Transportable clock laser system with an instability of 1.6 × 10-16.

We present a transportable ultra-stable clock laser system based on a Fabry-Perot cavity with crystalline Al0.92Ga0.08As/GaAs mirror coatings, fused silica (FS) mirror substrates, and a 20 cm-long ultra-low expansion (ULE) glass spacer with a predicted thermal noise floor of mod σy = 7 × 10-17 in modified Allan deviation at one second averaging time. The cavity has a cylindrical shape and is mounted at 10 points. Its measured sensitivity of the fractional frequency to acceleration for the three Cartesian directions are 2(1) × 10-12 /(ms-2), 3(3) × 10-12 /(ms-2), and 3(1) × 10-12 /(ms-2), which belong to the lowest acceleration sensitivities published for transportable systems. The laser system's instability reaches down to mod σy = 1.6 × 10-16.

Thermal noise and mechanical loss of SiO2/Ta2O5 optical coatings at cryogenic temperatures.

Mechanical loss of dielectric mirror coatings sets fundamental limits for both gravitational wave detectors and cavity-stabilized optical local oscillators for atomic clocks. Two approaches are used to determine the mechanical loss: ringdown measurements of the coating quality factor and direct measurement of the coating thermal noise. Here we report a systematic study of the mirror thermal noise at 4, 16, 124, and 300 K by operating reference cavities at these temperatures. The directly measured thermal noise is used to extract the mechanical loss for SiO2/Ta2O5 coatings, which are compared with previously reported values.

Systematic analysis and comparison of commercial seizure-detection software.

OBJECTIVE: To determine if three different commercially available seizure-detection software packages (Besa 2.0, Encevis 1.7, and Persyst 13) accurately detect seizures with high sensitivity, high specificity, and short detection delay in epilepsy patients undergoing long-term video-electroencephalography (EEG) monitoring (VEM). METHODS: Comparison of sensitivity (detection rate), specificity (false alarm rate), and detection delay of three commercially available seizure-detection software packages in 81 randomly selected patients with epilepsy undergoing long-term VEM. RESULTS: Detection rates on a per-patient basis were not significantly different between Besa (mean 67.6%, range 0-100%), Encevis (77.8%, 0-100%) and Persyst (81%, 0-100%; P = .059). False alarm rate (per hour) was significantly different between Besa (mean 0.7/h, range 0.01-6.2/h), Encevis (0.2/h, 0.01-0.5/h), and Persyst (0.9/h, 0.04-6.5/h; P < .001). Detection delay was significantly different between Besa (mean 30 s, range 0-431 s), Encevis (25 s, 2-163 s), and Persyst (20 s, 0-167 s; P = .007). Kappa statistics showed moderate to substantial agreement between the reference standard and each seizure-detection software (Besa: 0.47, 95% confidence interval [CI] 0.36-0.59; Encevis: 0.59, 95% CI 0.47-0.7; Persyst: 0.63, 95% CI 0.51-0.74). SIGNIFICANCE: Three commercially available seizure-detection software packages showed similar, reasonable sensitivities on the same data set, but differed in false alarm rates and detection delay. Persyst 13 showed the highest detection rate and false alarm rate with the shortest detection delay, whereas Encevis 1.7 had a slightly lower sensitivity, the lowest false alarm rate, and longer detection delay.

Hyposmia Is Associated with Reduced Cognitive Function in COVID-19: First Preliminary Results.

BACKGROUND: Hyposmia is frequently reported as an initial symptom in coronavirus disease 2019 (COVID-19). OBJECTIVE: As hyposmia accompanies cognitive impairment in several neurological disorders, we aimed to study whether hyposmia represents a clinical biomarker for both neurological involvement and cognitive impairment in mild CO-VID-19. We aimed to study whether olfactory dysfunction (OD) represents a clinical biomarker for both neurological involvement and cognitive impairment in mild COVID-19. METHODS: Formal olfactory testing using the Sniffin'Sticks® Screening test, neuropsychological assessment using the Montreal Cognitive Assessment (MoCA), and detailed neurological examination were performed in 7 COVID-19 patients with mild disease course and no history of olfactory or cognitive impairment, and 7 controls matched for age, sex, and education. Controls were initially admitted to a dedicated COVID-19 screening ward but tested negative by real-time PCR. RESULTS: The number of correctly identified odors was significantly lower in COVID-19 than in controls (6 ± 3, vs. 10 ± 1 p = 0.028, r = 0.58). Total MoCA score was significantly lower in COVID-19 patients than in controls (20 ± 5 vs. 26 ± 3, p = 0.042, r = 0.54). Cognitive performance indicated by MoCA was associated with number of correctly identified odors in COVID-19 patients and controls (COVID-19: p = 0.018, 95% CI = 9-19; controls: p = 0.18, r = 0.63, 95% CI = 13-18.5 r = 0.64). DISCUSSION/CONCLUSION: OD is associated with cognitive impairment in controls and mild COVID-19. OD may represent a potentially useful clinical biomarker for subtle and even subclinical neurological involvement in severe acute respiratory distress syndrome coronavirus-2 infection.

