Long-lasting impairment of the immune system is believed to be the underlying reason for delayed deaths after surviving sepsis. We tested the hypothesis of persisting changes to the immune system in survivors of sepsis for the first time. In our prospective, cross-sectional pilot study, eight former patients who survived catecholamine-dependent sepsis and eight control individuals matched for age, sex, diabetes and renal insufficiency were enrolled. Each participant completed a questionnaire concerning morbidities, medications and infection history. Peripheral blood was collected for determination of i) immune cell subsets (CD4+, CD8+ T cells; CD25+ CD127- regulatory T cells; CD14+ monocytes), ii) cell surface receptor expression (PD-1, BTLA, TLR2, TLR4, TLR5, Dectin-1, PD-1 L), iii) HLA-DR expression, and iv) cytokine secretion (IL-6, IL10, TNF-α, IFN-γ) of whole blood stimulated with either α-CD3/28, LPS or zymosan. After surviving sepsis, former patients presented with increased numbers of clinical apparent infections, including those typically associated with an impaired immune system. Standard inflammatory markers indicated a low-level inflammatory situation in former sepsis patients. CD8+ cell surface receptor as well as monocytic HLA-DR density measurements showed no major differences between the groups, while CD4+ T cells tended towards two opposed mechanisms of negative immune cell regulation via PD-1 and BTLA. Moreover, the post-sepsis group showed alterations in monocyte surface expression of distinct pattern recognition receptors; most pronouncedly seen in a decrease of TLR5 expression. Cytokine secretion in response to important activators of both the innate (LPS, zymosan) and the adaptive immune system (α-CD3/28) seemed to be weakened in former septic patients. Cytokine secretion as a reaction to different activators of the immune system seemed to be comprehensively impaired in survivors of sepsis. Among others, this could be based on trends in the downregulation of distinct cell surface receptors. Based on our results, the conduct of larger validation studies seems feasible, aiming to characterize alterations and to find potential therapeutic targets to engage.

Intraoperative hypotension is associated with acute kidney injury (AKI). Clinicians thus frequently use vasopressors, such as norepinephrine, to maintain blood pressure. However, vasopressors themselves might promote AKI. We sought to determine whether both intraoperative hypotension and cumulative intraoperative norepinephrine dose are independently associated with postoperative AKI in patients undergoing noncardiac surgery. This was a retrospective cohort analysis of 38 338 adult male and female patients who had noncardiac surgery. The primary outcome was AKI within the first 7 postoperative days. We performed adjusted multivariable logistic regression analysis to determine whether intraoperative hypotension (quantified as area under a mean arterial pressure [MAP] of 65 mm Hg) and cumulative intraoperative norepinephrine dose were independently associated with AKI. The median (25th percentile, 75th percentile) area under a MAP of 65 mm Hg was 0.09 (0.02, 0.22) mm Hg∗day in patients with AKI and 0.05 (0.01, 0.14) mm Hg∗day in patients without AKI (P<0.001). The cumulative intraoperative norepinephrine dose was 1.92 (0.00, 13.09) μg kg^-1 in patients with AKI and 0.00 (0.00, 0.00) μg kg^-1 in patients without AKI (P<0.001). Both the area under a MAP of 65 mm Hg (odds ratio 1.55 [95% confidence interval 1.17-2.02] per mm Hg∗day; P=0.002) and the cumulative intraoperative norepinephrine dose (odds ratio 1.02 [95% confidence interval 1.01-1.02] per μg kg^-1; P<0.001) were independently associated with AKI. Both intraoperative hypotension and cumulative intraoperative norepinephrine dose were independently associated with postoperative AKI in patients undergoing noncardiac surgery. Pending results of trials testing whether these relationships are causal, it seems prudent to avoid both profound hypotension and high norepinephrine doses in adults undergoing noncardiac surgery.

