Metastatic infection is an important complication of bacteremia (SAB). Early diagnosis of metastatic infection is crucial, because specific treatment is required. However, metastatic infection can be asymptomatic and difficult to detect. In this study, we investigated the role ofF-FDG PET/CT in patients with SAB for detection of metastatic infection and its consequences for treatment and outcome. All patients with SAB at Radboud University Medical Center were included between January 2013 and April 2016. Clinical data and results ofF-FDG PET/CT and other imaging techniques, including echocardiography, were collected. Primary outcomes were newly diagnosed metastatic infection by F-FDG PET/CT, subsequent treatment modifications, and patient outcome. A total of 184 patients were included, and F-FDG PET/CT was performed in 105 patients, of whom 99 had a high-risk bacteremia.F-FDG PET/CT detected metastatic infectious foci in 73.7% of these high-risk patients. In 71.2% of patients with metastatic infection, no signs and symptoms suggesting metastatic complications were present before F-FDG PET/CT was performed.F-FDG PET/CT led to a total of 104 treatment modifications in 74 patients. Three-month mortality was higher in high-risk bacteremia patients without F-FDG PET/CT performed than in those in whomF-FDG PET/CT was performed (32.7% vs. 12.4%, = 0.003). In multivariate analysis,F-FDG PET/CT was the only factor independently associated with reduced mortality ( = 0.005; odds ratio, 0.204; 95% confidence interval, 0.066-0.624). A higher comorbidity score was independently associated with increased mortality ( = 0.003; odds ratio, 1.254; 95% confidence interval, 1.078-1.457). F-FDG PET/CT is a valuable technique for early detection of metastatic infectious foci, often leading to treatment modification. PerformingF-FDG PET/CT is associated with significantly reduced 3-mo mortality.

Background Excessive activation of immune responses in coronavirus disease 2019 (COVID-19) is considered to be related to disease severity, complications and mortality. The complement system is an important component of innate immunity and can stimulate inflammation, but its role in COVID-19 is unknown. Methods A prospective, longitudinal, single center study was performed in hospitalized COVID-19 patients. Plasma concentrations of complement factors C3a, C3c, and terminal complement complex (TCC) were assessed at baseline and during hospital admission. In parallel, routine laboratory and clinical parameters were collected from medical files and analyzed. Results Complement factors C3a, C3c and TCC were significantly increased in plasma of COVID-19 patients compared to healthy controls (p<0.05). These complement factors were especially elevated in ICU patients during the entire disease course (p<0.005 for C3a and TCC). More intense complement activation was observed in patients that deceased and in patients with thromboembolic events. Conclusions COVID-19 patients demonstrate activation of the complement system, which is related to disease severity. This pathway may be involved in the dysregulated pro-inflammatory response associated with increased mortality and thromboembolic complications. Components of the complement system might have potential as prognostic markers for disease severity and as therapeutic targets in COVID-19.

PurposeThe aim of this study was to determine the diagnostic value of 18F–fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET/CT) and magnetic resonance imaging (MRI) in diagnosing vertebral osteomyelitis.MethodsFrom November 2015 until December 2016, 32 patients with suspected vertebral osteomyelitis were prospectively included. All patients underwent both 18F–FDG-PET/CT and MRI within 48 h. All images were independently reevaluated by two radiologists and two nuclear medicine physicians who were blinded to each others’ image interpretation. 18F–FDG-PET/CT and MRI were compared to the clinical diagnosis according to international guidelines.ResultsFor 18F–FDG-PET/CT, sensitivity, specificity, PPV, and NPV in diagnosing vertebral osteomyelitis were 100%, 83.3%, 90.9%, and 100%, respectively. For MRI, sensitivity, specificity, PPV, and NPV were 100%, 91.7%, 95.2%, and 100%, respectively. MRI detected more epidural/spinal abscesses. An important advantage of 18F–FDG-PET/CT is the detection of metastatic infection (16 patients, 50.0%).Conclusion 18F–FDG-PET/CT and MRI are both necessary techniques in diagnosing vertebral osteomyelitis. An important advantage of 18F–FDG-PET/CT is the visualization of metastatic infection, especially in patients with bacteremia. MRI is more sensitive in detection of small epidural abscesses.

