A novel approach for in vivo DNA footprinting using short double-stranded cell-free DNA from plasma.

Here, we present a method for enrichment of double-stranded cfDNA with an average length of ∼40 bp from cfDNA for high-throughput DNA sequencing. This class of cfDNA is enriched at gene promoters and binding sites of transcription factors or structural DNA-binding proteins, so that a genome-wide DNA footprint is directly captured from liquid biopsies. In short double-stranded cfDNA from healthy individuals, we find significant enrichment of 203 transcription factor motifs. Additionally, short double-stranded cfDNA signals at specific genomic regions correlate negatively with DNA methylation, positively with H3K4me3 histone modifications and gene transcription. The diagnostic potential of short double-stranded cell-free DNA (cfDNA) in blood plasma has not yet been recognized. When comparing short double-stranded cfDNA from patient samples of pancreatic ductal adenocarcinoma with colorectal carcinoma or septic with postoperative controls, we identify 136 and 241 differentially enriched loci, respectively. Using these differentially enriched loci, the disease types can be clearly distinguished by principal component analysis, demonstrating the diagnostic potential of short double-stranded cfDNA signals as a new class of biomarkers for liquid biopsies.

Prevalence of relevant early complications during the first 24 h on a normal ward in patients following PACU care after medium and major surgery: a monocentric retrospective observational study.

PURPOSE: Even today, it remains a challenge for healthcare professionals to decide whether a clinically stable patient who is recovering from uncomplicated medium or major surgery would benefit from a postoperative intensive care unit (ICU) admission, or whether they would be at least as adequately cared for by a few hours of monitoring in the post-operative care unit (PACU). METHODS: In this monocentric retrospective observational study, all adult patients who (Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin (DGAI) in Anästh Intensivmed (50):S486-S489, 2009) underwent medium or major surgery between 1 January 1 2014 and 31 December 2018 at the Heidelberg University Surgical Center, and (Vimlati et al. in Eur J Anaesthesiol September 26(9):715-721, 2009) were monitored for 1-12 h in the PACU, and then (De Pietri et al. in World J Gastroenterol 20(9):2304-23207, 2014) transferred to a normal ward (NW) immediately thereafter were included. At the end of the PACU stay, each patient was cleared by both a surgeon and an anesthesiologist to be transferred to a NW. The first objective of this study was to determine the prevalence of relevant early complications (RECs) within the first 24 h on a normal ward. The secondary objective was to determine the prevalence of RECs in the subgroup of included patients who underwent partial pancreaticoduodenectomy. RESULTS: A total of 10,273 patients were included in this study. The prevalence of RECs was 0.50% (confidence interval [CI] 0.40-0.60%), with the median length of stay in the PACU before the patient's first transfer to a NW being 285 min (interquartile range 210-360 min). In the subgroup of patients who underwent partial pancreaticoduodenectomy (n = 740), REC prevalence was 1.1% (CI = 0.55-2.12%). CONCLUSION: Based on a medical case-by-case assessment, it is possible to select patients who after a PACU stay of only up to 12 h have a low risk of emergency readmission to an ICU within the 24 h following the transfer to the NW. Continued research will be needed to further improve transfer decisions in such low-risk subgroups.

Establishing Medical Intelligence - Leveraging FHIR to Improve Clinical Management: a retrospective cohort and clinical implementation study.

