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Background Sepsis is a life-threatening condition that requires immediate focus identification and control. However, international sepsis guidelines do not provide information on imaging choice. Purpose To identify predictors of CT findings and patient outcomes in a population of septic patients from a medical ICU. Material and methods A full-text search in the radiological information system (RIS) retrieved 227 body CT examinations conducted to identify infectious sources in 2018. CT reports were categorized according to identified foci and their diagnostic certainty. Diagnostic accuracy of CT was compared to microbiological results. Clinical and laboratory information was gathered. Statistical analysis was performed using nonparametric tests and logistic regression analysis. Results CT revealed more positive infectious foci 52.4% (n = 191/227) than microbiological tests 39.3% (n = 79/201). There were no significant differences between focus-positive CT scans with regard to positive microbiological testing (p = 0.32). Sequential organ failure assessment (SOFA) scores were slightly but nonsignificantly higher in patients with a focus-positive CT, odds ratio (OR) = 0.999 (95% CI 0.997–1.001) with p = 0.52. Among C-reactive protein (CRP), procalcitonin (PCT), and leukocytes, in focus-positive versus focus-negative CT scans, CRP showed a minor but statistically significant elevation in the group with focus-positive CT scans (OR = 1.004, 95% CI = 1.000–1.007, p = 0.04). No significant association was found for PCT (OR = 1.007, 95% CI = 0.991–1.023; p = 0.40) or leukocytes (OR = 1.003, 95% CI = 0.970–1.038; p = 0.85). In 33.5% (n = 76/227) of cases, the CT findings had at least one therapeutic consequence. In 81.6% (n = 62/76), the CT findings resulted in one consequence, in 14.5% (n = 11/76) in two consequences, and in 3.9% (n = 3/76) in three consequences. There was no significant association between focus-positive CT scans and mortality (p = 0.81). Conclusion In this population of septic patients in medical intensive care, microbiological analysis complemented CT findings. Both clinical and laboratory parameters were not predictive of CT findings. While therapeutic consequences of CT findings in this study population underline the role of CT for decision making in septic patients, CT findings do not predict patient outcomes in this retrospective analysis.

Purpose: This study aimed at retrospectively evaluating full-body computed tomography (CT) examinations for the prevalence of cerebrovascular events in patients with suspected sepsis treated in the intensive care unit (ICU). Methods: All full-body CT examinations, i.e., both cranial CT (cCT) and body CT including chest, abdomen and pelvis, for focus search in septic patients over a 12-months period were identified from three ICUs, using full-text search. From this retrospective cohort, we fully analyzed 278 cCT examinations for the occurrence of acute cerebral findings. All acute cerebrovascular events were independently reviewed by two blinded readers. Clinical and laboratory findings were extracted. The data were statistically analyzed using contingency tests. Results: In our population of patients with suspected sepsis, 10.8% (n = 30/278) were identified to have major cerebral events, including 7.2% (n = 20/278) major cerebrovascular events and 4.3% (n = 12/278) generalized parenchymal damage. 13.4% (n = 22/163) of patients with a severe coma as compared with non-severe coma, 4.4% (n = 3/68), showed a major cerebral event (p = 0.04). Patients referred from the cardiology/nephrology ICU ward showed major cerebral events in 16.3% (n = 22/135), as compared with 4.9% (n = 3/61) in patients from pulmonary ICU and 6.1% (n = 5/82) major cerebral events with surgical referral (p = 0.02). Conclusion: Our study provides further evidence that septic patients may suffer from cerebral events with relevance to their prognosis. Severe coma and the referring ward were associated with acute cerebral conditions. Full-body CT has the advantage of both detecting of septic foci and possibly identifying ischemic or hemorrhagic stroke in this vulnerable patient population.