The clinical spectrum of COVID-19 varies and the differences in host response characterizing this variation have not been fully elucidated. COVID-19 disease severity correlates with an excessive pro-inflammatory immune response and profound lymphopenia. Inflammatory responses according to disease severity were explored by plasma cytokine measurements and proteomics analysis in 147 COVID-19 patients. Furthermore, peripheral blood mononuclear cell cytokine production assays and whole blood flow cytometry were performed. Results confirm a hyperinflammatory innate immune state, while highlighting hepatocyte growth factor and stem cell factor as potential biomarkers for disease severity. Clustering analysis reveals no specific inflammatory endotypes in COVID-19 patients. Functional assays reveal abrogated adaptive cytokine production (interferon-gamma, interleukin-17 and interleukin-22) and prominent T cell exhaustion in critically ill patients, whereas innate immune responses were intact or hyperresponsive. Collectively, this extensive analysis provides a comprehensive insight into the pathobiology of severe to critical COVID-19 and highlight potential biomarkers of disease severity.

PurposeThe purpose of this study was to evaluate the diagnostic value of 18F-fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET/CT scan) and magnetic resonance imaging (MRI) in diagnosing spondylodiscitis and its complications, such as epidural and paraspinal abscesses.MethodsFrom January 2006 to August 2013 patients with a clinical suspicion of spondylodiscitis, with an infection, or with fever of unknown origin were retrospectively included if 18F-FDG-PET/CT and MRI of the spine were performed within a 2-week time span. Imaging results were compared to the final clinical diagnosis and follow-up data were collected.ResultsSixty-eight patients were included of whom 49 patients were diagnosed with spondylodiscitis. MRI showed an overall sensitivity of 67 % and specificity of 84 %. Diagnostic accuracy was 58 %, when MRI was performed within 2 weeks after the start of symptoms and improved to 82 %, when performed more than 2 weeks after onset of symptoms. 18F-FDG-PET/CT showed a sensitivity of 96 % and a specificity of 95 %, with no relation to the interval between the scan and the start of symptoms.ConclusionsAs compared to MRI, 18F-FDG-PET/CT has superior diagnostic value for detecting early spondylodiscitis. After 2 weeks both techniques perform similarly.

Fever of unknown origin (FUO) is commonly defined as fever higher than 38.3°C on several occasions during at least 3 weeks with uncertain diagnosis after a number of obligatory investigations. The differential diagnosis of FUO can be subdivided in four categories: infections, malignancies, noninfectious inflammatory diseases, and miscellaneous causes. In most cases of FUO, there is an uncommon presentation of a common disease. FDG-PET/CT is a sensitive diagnostic technique for the evaluation of FUO by facilitating anatomical localization of focally increased FDG uptake, thereby guiding further diagnostic tests to achieve a final diagnosis. FDG-PET/CT should become a routine procedure in the workup of FUO when diagnostic clues are absent. FDG-PET/CT appears to be a cost-effective routine imaging technique in FUO by avoiding unnecessary investigations and reducing the duration of hospitalization.

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matched controls, only 3 (17%) showed a spontaneous reduction in oxygen supplementation of 3 L/min or greater within 24 hours. We noted that in 3 patients treated with icatibant there was a resurgence in the need for oxygen supplementation. Icatibant treatment was well tolerated in all 10 patients who received the drug. There were no severe adverse events. There was no clear association with D-dimer concentrations and fever. Discussion This study found evidence of an association between receipt of icatibant and improved oxygenation, suggesting that targeting the kallikrein-kinin system in patients with COVID-19, especially in the early stages of disease when patients are hypoxic and are admitted to the hospital, might be beneficial. An important limitation of the current study is that it is exploratory and not a randomized clinical trial. The observed resurgence of oxygen need in some patients after icatibant may be due to icatibant's short half life of about 2 hours. 3 We propose that treatment strategies targeting the kallikrein-kinin system should be investigated in randomized trials for patients with COVID-19.