Die Computertomographie zur Detektion von Infektfoci bei hospitalisierten Patient:innen mit Sepsis: Status quo der klinischen Versorgung und Ansätze zur Optimierung

In dieser Arbeit wurde die Rolle der Computertomographie (CT) zur Detektion von Infektquellen bei Patient:innen mit Sepsis untersucht. Die vorliegende Arbeit charakterisiert zunächst den aktuellen Stand der Diagnostik septischer Patient:innen mittels CT-Bildgebung. Die CT wird auf Basis der durchgeführten Untersuchungen als relevantes diagnostisches Verfahren zur Infektfokussuche bestätigt, das bspw. durch die Mikrobiologie komplementiert wird. Für unterschiedliche Settings wie die Rettungsstelle, die Normalstation und die Intensivstation konnte die wenige verfügbare Literatur ergänzt werden um Informationen zur Häufigkeitsverteilung bildgebend detektierter Infektfoci. Weiterhin konnte ermittelt werden, dass eine klinische und/oder auf Basis von Laborwerten generierte Einschätzung in allen untersuchten Settings nicht hinreichend prädiktiv für das Auftreten eines im CT detektierbaren Infektfokus ist. Es wurde festgestellt, dass sich in Abhängigkeit von der CT-Befundsicherheit vorhersagen lässt, ob die im CT registrierten Infektfoci den finale Foci, d.h. den im Arztbrief angegebenen Entlassdiagnosen, entsprechen. In einem relevanten Anteil der Patient:innen mit nachgewiesenem Infektfokus wurden zudem therapeutische Konsequenzen identifiziert, die sich auf die Diagnostik zurückführen ließen. In den Studien wurden die Morbidität und die Mortalität von Patient:innen mit Sepsis unter Berücksichtigung der CT-Bildgebung ausführlich untersucht und assoziierte Faktoren beschrieben. Um prognostisch relevante bildgebende Faktoren zu charakterisieren, untersuchten wir außerdem cerebrovaskuläre Ereignisse, die bei Patient:innen mit Sepsis gehäuft auftreten. Dabei konnten wir erstmalig die Prävalenz cerebrovaskulärer Ereignisse bei Sepsis beschreiben und die Relevanz für das Patient:innen-Outcome analysieren. Ein weiterer wichtiger Schritt in der vorliegenden Arbeit war die Untersuchung der Qualität der bildgebenden Diagnostik von Patient:innen der Intensivstation. Hierbei konnte der Nutzen des interdisziplinären Austauschs in MDCs mit strukturiertem Feedback gezeigt werden. So stellten wir eine Reduktion des Auftretens von QM-Ereignissen fest nach Einführung eines neuen, regelmäßigen und strukturierten Konferenzformats

Pseudo aneurysm of the uterine artery with arteriovenous fistula after cesarean section: A rare but sinister cause of delayed postpartum hemorrhage

Pseudoaneurysm of the uterine artery is a rare complication of cesarean section. Delayed diagnosis and management may result in rapid and catastrophic postpartum hemorrhage and may necessitate hysterectomy or can even be fatal. A 28-year-old woman (gravida I, para I) presented with delayed postpartum hemorrhage 10 days after emergency cesarean section. Using transabdominal and transvaginal Color Doppler sonography, we detected a pseudoaneurysm in the posterior uterine wall, which was successfully treated with selective embolization distal and proximal to the lesion with platinum coils. In patients with delayed postpartum hemorrhage-especially after cesarean section-the rare possibility of uterine artery pseudoaneurysm must be kept in mind

Analyzing nicotinamide adenine dinucleotide phosphate oxidase activation in aging and vascular amyloid pathology