Electrochemiluminescence (ECL) has an inherently low background and enables precise chemical reactions through electrical control. Here, we report an advanced ECL system, termed ECLipse (ECL in paired signal electrode). We physically separated ECL generation from target detection: These two processes were carried out in isolated chambers and coupled through an electrode. The strategy allowed us to minimize cross-chemical reactions, design electrodes for high ECL signals, and integrate multiple sensors in a chip. As a proof of concept, we implemented an eight-plex ECLipse and applied it to detect host factors in human plasma. ECLipse achieved higher signal-to-noise ratio than conventional ECL assays and was >7000-fold more sensitive than enzyme-linked immunosorbent assay. In a pilot clinical study, we could detect septic conditions by measuring host factors [i.e., interleukin-3 (IL-3), IL-6, and procalcitonin (PCT)]. ECLipse assay further revealed distinct IL-3 and IL-6 patterns in patients with severe acute respiratory syndrome coronavirus 2 infection.

Major surgery is regularly associated with clinical signs of systemic inflammation, which potentially affects the rapid identification of sepsis. Therefore, this secondary analysis of an observational study aims to determine whether NADH dehydrogenase 1 (ND1) mitochondrial DNA (mtDNA) could be used as a potential biomarker for the discrimination between septic shock and postsurgical systemic inflammation. Overall, 80 patients were included (septic shock (n = 20), cardiac artery bypass grafting (CABG, n = 20), major abdominal surgery (MAS, n = 20), and matched controls (CTRL, n = 20)). Quantitative PCR was performed to measure ND1 mtDNA. Thromboelastography was used to analyze the coagulatory system. Free-circulating ND1 mtDNA levels were significantly higher in septic shock patients compared to patients suffering from post-surgical inflammation ({copies/µL}: CTRL: 1208 (668–2685); septic shock: 3823 (2170–7318); CABG: 1272 (417–2720); and MAS: 1356 (694–2845); CTRL vs. septic shock: p < 0.001; septic shock vs. CABG: p < 0.001; septic shock vs. MAS: p = 0.006; CABG vs. MAS: p = 0.01). ND1 mtDNA levels in CABG patients showed a strong positive correlation with fibrinogen (correlation coefficient [r]= 0.57, p < 0.001) and fibrinogen-dependent thromboelastographic assays (maximum clot firmness, EXTEM: r = 0.35, p = 0.01; INTEM: r = 0.31, p = 0.02; FIBTEM: r = 0.46, p < 0.001). In conclusion, plasma levels of free-circulating ND1 mtDNA were increased in septic shock patients and were discriminative between sepsis and surgery-induced inflammation. Furthermore, this study showed an association between ND1 mtDNA and a fibrinogen-dependent pro-coagulatory shift in cardiac surgical patients.

The aim of this study was to investigate whether goal-directed treatment using artificial intelligence, compared to standard care, can reduce the frequency, duration, and severity of intraoperative hypotension in patients undergoing single lung ventilation, with a potential reduction of postoperative acute kidney injury (AKI). single center, single-blinded randomized controlled trial. University hospital operating room. 150 patients undergoing lung surgery with single lung ventilation were included. Patients were randomly assigned to two groups: the Intervention group, where a goal-directed therapy based on the Hypotension Prediction Index (HPI) was implemented; the Control group, without a specific hemodynamic protocol. The primary outcome measures include the frequency, duration of intraoperative hypotension, furthermore the Area under MAP 65 and the time-weighted average (TWA) of MAP of 65. Other outcome parameters are the incidence of AKI and myocardial injury after non-cardiac surgery (MINS). The number of hypotensive episodes was lower in the intervention group compared to the control group (0 [0-1] vs. 1 [0-2]; p = 0.01), the duration of hypotension was shorter in the intervention group (0 min [0-3.17] vs. 2.33 min [0-7.42]; p = 0.01). The area under the MAP of 65 (0 mmHg * min [0-12] vs. 10.67 mmHg * min [0-44.16]; p < 0.01) and the TWA of MAP of 65 (0 mmHg [0-0.08] vs. 0.07 mmHg [0-0.25]; p < 0.01) were lower in the intervention group. The incidence of postoperative AKI showed no differences between the groups (6.7 % vs.4.2 %; p = 0.72). There was a trend to lower incidence of MINS in the intervention group (17.1 % vs. 31.8 %; p = 0.07). A tendency towards reduced postoperative infection was seen in the intervention group (16.0 % vs. 26.8 %; p = 0.16). The implementation of a treatment algorithm based on HPI allowed us to decrease the duration and severity of hypotension in patients undergoing lung surgery. It did not result in a significant reduction in the incidence of AKI, however we observed a tendency towards lower incidence of MINS in the intervention group, along with a slight reduction in postoperative infections.