Early detection, prevention and management of bacterial infections in the intensive care unit

Bacterial infections occur frequently in intensive care units (ICU) across the world. Their prevalence has relevant impacts on diagnostic approaches, patient treatment concepts and subsequent patient outcomes. In this habilitation, the role and manifestation of bacterial surface and device contamination potentially affecting critically ill patients with coronavirus disease 2019 (COVID-19) as well as appropriate diagnostic and management strategies with hospital epidemiological consequences during a novel pandemic are discussed. The work demonstrates that bacterial superinfections in critically ill COVID-19 patients with acute respiratory distress syndrome are frequent and commonly associated with longer duration of invasive mechanical ventilation. It highlights the substantial potential of structured microbiological sampling procedures and thorough antibiotic stewardship, in order to prevent the spread of multidrug resistant bacteria. Furthermore, potential benefits of the application of intravenous immunoglobulins as an early management strategy to treat necrotizing soft tissue infections (NSTI) are analyzed in a structured ICU patient cohort with a rare bacterial disease. To analyze a further specific management and prevention approach, this work characterizes the visual behaviour of critical care nurses while identifying drug labels of relevant ICU medications in a setting where performing under time pressure and the avoidance of medication errors - such as in patients with bacterial infections - are key. Together, the results of the presented work demonstrate the importance of accurate diagnostic, prevention and treatment strategies in the vulnerable collective of ICU patients with bacterial infections

EXCHANGE-2: investigating the efficacy of add-on plasma exchange as an adjunctive strategy against septic shock—a study protocol for a randomized, prospective, multicenter, open-label, controlled, parallel-group trial

Background Sepsis is as a life-threatening organ dysfunction caused by a dysregulated host response to an infection. The mortality of sepsis and particular of septic shock is very high. Treatment mostly focuses on infection control but a specific intervention that targets the underlying pathological host response is lacking to the present time. The investigators hypothesize that early therapeutic plasma exchange (TPE) will dampen the maladaptive host response by removing injurious mediators thereby limiting organ dysfunction and improving survival in patients with septic shock. Although small prospective studies demonstrated rapid hemodynamic stabilization under TPE, no adequately powered randomized clinical trial has investigated hard outcomes. Methods This is a randomized, prospective, multicenter, open-label, controlled, parallel-group interventional trial to test the adjunctive effect of TPE in patients with early septic shock. Patients with a refractory (defined as norepinephrine (NE) ≥ 0.4 μg/kg/min ≥ 30 min OR NE 0.3 μg/kg/min + vasopressin) and early (shock onset < 24 h) septic shock will be included. The intervention is a standard TPE with donor fresh frozen plasma (1.2 × individual plasma volume) performed within 6 h after randomization and will be compared to a standard of care (SOC) control arm. The primary endpoint is 28 days mortality for which the power analysis revealed a group size of 137 / arm (n = 274) to demonstrate a benefit of 15%. The key secondary objective will be to compare the extent of organ failure indicated by mean SOFA over the first 7 days as well as organ support-free days until day 28 following randomization. Besides numerous biological secondary, safety endpoints such as incidence of bleeding, allergic reactions, transfusion associated lung injury, severe thrombocytopenia, and other severe adverse events will be assessed during the first 7 days. For exploratory scientific analyses, biomaterial will be acquired longitudinally and multiple predefined scientific subprojects are planned. This study is an investigator-initiated trial supported by the German Research Foundation (DFG, DA 1209/7–1), in which 26 different centers in Germany, Switzerland, and Austria will participate over a duration of 33 months. Discussion This trial has substantial clinical relevance as it evaluates a promising adjunctive treatment option in refractory septic shock patients suffering from an extraordinary high mortality. A positive trial result could change the current standard of care for this septic subgroup. The results of this study will be disseminated through presentations at international congresses, workshops, and peer-reviewed publications. Trial registration ClinicalTrials.gov NCT05726825, Registered on 14 February 2023

A foreign older diabetic woman with an acute myocardial infarction: when cognitive biases in clinical decision-making become especially important

We present a case of an 80-year-old Turkish female patient with diabetes who suffered an acute myocardial infarction (AMI) and underwent percutaneous coronary balloon angioplasty (PTCA)/stenting. Due to new ischaemic episodes, a second PTCA/stenting had to be preformed 6 days later, which revealed a partial restent thrombosis. This case report raises several important issues. First, language problems are an important barrier for safety and quality in healthcare. Second, gender, ethnicity and age differences in patients with AMI need to be considered in order to eliminate inequities in clinical practice. Third, strategies to raise the awareness of cognitive biases as well as professional training about critical thinking and decision-making skills are needed

Still Standing Inside: A Local Idiom Related to Trauma among Namibian Speakers of Khoekhoegowab

Euro-centric psychiatric conceptualizations often ignore the interplay of local with universal factors in psychological suffering. Emic, locally focused perspectives can enrich etic knowledge to provide culturally sensitive care and to better elucidate the role of culture in mental illness. This study explored the idiom Tsûsa ǃNaeǃkhais xa hâǃnâ/mâǃnâ/ǂgâǃnâhe hâ (a terrible event has entered a person and remains standing inside), which was understood to relate to experiences of trauma and post-traumatic stress, among speakers of Khoekhoegowab, a southern-African click language. Semi-structured interviews were conducted with 16 participants from six urban and rural communities in Namibia. Questions probed perceptions of the idiom in terms of etiology, course, and risk and resilience factors from a socio-ecological framework. Five key themes were identified using thematic analysis: origin in a shocking event; intrusive recurrence of memories, “it keeps on coming back”; the close interplay between mental and physical suffering; the importance of active engagement in healing through prayer and acceptance; and the role of the community in both alleviating and amplifying distress. Our findings highlight local norms and strategies for adaptive coping, and the benefits of exploring local idioms to elucidate the braiding together of universal and cultural elements in psychological distress

Regulation of ICAM-1 in cells of the monocyte/macrophage system in microgravity

Cells of the immune system are highly sensitive to altered gravity, and the monocyte as well as the macrophage function is proven to be impaired under microgravity conditions. In our study, we investigated the surface expression of ICAM-1 protein and expression of ICAM-1 mRNA in cells of the monocyte/macrophage system in microgravity during clinostat, parabolic flight, sounding rocket, and orbital experiments. In murine BV-2 microglial cells, we detected a downregulation of ICAM-1 expression in clinorotation experiments and a rapid and reversible downregulation in the microgravity phase of parabolic flight experiments. In contrast, ICAM-1 expression increased in macrophage-like differentiated human U937 cells during the microgravity phase of parabolic flights and in long-term microgravity provided by a 2D clinostat or during the orbital SIMBOX/Shenzhou-8 mission. In nondifferentiated U937 cells, no effect of microgravity on ICAM-1 expression could be observed during parabolic flight experiments. We conclude that disturbed immune function in microgravity could be a consequence of ICAM-1 modulation in the monocyte/macrophage system, which in turn could have a strong impact on the interaction with T lymphocytes and cell migration. Thus, ICAM-1 can be considered as a rapid-reacting and sustained gravity-regulated molecule in mammalian cells