In aging individuals, both protective as well as regulatory immune functions are declining, resulting in an increased susceptibility to infections as well as to autoimmunity. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2-deficiency in immune cell subsets has been shown to be associated with aging. Using intravital marker-free NAD(P)H-fluorescence lifetime imaging, we have previously identified microglia/myeloid cells and astrocytes as main cellular sources of NADPH oxidase (NOX) activity in the CNS during neuroinflammation, due to an overactivation of NOX. The overactivated NOX enzymes catalyze the massive production of the highly reactive O−2, which initiates in a chain reaction the overproduction of diverse reactive oxygen species (ROS). Age-dependent oxidative distress levels in the brain and their cellular sources are not known. Furthermore, it is unclear whether in age- dependent diseases oxidative distress is initiated by overproduction of ROS or by a decrease in antioxidant capacity, subsequently leading to neurodegeneration in the CNS. Here, we compare the activation level of NOX enzymes in the cerebral cortex of young and aged mice as well as in a model of vascular amyloid pathology. Despite the fact that a striking change in the morphology of microglia can be detected between young and aged individuals, we find comparable low-level NOX activation both in young and old mice. In contrast, aged mice with the human APPE693Q mutation, a model for cerebral amyloid angiopathy (CAA), displayed increased focal NOX overactivation in the brain cortex, especially in tissue areas around the vessels. Despite activated morphology in microglia, NOX overactivation was detected only in a small fraction of these cells, in contrast to other pathologies with overt inflammation as experimental autoimmune encephalomyelitis (EAE) or glioblastoma. Similar to these pathologies, the astrocytes majorly contribute to the NOX overactivation in the brain cortex during CAA. Together, these findings emphasize the role of other cellular sources of activated NOX than phagocytes not only during EAE but also in models of amyloid pathology. Moreover, they may strengthen the hypothesis that microglia/monocytes show a diminished potential for clearance of amyloid beta protein

Successful aspiration thrombectomy in a patient with submassive, intermediate-risk pulmonary embolism following COVID-19 pneumonia

A 64-year-old female patient presented with severe dyspnea shortly after apparent recovery from COVID-19 disease. Chest computed tomography revealed central pulmonary embolism and ultrasonography showed a deep vein thrombosis of her right leg. The patient was tachycardiac with evidence of right ventricular strain on echocardiography. An interdisciplinary decision for interventional therapy was made. Angiographic aspiration thrombectomy resulted in a significant reduction of thrombus material and improved flow in the pulmonary arteries and immediate marked clinical improvement and subsequent normalization of functional echocardiographic parameters. This case adds to the emerging evidence for severe thromboembolic complications following COVID-19 and suggests aspiration thrombectomy can be considered in pulmonary embolism of intermediate risk

Age-dependent microstructural changes of the intervertebral disc: a validation of proteoglycan-sensitive spectral CT

Objective: To analyze the two major components of the intervertebral disc (IVD) in an ex vivo phantom, as well as age-related changes in patients. Methods: Collagen and chondroitin sulfate were imaged at different concentrations in agar solution. Age-related changes in disc density were retrospectively analyzed in normal-appearing discs in dual-energy computed tomography (DECT) images from a patient cohort with various spinal pathologies (n = 136). All computed tomography (CT) scans were acquired using single-source DECT at 80 and 135 kVp with automatic exposure calculation. In 136 patients, the attenuation of normal-appearing discs on collagen/chondroitin maps (cMaps) correlated with the patients' age with Pearson's r using standardized regions of interest in the anterior anulus fibrosus (AAF) and nucleus pulposus (NP). Results: DECT collagen mapping revealed concentration-dependent Hounsfield units (HU) of IVD components. For collagen, we found Pearson's r = 0.9610 (95% CI 0.6789-0.9959), p = 0.0023 at 120 kVe, and r = 0.8824 (95% CI 0.2495-0.9871), p = 0.0199 in cMap. For chondroitin sulfate, Pearson's r was 0.9583 (95% CI 0.6603-0.9956), p = 0.0026 at 120 kVp, and r = 0.9646 (95% CI 0.7044-0.9963), p = 0.0019 in cMap. Analysis of normal-appearing IVDs revealed an inverse correlation of density with age in the AAF: Pearson's r = - 0.2294 at 135 kVp (95% CI - 0.4012 to - 0.04203; p=0.0141) and r = - 0.09341 in cMap (95% CI - 0.2777 to 0.09754; p = 0.0003). In the NP, age and density did not correlate significantly at 135 kVp (p = 0.9228) and in cMap (p = 0.3229). Conclusions: DECT-based collagen mapping allows microstructural analysis of the two main intervertebral disc components-collagen and chondroitin sulfate. IVD density declines with age, presumably due to a reduction in collagen and chondroitin sulfate content. Age-related alterations of disc microstructure appear most pronounced in the AAF

Imaging intensive care patients: multidisciplinary conferences as a quality improvement initiative to reduce medical error