Objective Patients with severe infection or sepsis require fast identification of the focus and prompt eradication. This study aims at investigating the role of body computed tomography (CT) and identifying outcome predictors in a general ward setting of patients with obscure infection. Methods We retrospectively identified 196 consecutive body CTs acquired in 179 patients with obscure infection, i.e. severe infection or sepsis from general wards with unclear focus, over 12-months in the year 2018. Reports were extracted using a full-text search in the radiological information system (RIS) of a large university medical center. CT reports were classified according to diagnostic confidence of the reader (i.e. certain, likely, possible, no focus), and correlated with clinical and laboratory parameters. The discharge diagnosis was set as the diagnostic reference standard. Contingency tables were prepared for statistical analysis with Chi-squared test amongst other analyses and the calculation of AUC statistics. Results In 133 out of 196 (67.9 %) body CTs from general wards with severe infection or sepsis, body CT identified an infectious focus. 90 % of the infections were located in the chest, abdomen, and genitourinary tract, in descending order. In 76.5 % (150 of 196) of examinations, CT correctly predicted the final infectious source. The positive predictive value (PPV) of a CT-detected focus was 84.2 % (95 % CI 79.0%–88.3%). A high diagnostic confidence of the reader resulted in a PPV of 96.4 % (95 % CI 87.4%–99.1%) while a low confidence resulted in a PPV of 63.3 % (95 % CI 48.2%–76.3%). Conclusion In patients with obscure infection treated in general wards, body CT detects the infectious source with a high positive predictive value. Focus detection accuracy highly depends on the diagnostic confidence of the CT reader.

Objective Sepsis is defined as organ dysfunction due to severe infection. Septic patients face a significant mortality risk. Thus, timely recognition with prompt focus identification and control are essential. This study aims to determine the current role of computed tomography (CT) in the diagnostic workup of septic patients. Methods We retrospectively identified 357 patients in the emergency department (ED) of a large university center with suspected sepsis in a two-year period. A total of 132 patients underwent CT scanning within 72 h of admission. Patients were characterized by clinical and laboratory findings. CT reports were categorized and matched with clinical data. Results Of 357 ED patients with suspected sepsis, 37.0% (132/357) underwent CT imaging within 72 h. The most commonly identified septic foci in CT were chest 38.6% (49/127), abdomen 22.0% (28/127) and genitourinary tract 20.5% (26/127) in descending order. The focus detection rate was 76.5% per patient with a concurrent number-needed-to-scan of 1.31. Contrast medium administration in CT did not improve focus detection rate (p = 0.631) or diagnostic confidence in this patient population (p = 0.432). CT had a positive predictive value of 81.82% (CI 76.31 to 86.28%) in predicting the focus of the discharge diagnosis. Follow-up imaging in patients with unclear focus reveals a new focus in 39.5% of patients. Conclusions Our investigation of the role of CT in ED patients with suspected sepsis indicated a high positive predictive value for CT with regard to the discharge diagnosis. Repeat imaging may help identify further septic foci in a subgroup with persistently unclear focus. Use of contrast medium seems less relevant for focus detection than expected, as it did not increase diagnostic confidence.

Mesenchymal stromal cells (MSCs) are crucial components of the bone marrow (BM) microenvironment essential for regulating self-renewal, survival, and differentiation of hematopoietic stem/progenitor cells (HSPCs) in the stem cell niche. MSCs are functionally altered in myelodysplastic syndromes (MDS) and exhibit an altered methylome compared with MSCs from healthy controls, thus contributing to disease progression. To determine whether MSCs are amenable to epigenetic therapy and if this affects their function, we examined growth, differentiation, and HSPC-supporting capacity of ex vivo–expanded MSCs from MDS patients in comparison with age-matched healthy controls after direct treatment in vitro with the hypomethylating agent azacitidine (AZA). Strikingly, we find that AZA exerts a direct effect on healthy as well as MDS-derived MSCs such that they favor support of healthy over malignant clonal HSPC expansion in coculture experiments. RNA-sequencing analyses of MSCs identified stromal networks regulated by AZA. Notably, these comprise distinct molecular pathways crucial for HSPC support, foremost extracellular matrix molecules (including collagens) and interferon pathway components. Our study demonstrates that the hypomethylating agent AZA exerts its antileukemic activity in part through a direct effect on the HSPC-supporting BM niche and provides proof of concept for the therapeutic potential of epigenetic treatment of diseased MSCs. In addition, our comprehensive data set of AZA-sensitive gene networks represents a valuable framework to guide future development of targeted epigenetic niche therapy in myeloid malignancies such as MDS and acute myeloid leukemia.