BACKGROUND: FHIR (Fast Healthcare Interoperability Resources) has been proposed to enable health data interoperability. So far, its applicability has been demonstrated for selected research projects with limited data. OBJECTIVE: Here, we designed and implemented a conceptual medical intelligence framework to leverage real-world care data for clinical decision-making. METHODS: A Python package for the utilization of multimodal FHIR data (FHIRPACK) was developed and pioneered in five real-world clinical use cases, i.e., myocardial infarction (MI), stroke, diabetes, sepsis, and prostate cancer (PC). Patients were identified based on ICD-10 codes, and outcomes were derived from laboratory tests, prescriptions, procedures, and diagnostic reports. Results were provided as browser-based dashboards. RESULTS: For 2022, 1,302,988 patient encounters were analyzed. MI: In 72.7% of cases (N=261) medication regimens fulfilled guideline recommendations. Stroke: Out of 1,277 patients, 165 patients received thrombolysis and 108 thrombectomy. Diabetes: In 443,866 serum glucose and 16,180 HbA1c measurements from 35,494 unique patients, the prevalence of dysglycemic findings was 39% (N=13,887). Among those with dysglycemia, diagnosis was coded in 44.2% (N=6,138) of the patients. Sepsis: In 1,803 patients, Staphylococcus epidermidis was the primarily isolated pathogen (N=773, 28.9%) and piperacillin/tazobactam was the primarily prescribed antibiotic (N=593, 37.2%). PC: Three out of 54 patients who received radical prostatectomy were identified as cases with PSA persistence or biochemical recurrence. CONCLUSIONS: Leveraging FHIR data through large-scale analytics can enhance healthcare quality and improve patient outcomes across five clinical specialties. We identified i) sepsis patients requiring less broad antibiotic therapy, ii) patients with myocardial infarction who could benefit from statin and antiplatelet therapy, iii) stroke patients with longer than recommended times to intervention, iv) patients with hyperglycemia who could benefit from specialist referral and v) PC patients with early increases in cancer markers.

Preoperative Anxiolysis and Treatment Expectation (PATE Trial): open-label placebo treatment to reduce preoperative anxiety in female patients undergoing gynecological laparoscopic surgery - study protocol for a bicentric, prospective, randomized-controlled trial.

One of the most common concerns of patients undergoing surgery is preoperative anxiety, with a prevalence of up to 48%. The effects of preoperative anxiety continue beyond the preoperative period and are associated with more severe postoperative pain and poorer treatment outcomes. Treatment options for preoperative anxiety are often limited as sedatives cause side effects and their efficacy remains controversial. Placebo research has shown that optimization of positive treatment expectations, as can be achieved through placebo administration and education, has clinically relevant effects on preoperative anxiety, pain and treatment outcomes. As the administration of masked placebos raises ethical questions, clinical studies have increasingly focused on the use of open, non-deceptive placebo administration (open-label placebo, OLP). The use of OLPs to reduce preoperative anxiety and modify clinically relevant postoperative outcomes has not yet been investigated. This bicentric, prospective, randomized-controlled clinical trial (PATE Trial; German Registry for Clinical Studies DRKS00033221), an associated project of the Collaborative Research Center (CRC) 289 "Treatment Expectation", aims to alleviate preoperative anxiety by optimizing positive treatment expectations facilitated by OLP. Furthermore, this study examines a potential enhancement of these effects through aspects of observational learning, operationalized by a positive expectation-enhancing video. In addition, patient's perspective on the self-efficacy and appropriateness of OLPs prior to surgery will be assessed. To achieve these objectives, female patients will be randomized into three groups before undergoing gynecological laparoscopic surgery. One group receives the OLP with a positive rationale conveyed by a study physician. A second group receives the same intervention, OLP administration and rationale provided by a physician, and additionally watches a video on OLP presenting a satisfied patient. A third group receives standard treatment as usual (TAU). Outcome measures will be effects on preoperative anxiety and postoperative experience, particularly visceral and somatic postoperative pain. As the non-deceptive administration of placebos; when indicated; may yield positive outcomes without side effects, and as current treatment of preoperative anxiety is limited, evidence from clinical placebo research has the potential to improve outcomes and patient experience in the surgical setting.

A proof of concept for microcirculation monitoring using machine learning based hyperspectral imaging in critically ill patients: a monocentric observational study.