Background: Strategies to identify imaging-related error and minimise its consequences are important in the management of critically ill patients. A new quality management (QM) initiative for radiological examinations has been implemented in an intensive care unit (ICU) setting. In regular multidisciplinary conferences (MDCs), radiologists and ICU physicians re-evaluate recent examinations. Structured bilateral feedback is provided to identify errors early. This study aims at investigating its impact on the occurrence of QM events (imaging-related errors). Standardised protocols of all MDCs from 1st of June 2018 through 31st of December 2019 were analysed with regard to categories of QM events (i.e. indication, procedure, report) and resulting consequences. Results: We analysed 241 MDCs with a total of 973 examinations. 14.0% (n = 136/973) of examinations were affected by QM events. The majority of events were report-related (76.3%, n = 106/139, e.g. misinterpreted finding), followed by procedure-related (18.0%, n = 25/139, e.g. technical issue) and indication-related events (5.8%, n = 8/139, e.g. faulty indication). The median time until identification of a QM event (time to MDC) was 2 days (interquartile range = 2). Comparing the first to the second half of the intervention period, the incidence of QM events decreased significantly from 22.9% (n = 109/476) to 6.0% (n = 30/497) (p < 0.0001). Significance of this effect was confirmed by linear regression (p < 0.0001). Conclusions: Establishing structured discussion and feedback between radiologists and intensive care physicians in the form of MDCs is associated with a statistically significant reduction in QM events. These results indicate that MDCs may be one suitable approach to timely identify imaging-related error

Cerebrovascular Events in Suspected Sepsis: Retrospective Prevalence Study in Critically Ill Patients Undergoing Full-Body Computed Tomography

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

Body computed tomography in sepsis: predictors of CT findings and patient outcomes in a retrospective medical ICU cohort study

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

Tracking CNS and systemic sources of oxidative stress during the course of chronic neuroinflammation

The functional dynamics and cellular sources of oxidative stress are central to understanding MS pathogenesis but remain elusive, due to the lack of appropriate detection methods. Here we employ NAD(P)H fluorescence lifetime imaging to detect functional NADPH oxidases (NOX enzymes) in vivo to identify inflammatory monocytes, activated microglia, and astrocytes expressing NOX1 as major cellular sources of oxidative stress in the central nervous system of mice affected by experimental autoimmune encephalomyelitis (EAE). This directly affects neuronal function in vivo, indicated by sustained elevated neuronal calcium. The systemic involvement of oxidative stress is mirrored by overactivation of NOX enzymes in peripheral CD11b(+) cells in later phases of both MS and EAE. This effect is antagonized by systemic intake of the NOX inhibitor and anti-oxidant epigallocatechin-3-gallate. Together, this persistent hyper-activation of oxidative enzymes suggests an "oxidative stress memory" both in the periphery and CNS compartments, in chronic neuroinflammation

Overactivation of NADPH Oxidases – A pathophysiological correlate in Multiple Sclerosis?

In der Multiplen Sklerose sind Monozyten/Makrophagen als pathogenetisch relevante Immunzellen umfangreich beschrieben. Möglichweise leisten NADPH Oxidasen einen Beitrag zum Krankheitsgeschehen und dem Untergang von Nervenzellen, wobei deren Rolle bislang unklar ist. Die Aktivierung von NADPH Oxidasen lässt sich mit Fluorescence lifetime imaging microscopy (FLIM) direkt, d.h. Marker-frei auf molekularer Ebene visualisieren. In CD11b+ Monozyten aus dem Vollblut von Patienten mit Multipler Sklerose konnte so zum ersten Mal ein differenziertes Aktivierungsmuster in Abhängigkeit von der Krankheitsphase sowie der Therapie gezeigt werden. Zudem konnte der Effekt von Grünteeextrakt EGCG auf das Immunsystem genauer charakterisiert werden. Die Ergebnisse belegen einen Nutzen der Methode FLIM für das Monitoring entzündlicher Erkrankungen. Die detektierte Überaktivierung von NADPH Oxidasen in Multipler Sklerose impliziert neuartige Therapieansätze.The role of monocytes/macrophages in the course of the neuro-inflammatory disease multiple sclerosis has long been established. Though the definite mechanisms of damage to neurons were less obvious until recently. Potentially, NADPH oxidases are involved in the pathogenesis of multiple sclerosis. The activation of NADPH oxidases can now be visualized directly on a molecular level with a marker-free approach using Fluorescence lifetime imaging microscopy (FLIM). CD11b+ monocytes from whole-blood in multiple sclerosis reveal a distinctive pattern of activation depending on the phase and the therapy of the disease. Furthermore, the evaluation of the effect of green-tea extract EGCG on immune function provides a better insight in its potential actions in multiple sclerosis. The results point to a benefit of monitoring disease activity in inflammatory conditions with FLIM and hereby evaluate treatments. The overactivation of NOX enzymes warrants a new therapeutic approach in multiple sclerosis