[Automatic detection of epileptiform potentials and seizures in the EEG]. / Automatische Erkennung von epilepsietypischen Potenzialen und Anfällen im EEG.

Automatic computer-based algorithms for the detection of epileptiform potentials and seizure patterns on EEG facilitate a time-saving, objective method of quantitative EEG interpretation which is available 7/24. For the automatic detection of interictal epileptiform potentials sensitivities range from 65 to 99% with false positive detections of 0,09 to 13,4 per minute. Recent studies documented equal or even better performance of automatic spike detection programs compared with experienced human EEG readers. The seizure detection problem-one of the major problems in clinical epileptology-consists of the fact that the majority of focal onset seizures with impaired awareness and of seizures arising out of sleep occur unnoticed by patients and their caregivers. Automatic seizure detection systems could facilitate objective seizure documentation and thus help to solve the seizure detection problem. Furthermore, seizure detection systems may help to prevent seizure-related injuries and sudden unexpected death in epilepsy (SUDEP), and could be an integral part of novel, seizure-triggered on-demand therapies in epilepsy. During long-term video-EEG monitoring seizure detection systems could improve patient safety, provide a time-saving objective and reproducible analysis of seizure patterns and facilitate automatic computer-based patient testing during seizures. Sensitivities of seizure detection systems range from 75 to 90% with extratemporal seizures being more difficult to detect than temporal seizures. The false positive alarm rate ranges from 0,1 to 5 per 24 hours. Finally, machine learning algorithms, especially deep learning approaches, open a new highly promising era in automatic spike and seizure detection.

Transportable interrogation laser system with an instability of mod σy = 3 × 10-16.

We present an interrogation laser system for a transportable strontium lattice clock operating at 698 nm, which is based on an ultra-low-expansion glass reference cavity. Transportability is achieved by implementing a rigid, compact, and vibration insensitive mounting of the 12 cm-long reference cavity, sustaining shocks of up to 50 g. The cavity is mounted at optimized support points that independently constrain all degrees of freedom. This mounting concept is especially beneficial for cavities with a ratio of length L over diameter DL/D > 1. Generally, large L helps to reduce thermal noise-induced laser frequency instability while small D leads to small cavity volume. The frequency instability was evaluated, reaching its thermal noise floor of mod σy ≈ 3 × 10-16 for averaging times between 0.5 s and 10 s. The laser system was successfully operated during several field studies.

AChE-activity in critically ill patients with suspected septic encephalopathy: a prospective, single-centre study.

BACKGROUND: Up to 70% of septic patients develop a diffuse brain dysfunction named "septic associated encephalopathy" which is often solely based on clinical impressions. However, the diagnosis of septic associated encephalopathy is outcome-relevant due to an increase in mortality in these patients. Neuroinflammation as well as a disturbance of cholinergic transmission are assumed to be the causes of both delirium and septic associated encephalopathy. An alteration in cholinergic activity can be objectified by measuring the erythrocytic acetylcholinesterase-activity. Single-point measurements of acetylcholinesterase-activity are of limited value because individual and dynamic changes over time have to be anticipated. Therefore, the hypothesis should be tested whether a longitudinal analysis of acetylcholinesterase-activity in critically ill patients can help to diagnose a suspected septic-associated encephalopathy and whether acetylcholinesterase-activity differs in comparison to non-septic patients. METHODS: In this prospective, observational, single-center study, 175 patients (45 with sepsis, 130 without sepsis) were included. All patients were admitted to the surgical Intensive Care Unit of the University hospital Ulm, Germany. Patients were examined daily for the presence of delirium using the CAM-ICU. Daily measurement of the acetylcholinesterase-activity was performed in all patients. The possible time-dependent change in acetylcholinesterase-activity was analyzed with a linear regression model considering repeated measurements. Using a time-adjusted model further factors able to affect AChE-activity were investigated. For nonparametric distributions quantitative data were compared using Wilcoxon matched-pairs test. For analysis of independent samples the Mann-Whitney test was performed. RESULTS: About 90% of septic patients with suspected septic associated encephalopathy exhibited a statistically significant time-dependent in- or decrease in acetylcholinesterase-activity over a period of at least 5 consecutive days. CONCLUSION: Longitudinal measurement of acetylcholinesterase-activity over several consecutive days revealed a change from baseline only in septic patients with suspected septic-associated encephalopathy. Therefore, longitudinal measurement of acetylcholinesterase-activity is able to diagnose septic associated encephalopathy in septic patients with delirious symptoms. TRIAL REGISTRATION: Retrospectively registered at German Clinical Trials Register, registration number DRKS00020542 , date of registration: January 27, 2020.