BACKGROUND: Impaired microcirculation is a cornerstone of sepsis development and leads to reduced tissue oxygenation, influenced by fluid and catecholamine administration during treatment. Hyperspectral imaging (HSI) is a non-invasive bedside technology for visualizing physicochemical tissue characteristics. Machine learning (ML) for skin HSI might offer an automated approach for bedside microcirculation assessment, providing an individualized tissue fingerprint of critically ill patients in intensive care. The study aimed to determine if machine learning could be utilized to automatically identify regions of interest (ROIs) in the hand, thereby distinguishing between healthy individuals and critically ill patients with sepsis using HSI. METHODS: HSI raw data from 75 critically ill sepsis patients and from 30 healthy controls were recorded using TIVITA® Tissue System and analyzed using an automated ML approach. Additionally, patients were divided into two groups based on their SOFA scores for further subanalysis: less severely ill (SOFA ≤ 5) and severely ill (SOFA > 5). The analysis of the HSI raw data was fully-automated using MediaPipe for ROI detection (palm and fingertips) and feature extraction. HSI Features were statistically analyzed to highlight relevant wavelength combinations using Mann-Whitney-U test and Benjamini, Krieger, and Yekutieli (BKY) correction. In addition, Random Forest models were trained using bootstrapping, and feature importances were determined to gain insights regarding the wavelength importance for a model decision. RESULTS: An automated pipeline for generating ROIs and HSI feature extraction was successfully established. HSI raw data analysis accurately distinguished healthy controls from sepsis patients. Wavelengths at the fingertips differed in the ranges of 575-695 nm and 840-1000 nm. For the palm, significant differences were observed in the range of 925-1000 nm. Feature importance plots indicated relevant information in the same wavelength ranges. Combining palm and fingertip analysis provided the highest reliability, with an AUC of 0.92 to distinguish between sepsis patients and healthy controls. CONCLUSION: Based on this proof of concept, the integration of automated and standardized ROIs along with automated skin HSI analyzes, was able to differentiate between healthy individuals and patients with sepsis. This approach offers a reliable and objective assessment of skin microcirculation, facilitating the rapid identification of critically ill patients.

Echocardiographic right ventricular evaluation in cardiac surgery patients undergoing mitral valve reconstruction: a single center prospective observational study.

Background: Mitral valve (MV) regurgitation (MR) is the second most frequent indication for valvular surgery in Europe. Right ventricular (RV) dysfunction is a common finding after cardiac surgery and might persist for years. The RV-function after MV surgery has been controversially discussed. We therefore aimed to evaluate early RV-performance in patients undergoing MV surgery. Methods: Between 09/2020 and 06/2022, ninety-two patients presenting with MR undergoing MV surgery were consented and prospectively included for evaluation. Echocardiographic evaluation was performed one day before surgery, one week after surgery and three months later. Primary endpoints reported RV-function changes including tricuspid annular plane systolic excursion (TAPSE), RV systolic prime (S') and fractional area change (FAC). Secondary endpoints included stability of MV repair, changes in left ventricular functions and early mortality. Results: Mean patients' age was 59.1±11.4 years. Fifty-five (59.7%) patients were male. Most of patients presented with severe (n=88; 95.7%) MR. Mean systolic pulmonary artery pressure was 35.6±15.7 mmHg. Moderate or severe pulmonary arterial hypertension (PAH) was present in 60 (65.2%) patients. Patients underwent either isolated MV surgery (n=67; 72.8%) or combined with tricuspid valve surgery (n=25; 27.2%). Minimal invasive surgery was performed in 26.1% (n=24) of the patients. Postoperative short-term follow-up at 3 months reported RV-dysfunction in 44.5% (n=41) of the patients as indicated by reductions in TAPSE & RV S' from 21.2±4.7 to 14±3.3 mm (P<0.001) and from 14.7±4.3 to 9.7±2.8 cm/s (P<0.001) respectively. The FAC reduction from 42.9%±9.6% to 42.2%±9.9% was non-significant (P=0.593) and no need for redo mitral or tricuspid valve surgery was reported. Finally, the presence and severity of preoperative PAH played significant roles for the incidence of RV dysfunction, P=0.021 and P=0.047, respectively. Minimal invasive surgical procedure significantly reduced the incidence of postoperative RV-dysfunction (P=0.013). Conclusions: Study early results report a significant reduction of RV-function after MV surgery as measured by TAPSE, & RV S', even when the FAC remains unchanged. Even though, this finding has limited prognostic implications during an uneventful surgical course.

