<Superscript>18</Superscript>F-FDG-PET/CT Imaging to Diagnose Septic Emboli and Mycotic Aneurysms in Patients with Endocarditis and Cardiac Device Infections

Purpose of review

This review analyzes recent studies evaluating the diagnostic value of ¹⁸F-FDG-PET/CT for the detection of peripheral emboli and secondary infectious foci in patients with infective endocarditis and cardiac device infections.

Recent findings

Detection of extracardiac septic localizations in patients with infective endocarditis and cardiac device infections is crucial, as it may impact the diagnosis, prognosis, and therapeutic management. Recent literature substantiated the clinical usefulness of ¹⁸F-FDG-PET/CT in this setting.

Summary

¹⁸F-FDG-PET/CT has proven its high diagnostic value for the detection of peripheral emboli in patients with infective endocarditis and cardiac device infections, substantially affecting patients’ outcome and treatment. A multimodal approach, combining the high sensitivity of ¹⁸F-FDG-PET/CT with morphological imaging seems promising.

     

Supraventricular bigeminy originating from the mitral annulus: What is the mechanism?

We present a case of a 67‐year‐old female with a previous history of pulmonary vein isolation for paroxysmal atrial fibrillation who presented with supraventricular bigeminy with a constant coupling interval. The supraventricular bigeminy originated from the anterior mitral annulus with initial mapping suggestive of a focal mechanism. However detailed mapping using an ultrahigh resolution mapping system (with the manual shifting of the annotation window) revealed very low amplitude potentials connecting the previous sinus beat with continuous activation along the mitral annulus. Our observations were indicative of a re‐entry mechanism underlying the supraventricular bigeminy.     

Current status of lung transplantation

Lung transplantation is a well-established treatment option for selected patients with end-stage lung disease, leading to improved survival and improved quality of life. The last 20 years have seen a steady growth in number of lung transplantation procedures performed worldwide. The increase in clinical activity has been associated with tremendous progress in the understanding of cellular and molecular processes that limit both short- and long-term outcomes. This review gives a comprehensive overview of the current status of lung transplantation for the referring physician. It demonstrates that careful selection of potential recipients, optimisation of their condition prior to transplant, use of carefully assessed donor organs, excellent surgery and meticulous long-term follow-up are all essential ingredients in determining a successful outcome.     

TNFα From Classically Activated Macrophages Accentuates Epithelial to Mesenchymal Transition in Obliterative Bronchiolitis

Bronchiolitis obliterans syndrome is characterized by fibrotic obliteration of small airways which severely impairs graft function and survival after lung transplantation. Bronchial epithelial cells from the transplanted lung can undergo epithelial to mesenchymal transition and this can be accentuated by activated macrophages. Macrophages demonstrate significant plasticity and change phenotype in response to their microenvironment. In this study we aimed to identify secretory products from macrophages that might be therapeutic targets for limiting the inflammatory accentuation of epithelial to mesenchymal transition in bronchiolitis obliterans syndrome. TNFα, IL‐1β and IL‐8 are elevated in bronchoalveolar lavage from lung transplant patients prior to diagnosis of bronchiolitis obliterans syndrome. Classically activated macrophages secrete more TNFα and IL‐1β than alternatively activated macrophages and dramatically accentuate TGF‐β1‐driven epithelial to mesenchymal transition in bronchial epithelial cells isolated from lung transplant patients. Blocking TNFα, but not IL‐1β, inhibits the accentuation of epithelial to mesenchymal transition. In a pilot unblinded therapeutic intervention in five patients with progressive bronchiolitis obliterans syndrome, anti‐TNFα treatment improved forced expiratory volume in 1 second and 6‐min walk distances in four patients. Our data identify TNFα as a potential new therapeutic target in bronchiolitis obliterans syndrome deserving of a randomized placebo controlled clinical trial.     

Pseudomonas aeruginosa Induced Airway Epithelial Injury Drives Fibroblast Activation: A Mechanism in Chronic Lung Allograft Dysfunction

Bacterial infections after lung transplantation cause airway epithelial injury and are associated with an increased risk of developing bronchiolitis obliterans syndrome. The damaged epithelium is a source of alarmins that activate the innate immune system, yet their ability to activate fibroblasts in the development of bronchiolitis obliterans syndrome has not been evaluated. Two epithelial alarmins were measured longitudinally in bronchoalveolar lavages from lung transplant recipients who developed bronchiolitis obliterans syndrome and were compared to stable controls. In addition, conditioned media from human airway epithelial cells infected with Pseudomonas aeruginosa was applied to lung fibroblasts and inflammatory responses were determined. Interleukin‐1 alpha (IL‐1α) was increased in bronchoalveolar lavage of lung transplant recipients growing P. aeruginosa (11.5 [5.4–21.8] vs. 2.8 [0.9–9.4] pg/mL, p < 0.01) and was significantly elevated within 3 months of developing bronchiolitis obliterans syndrome (8.3 [1.4–25.1] vs. 3.6 [0.6–17.1] pg/mL, p < 0.01), whereas high mobility group protein B1 remained unchanged. IL‐1α positively correlated with elevated bronchoalveolar lavage IL‐8 levels (r² = 0.6095, p < 0.0001) and neutrophil percentage (r² = 0.25, p = 0.01). Conditioned media from P. aeruginosa infected epithelial cells induced a potent pro‐inflammatory phenotype in fibroblasts via an IL‐1α/IL‐1R‐dependent signaling pathway. In conclusion, we propose that IL‐1α may be a novel therapeutic target to limit Pseudomonas associated allograft injury after lung transplantation.     

Cyclooxygenase (COX) 1 and 2 in normal, inflamed, and ulcerated human gastric mucosa

BACKGROUND AND AIMS: Constitutive cyclooxygenase (COX) 1 is believed to mediate prostaglandin dependent gastric protection. However, gastric mucosa contains cells capable of expressing inducible COX-2. We therefore investigated COX-1 and COX-2 expression, localisation, and activity in normal and abnormal human gastric mucosa. METHODS: COX-1 and COX-2 distribution was investigated by light and electron microscopic immunohistochemistry and by western blot analysis, and their contribution to prostaglandin (PG)E(2) synthesis using selective enzyme inhibitors. RESULTS: There was strong parietal cell COX-1 and COX-2 immunoreactivity in all sections and isolated cells, with macrophage and myofibroblast reactivity in some sections. Immunostaining was specifically abolished by antigen absorption. Western blot analysis confirmed COX-1 and 2 expression. COX-1 and COX-2 immunostaining was increased in Helicobacter pylori gastritis, particularly the mid glandular zone and lamina propria inflammatory cells. This was associated with increased ex vivo PGE(2) synthesis (62.4 (13.5) pg/mg v 36.3 (15.5) pg/mg in uninflamed mucosa; p=0. 017) which was significantly inhibited by COX-1 but not COX-2 inhibition. Increased COX-2 immunostaining in macrophages, endothelial cells, and myofibroblasts (with reduced epithelial expression) was seen at the rim of ulcers. CONCLUSION: COX-2, as well as COX-1, is expressed by normal human gastric mucosa and is increased at the rim of ulcers. Although both are increased with H pylori, COX-1 contributes more than COX-2 to gastric PGE(2) production.