[Sepsis Update: Definition and Epidemiology]. / Sepsis-Update: Definition und Epidemiologie.

Sepsis is a common disease in intensive care units worldwide, which is associated with relevant morbidity and mortality. Although massive research efforts have been made for decades, there is no specific therapy for sepsis to date. Decisive in the treatment of sepsis is the early diagnosis, because the outcome of the treated patients can be significantly improved by early elimination of the infection focus, the fastest possible administration of a broad, calculated antibiosis as well as the stabilization of the hemodynamic situation. A definition of the clinical picture of sepsis with high diagnostic sensitivity and specificity is therefore indispensable. This article describes the previously and the currently available definition of sepsis and gives an overview of the epidemiology of this disease.

Complement C5a Alters the Membrane Potential of Neutrophils during Hemorrhagic Shock.

BACKGROUND: Polymorphonuclear granulocytes (PMN) play a crucial role in host defense. Physiologically, exposure of PMN to the complement activation product C5a results in a protective response against pathogens, whereas in the case of systemic inflammation, excessive C5a substantially impairs neutrophil functions. To further elucidate the inability of PMN to properly respond to C5a, this study investigates the role of the cellular membrane potential of PMN in response to C5a. METHODS: Electrophysiological changes in cellular and mitochondrial membrane potential and intracellular pH of PMN from human healthy volunteers were determined by flow cytometry after exposure to C5a. Furthermore, PMN from male Bretoncelles-Meishan-Willebrand cross-bred pigs before and three hours after severe hemorrhagic shock were analyzed for their electrophysiological response. RESULTS: PMN showed a significant dose- and time-dependent depolarization in response to C5a with a strong response after one minute. The chemotactic peptide fMLP also evoked a significant shift in the membrane potential of PMN. Acidification of the cellular microenvironment significantly enhanced depolarization of PMN. In a clinically relevant model of porcine hemorrhagic shock, the C5a-induced changes in membrane potential of PMN were markedly diminished compared to healthy littermates. Overall, these membrane potential changes may contribute to PMN dysfunction in an inflammatory environment.

Effects of Hyperoxia and Mild Therapeutic Hypothermia During Resuscitation From Porcine Hemorrhagic Shock.

OBJECTIVE: Hemorrhagic shock-induced tissue hypoxia induces hyperinflammation, ultimately causing multiple organ failure. Hyperoxia and hypothermia can attenuate tissue hypoxia due to increased oxygen supply and decreased demand, respectively. Therefore, we tested the hypothesis whether mild therapeutic hypothermia and hyperoxia would attenuate postshock hyperinflammation and thereby organ dysfunction. DESIGN: Prospective, controlled, randomized study. SETTING: University animal research laboratory. SUBJECTS: Thirty-six Bretoncelles-Meishan-Willebrand pigs of either gender. INTERVENTIONS: After 4 hours of hemorrhagic shock (removal of 30% of the blood volume, subsequent titration of mean arterial pressure at 35 mm Hg), anesthetized and instrumented pigs were randomly assigned to "control" (standard resuscitation: retransfusion of shed blood, fluid resuscitation, norepinephrine titrated to maintain mean arterial pressure at preshock values, mechanical ventilation titrated to maintain arterial oxygen saturation > 90%), "hyperoxia" (standard resuscitation, but FIO2, 1.0), "hypothermia" (standard resuscitation, but core temperature 34°C), or "combi" (hyperoxia plus hypothermia) (n = 9 each). MEASUREMENTS AND MAIN RESULTS: Before, immediately at the end of and 12 and 22 hours after hemorrhagic shock, we measured hemodynamics, blood gases, acid-base status, metabolism, organ function, cytokine production, and coagulation. Postmortem kidney specimen were taken for histological evaluation, immunohistochemistry (nitrotyrosine, cystathionine γ-lyase, activated caspase-3, and extravascular albumin), and immunoblotting (nuclear factor-κB, hypoxia-inducible factor-1α, heme oxygenase-1, inducible nitric oxide synthase, B-cell lymphoma-extra large, and protein expression of the endogenous nuclear factor-κB inhibitor). Although hyperoxia alone attenuated the postshock hyperinflammation and thereby tended to improve visceral organ function, hypothermia and combi treatment had no beneficial effect. CONCLUSIONS: During resuscitation from near-lethal hemorrhagic shock, hyperoxia attenuated hyperinflammation, and thereby showed a favorable trend toward improved organ function. The lacking efficacy of hypothermia was most likely due to more pronounced barrier dysfunction with vascular leakage-induced circulatory failure.

