examined PTA in autopsies. Thus, the prevalence in surgical samples, particularly in the modern era of lung cancer screening, is poorly defined.

Leukemia inhibitory factor (LIF) receptor amplifies pathogenic activation of fibroblasts in lung fibrosis.

Unlabelled: Fibrosis drives end-organ damage in many diseases. However, clinical trials targeting individual upstream activators of fibroblasts, such as TGFβ, have largely failed. Here, we target the leukemia inhibitory factor receptor (LIFR) as a "master amplifier" of multiple upstream activators of lung fibroblasts.

A Large Postmortem Database of COVID-19 Patients Can Inform Disease Research and Public Policy Decision Making.

Context.—: Autopsies performed on COVID-19 patients have provided critical information about SARS-CoV-2's tropism, mechanisms of tissue injury, and spectrum of disease.

Objective.

Integrated Immunopeptidomic and Proteomic Analysis of COVID-19 lung biopsies.

Introduction: Severe respiratory illness is the most prominent manifestation of patients infected with SARS-CoV-2, and yet the molecular mechanisms underlying severe lung disease in COVID-19 affected patients still require elucidation. Human leukocyte antigen class I (HLA-I) expression is crucial for antigen presentation and the host's response to SARS-CoV-2.

Methods: To gain insights into the immune response and molecular pathways involved in severe lung disease, we performed immunopeptidomic and proteomic analyses of lung tissues recovered at four COVID-19 autopsy and six non-COVID-19 transplants.

SARS-CoV-2 viral liver aggregates and scarce parenchymal infection implicate systemic disease as a driver of abnormal liver function.

Background: Liver function tests (LFTs) are elevated in >50% of hospitalized individuals infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), with increased enzyme levels correlating with a more severe COVID-19 course. Despite these observations, evaluations of viral presence within liver parenchyma and viral impact on liver function remain controversial.

Methods And Results: Our work is a comprehensive immunopathological evaluation of liver tissue from 33 patients with severe, and ultimately fatal, cases of SARS-CoV-2 infection.

SARS-CoV-2 Infection Precipitating VT Storm in Patients With Cardiac Sarcoidosis.

The authors describe 3 patients presenting with cardiac sarcoidosis (CS) flare and ventricular tachycardia (VT) storm following infection with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19. COVID-19-related cardiac manifestations can vary and include arrythmias, myocarditis, and exacerbation of underlying cardiovascular disease. The exact mechanism of myocardial involvement is not clear but may include abnormal host immune response and direct myocardial injury, thereby predisposing to enhanced arrhythmic risk.

Consensus statement on the processing, interpretation and reporting of temporal artery biopsy for arteritis.

Giant cell arteritis (GCA) is the most common systemic vasculitis in adults in Europe and North America, typically involving the extra-cranial branches of the carotid arteries and the thoracic aorta. Despite advances in noninvasive imaging, temporal artery biopsy (TAB) remains the gold standard for establishing a GCA diagnosis. The processing of TAB depends largely on individual institutional protocol, and the interpretation and reporting practices vary among pathologists.

Extrafollicular IgDCD27CXCR5CD11c DN3 B cells infiltrate inflamed tissues in autoimmune fibrosis and in severe COVID-19.

Although therapeutic B cell depletion dramatically resolves inflammation in many diseases in which antibodies appear not to play a central role, distinct extrafollicular pathogenic B cell subsets that accumulate in disease lesions have hitherto not been identified. The circulating immunoglobulin D (IgD)CD27CXCR5CD11c DN2 B cell subset has been previously studied in some autoimmune diseases. A distinct IgDCD27CXCR5CD11c DN3 B cell subset accumulates in the blood both in IgG4-related disease, an autoimmune disease in which inflammation and fibrosis can be reversed by B cell depletion, and in severe COVID-19.

Recurrent Tumor Suppressor Alterations in Primary Pericardial Mesothelioma.

Primary pericardial mesotheliomas are extremely rare, accounting for <1% of all mesotheliomas, and their molecular genetic features and predisposing factors remain to be determined. Here, we report the clinicopathologic, immunohistochemical, and molecular genetic findings of 3 pericardial mesotheliomas without pleural involvement. Three cases diagnosed between 2004 and 2022 were included in the study and analyzed by immunohistochemistry and targeted next-generation sequencing (NGS); corresponding nonneoplastic tissue was sequenced in all cases.

Adipocytes regulate fibroblast function, and their loss contributes to fibroblast dysfunction in inflammatory diseases.

Fibroblasts play critical roles in tissue homeostasis, but in pathologic states can drive fibrosis, inflammation, and tissue destruction. In the joint synovium, fibroblasts provide homeostatic maintenance and lubrication. Little is known about what regulates the homeostatic functions of fibroblasts in healthy conditions.

Neuropathological features of SARS-CoV-2 delta and omicron variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continually evolving resulting in variants with increased transmissibility, more severe disease, reduced effectiveness of treatments or vaccines, or diagnostic detection failure. The SARS-CoV-2 Delta variant (B.1.

High-depth sequencing characterization of viral dynamics across tissues in fatal COVID-19 reveals compartmentalized infection.

SARS-CoV-2 distribution and circulation dynamics are not well understood due to challenges in assessing genomic data from tissue samples. We develop experimental and computational workflows for high-depth viral sequencing and high-resolution genomic analyses from formalin-fixed, paraffin-embedded tissues and apply them to 120 specimens from six subjects with fatal COVID-19. To varying degrees, viral RNA is present in extrapulmonary tissues from all subjects.

The flutemetamol analogue cyano-flutemetamol detects myocardial AL and ATTR amyloid deposits: a post-mortem histofluorescence analysis.

Background: [F]flutemetamol is a PET radioligand used to image brain amyloid, but its detection of myocardial amyloid is not well-characterized. This histological study characterized binding of fluorescently labeled flutemetamol (cyano-flutemetamol) to amyloid deposits in myocardium.

Methods: Myocardial tissue was obtained post-mortem from 29 subjects with cardiac amyloidosis including transthyretin wild-type (ATTRwt), hereditary/variant transthyretin (ATTRv) and immunoglobulin light-chain (AL) types, and from 10 cardiac amyloid-free controls.

A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients.

The molecular underpinnings of organ dysfunction in acute COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we performed single-nucleus RNA-seq and spatial transcriptomic profiling of livers from 17 COVID-19 decedents. We identified hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells.

Sustained release of BMP-2 using self-assembled layer-by-layer film-coated implants enhances bone regeneration over burst release.

Current clinical products delivering the osteogenic growth factor bone morphogenetic protein 2 (BMP-2) for bone regeneration have been plagued by safety concerns due to a high incidence of off-target effects resulting from bolus release and supraphysiological doses. Layer-by-layer (LbL) film deposition offers the opportunity to coat bone defect-relevant substrates with thin films containing proteins and other therapeutics; however, control of release kinetics is often hampered by interlayer diffusion of drugs throughout the film during assembly, which causes burst drug release. In this work, we present the design of different laponite clay diffusional barrier layer architectures in self-assembled LbL films to modulate the release kinetics of BMP-2 from the surface of a biodegradable implant.

Cardiac megakaryocytes in SARS-CoV-2-positive autopsies.

Thromboembolic phenomena are an important complication of infection by severe acute respiratory coronavirus 2 (SARS-CoV-2). Increasing focus on the management of the thrombotic complications of Coronavirus Disease 2019 (COVID-19) has led to further investigation into the role of platelets, and their precursor cell, the megakaryocyte, during the disease course. Previously published postmortem evaluations of patients who succumbed to COVID-19 have reported the presence of megakaryocytes in the cardiac microvasculature.