A new 3D-printed overtube system for endoscopic submucosal dissection: first results of a randomized study in a porcine model.

BACKGROUND AND STUDY AIM: Endoscopic therapy of early malignant alterations can be difficult and cumbersome. Our research study group took advantage of new methods for rapid prototyping (i. e. 3D printing) to design and test an overtube system with two manipulator arms at the tip. Both arms can be steered independently from each other by a dedicated user platform. METHODS: This animal study involved a randomized evaluation of the new overtube device for endoscopic submucosal dissection (ESD) compared with a conventionally performed ESD. In total, 12 ESDs in six pigs were performed. Six ESDs were performed in the stomach and six in the colon. Size (in cm(2)) of resected specimens, the time needed to perform endoscopic resection, and adverse events were assessed. RESULTS: The overtube-assisted ESD was faster and therefore more effective than the conventional ESD technique (0.45 ±â€Š0.24 cm(2)/min vs. 0.22 ±â€Š0.11 cm(2)/min; P = 0.029). Only one adverse effect was recorded in the conventional group.  CONCLUSIONS: The overtube-assisted ESD was feasible in an animal model. ESD can be performed more quickly and potentially more effectively with the newly designed overtube device compared with the conventional ESD technique.

8 × 10⁻¹7 fractional laser frequency instability with a long room-temperature cavity.

We present a laser system based on a 48 cm long optical glass resonator. The large size requires a sophisticated thermal control and optimized mounting design. A self-balancing mounting was essential to reliably reach sensitivities to acceleration of below Δν/ν<2×10(-10)/g in all directions. Furthermore, fiber noise cancellations from a common reference point near the laser diode to the cavity mirror and to additional user points (Sr clock and frequency comb) are implemented. Through comparison with other cavity-stabilized lasers and with a strontium lattice clock, instability of below 1×10(-16) at averaging times from 1 to 1000 s is revealed.

Hyperglycemia, oxidative stress, and the diaphragm: a link between chronic co-morbidity and acute stress?

It is well established that prolonged, controlled mechanical ventilation is associated with contractile dysfunction of the diaphragm due to impaired function of the mitochondrial respiratory chain as a result of aggravated oxidative and nitrosative stress. Sepsis and circulatory failure induce a similar response pattern. Callahan and Supinski now show that streptozotocin-induced insulin-dependent diabetes causes a comparable response pattern, both with respect to function and physiology - that is, reduced fiber force and, consequently, muscle contractility - but also as far as the underlying mechanisms are concerned. In other words, the authors elegantly demonstrate that the consequences of a chronic metabolic disease and that of acute critical illness may lead to the same phenotype response. It remains to be elucidated whether the underlying co-morbidity (for example, diabetes) adds to or even synergistically enhances the effect of an acute stress situation (for example, sepsis, mechanical ventilation). In addition, extending their previous work during shock states, the authors also show that administration of a preparation of the enzymatic anti-oxidant superoxide dismutase can reverse the deleterious effects of diabetes. These data are discussed in the context of the fundamental role of hyperglycemia in relation to metabolism-dependent formation of reactive oxygen species.

Idiopathic generalized epilepsies in the epilepsy monitoring unit: Systematic quantification of focal EEG and semiological signs.

OBJECTIVE: Focal seizure symptoms (FSS) and focal interictal epileptiform discharges (IEDs) are common in patients with idiopathic generalized epilepsies (IGEs), but dedicated studies systematically quantifying them both are lacking. We used automatic IED detection and localization algorithms and correlated these EEG findings with clinical FSS for the first time in IGE patients. METHODS: 32 patients with IGEs undergoing long-term video EEG monitoring were systematically analyzed regarding focal vs. generalized IEDs using automatic IED detection and localization algorithms. Quantitative EEG findings were correlated with FSS. RESULTS: We observed FSS in 75% of patients, without significant differences between IGE subgroups. Mostly varying/shifting lateralizations of FSS across successive recorded seizures were seen. We detected a total of 81,949 IEDs, whereof 19,513 IEDs were focal (23.8%). Focal IEDs occurred in all patients (median 13% focal IEDs per patient, range 1.1 - 51.1%). Focal IED lateralization and localization predominance had no significant effect on FSS. CONCLUSIONS: All included patients with IGE showed focal IEDs and three-quarter had focal seizure symptoms irrespective of the specific IGE subgroup. Focal IED localization had no significant effect on lateralization and localization of FSS. SIGNIFICANCE: Our findings may facilitate diagnostic and treatment decisions in patients with suspected IGE and focal signs.

The obesity paradox and acute kidney injury: beneficial effects of hyper-inflammation?

In the general population, obesity is associated with an increased mortality risk, whereas several epidemiological studies demonstrated a protective effect of obesity in critically ill patients. In this context, Sleeman and colleagues investigated the effects of obesity on kidney function in a well-established porcine model of cardiopulmonary bypass. The authors confirm literature data that obesity per se is associated with a chronic hyper-inflammatory status. Nevertheless, obese swine undergoing the surgical procedure presented with attenuated kidney dysfunction and tissue apoptosis. The authors suggest that the chronic inflammation causes pre-conditioning against excessive acute hyper-inflammation. The authors have to be commended for using a long-term, clinically relevant model that, moreover, addresses a variety of putative mechanisms. The study is discussed in the context of the controversial findings that, in contrast to the existing literature on improved survival, most studies available suggest a higher incidence and severity of acute kidney injury in obese patients when compared with lean controls.

Hemorrhagic shock induces renal complement activation.

PURPOSE: Complement is activated in hemorrhagic shock and protective effects by specific complement inhibition were shown. However, it remains unclear if complement activation contributes to the local tissue damage and organ failure. Zonulin is known to activate complement and affect organ failure. Therefore, local and systemic complement activation during hemorrhagic shock and its consequences on zonulin were examined. METHODS: Porcine hemorrhagic shock (n = 9) was initiated with mean arterial blood pressure maintained constant for 4 h before retransfusion. Before, 4 h after hemorrhage and 12 and 22 h after resuscitation, central and renal blood samples were drawn. Analysis included HMGB-1, C3a, and zonulin (blood and kidney homogenisates) as well as terminal complement complex (TCC) and CH50 (blood). Organ samples were taken for histological and immunohistochemical analyses (C3c). RESULTS: HMGB-1 was significantly elevated in plasma 4 h after hemorrhagic shock and in homogenized kidneys. TCC after 12 h was significantly elevated centrally, while renal levels were not altered. In contrast, CH50 showed diminished renal values, while normal central levels were observed. Local complement activation was observed with enhanced C3c deposition in kidneys. Zonulin showed significantly diminished levels at 12 and 22 h after hemorrhagic shock (central and renal) and significantly correlated with levels of CH50 and neutrophil gelatinase-associated lipocalin (NGAL). CONCLUSION: The more pronounced complement activation centrally might indicate consumption of complement products in kidney tissue, which is underlined by C3c staining. Together with diminished levels of zonulin in both systemic and local samples, results could indicate the involvement of complement as well as zonulin in acute kidney failure.

Activation patterns of interictal epileptiform discharges in relation to sleep and seizures: An artificial intelligence driven data analysis.

OBJECTIVE: To quantify effects of sleep and seizures on the rate of interictal epileptiform discharges (IED) and to classify patients with epilepsy based on IED activation patterns. METHODS: We analyzed long-term EEGs from 76 patients with at least one recorded epileptic seizure during monitoring. IEDs were detected with an AI-based algorithm and validated by visual inspection. We then used unsupervised clustering to characterize patient sub-cohorts with similar IED activation patterns regarding circadian rhythms, deep sleep activation, and seizure occurrence. RESULTS: Five sub-cohorts with similar IED activation patterns were found: "Sporadic" (14%, n = 10) without or few IEDs, "Continuous" (32%, n = 23) with weak circadian/deep sleep or seizure modulation, "Nighttime & seizure activation" (23%, n = 17) with high IED rates during normal sleep times and after seizures but without deep sleep modulation, "Deep sleep" (19%, n = 14) with strong IED modulation during deep sleep, and "Seizure deactivation" (12%, n = 9) with deactivation of IEDs after seizures. Patients showing "Deep sleep" IED pattern were diagnosed with temporal lobe epilepsy in 86%, while 80% of the "Sporadic" cluster were extratemporal. CONCLUSIONS: Patients with epilepsy can be characterized by using temporal relationships between rates of IEDs, circadian rhythms, deep sleep and seizures. SIGNIFICANCE: This work presents the first approach to data-driven classification of epilepsy patients based on their fully validated temporal pattern of IEDs.

The Effects of Genetic 3-Mercaptopyruvate Sulfurtransferase Deficiency in Murine Traumatic-Hemorrhagic Shock.

INTRODUCTION: Hemorrhagic shock is a major cause of death after trauma. An additional blunt chest trauma independently contributes to mortality upon the development of an acute lung injury (ALI) by aggravating pathophysiological consequences of hemorrhagic shock. The maintenance of hydrogen sulfide availability is known to play an important role during hemorrhage and ALI. We therefore tested the impact of a genetic 3-mercaptopyruvate sulfurtransferase mutation (Δ3-MST) in a resuscitated murine model of traumatic-hemorrhagic shock. METHODS: Anesthetized wild-type (WT) and Δ3-MST mice underwent hemorrhagic shock with/without blunt chest trauma. Hemorrhagic shock was implemented for 1 h followed by retransfusion of shed blood and intensive care therapy for 4 h, including lung-protective mechanical ventilation, fluid resuscitation, and noradrenaline titrated to maintain a mean arterial pressure at least 50 mmHg. Systemic hemodynamics, metabolism, and acid-base status were assessed together with lung mechanics and gas exchange. Postmortem tissue samples were analyzed for immunohistological protein expression and mitochondrial oxygen consumption. RESULTS: 3-MST-deficient mice showed similar results in parameters of hemodynamics, gas exchange, metabolism, acid base status, and survival compared with the respective WT controls. Renal albumin extravasation was increased in Δ3-MST mice during hemorrhagic shock, together with a decrease of LEAK respiration in heart tissue. In contrast, mitochondrial oxygen consumption in the uncoupled state was increased in kidney and liver tissue of Δ3-MST mice subjected to the combined trauma. CONCLUSIONS: In summary, in a resuscitated murine model of traumatic-hemorrhagic shock, 3-MST deficiency had no physiologically relevant impact on hemodynamics and metabolism, which ultimately lead to unchanged mortality regardless of an additional blunt chest trauma.

Protective Effects of the Complement Inhibitor Compstatin CP40 in Hemorrhagic Shock.

Trauma-induced hemorrhagic shock (HS) plays a decisive role in the development of immune, coagulation, and organ dysfunction often resulting in a poor clinical outcome. Imbalanced complement activation is intricately associated with the molecular danger response and organ damage after HS. Thus, inhibition of the central complement component C3 as turnstile of both inflammation and coagulation is hypothesized as a rational strategy to improve the clinical course after HS.Applying intensive care conditions, anaesthetized, monitored, and protectively ventilated nonhuman primates (NHP; cynomolgus monkeys) received a pressure-controlled severe HS (60 min at mean arterial pressure 30 mmHg) with subsequent volume resuscitation. Thirty minutes after HS, animals were randomly treated with either an analog of the C3 inhibitor compstatin (i.e., Cp40) in saline (n = 4) or with saline alone (n = 4). The observation period lasted 300 min after induction of HS.We observed improved kidney function in compstatin Cp40-treated animals after HS as determined by improved urine output, reduced damage markers and a tendency of less histopathological signs of acute kidney injury. Sham-treated animals revealed classical signs of mucosal edema, especially in the ileum and colon reflected by worsened microscopic intestinal injury scores. In contrast, Cp40-treated HS animals exhibited only minor signs of organ edema and significantly less intestinal damage. Furthermore, early systemic inflammation and coagulation dysfunction were both ameliorated by Cp40.The data suggest that therapeutic inhibition of C3 is capable to significantly improve immune, coagulation, and organ function and to preserve organ-barrier integrity early after traumatic HS. C3-targeted complement inhibition may therefore reflect a promising therapeutic strategy in fighting fatal consequences of HS.