Suppression PCR-Based Selective Enrichment Sequencing for Pathogen and Antimicrobial Resistance Detection on Cell-Free DNA in Sepsis-A Targeted, Blood Culture-Independent Approach for Rapid Pathogen and Resistance Diagnostics in Septic Patients.

Sepsis is a life-threatening syndrome triggered by infection and accompanied by high mortality, with antimicrobial resistances (AMRs) further escalating clinical challenges. The rapid and reliable detection of causative pathogens and AMRs are key factors for fast and appropriate treatment, in order to improve outcomes in septic patients. However, current sepsis diagnostics based on blood culture is limited by low sensitivity and specificity while current molecular approaches fail to enter clinical routine. Therefore, we developed a suppression PCR-based selective enrichment sequencing approach (SUPSETS), providing a molecular method combining multiplex suppression PCR with Nanopore sequencing to identify most common sepsis-causative pathogens and AMRs using plasma cell-free DNA. Applying only 1 mL of plasma, we targeted eight pathogens across three kingdoms and ten AMRs in a proof-of-concept study. SUPSETS was successfully tested in an experimental research study on the first ten clinical samples and revealed comparable results to clinical metagenomics while clearly outperforming blood culture. Several clinically relevant AMRs could be additionally detected. Furthermore, SUPSETS provided first pathogen and AMR-specific sequencing reads within minutes of starting sequencing, thereby potentially decreasing time-to-results to 11-13 h and suggesting diagnostic potential in sepsis.

[Position paper on working in the intensive care unit during pregnancy : DIVI recommendations for improving the situation of pregnant employees in the ICU]. / Positionspapier zum Arbeiten in der Schwangerschaft auf der Intensivstation : DIVI-Empfehlungen zur Verbesserung der Lage von schwangeren Mitarbeiterinnen auf einer Intensivstation.

The Maternity Protection Act is intended to protect the mother and the child from hazards, excessive demands and damage to health in the workplace, and from financial disadvantages and loss of employment. However, the objectives defined by the Maternity Protection Act-the safety and health of the pregnant employee on the one hand and the prevention of disadvantages in working life on the other-are not yet adequately achieved in the intensive care unit (ICU). Implementation of the Maternity Protection Act to the benefit of all involved parties should also be promoted in the specialist areas represented by the DIVI, in particular the work of pregnant physicians and nursing staff and other working specialists (respiratory therapists, physiotherapists, speech therapists, psychotherapists, and social workers) in the ICU. The aim of this paper is to raise awareness of the need to consider each pregnant and breastfeeding staff member individually and to work together to find a personal solution for continuing to work in the ICU. Possible ways and solutions to achieve this goal are outlined and practical examples are given for implementation in everyday clinical routine. These are also based on comprehensive presentation of activities according to a traffic light color-code system for all occupational groups. Arguments against pregnant employees working in the ICU are discussed and possible solutions are presented.

[Position paper on working in the intensive care unit during pregnancy : DIVI recommendations for improving the situation of pregnant employees in the ICU]. / Positionspapier zum Arbeiten in der Schwangerschaft auf der Intensivstation : DIVI-Empfehlungen zur Verbesserung der Lage von schwangeren Mitarbeiterinnen auf einer Intensivstation.

The Maternity Protection Act is intended to protect the mother and the child from hazards, excessive demands and damage to health in the workplace, and from financial disadvantages and loss of employment. However, the objectives defined by the Maternity Protection Act-the safety and health of the pregnant employee on the one hand and the prevention of disadvantages in working life on the other-are not yet adequately achieved in the intensive care unit (ICU). Implementation of the Maternity Protection Act to the benefit of all involved parties should also be promoted in the specialist areas represented by the DIVI, in particular the work of pregnant physicians and nursing staff and other working specialists (respiratory therapists, physiotherapists, speech therapists, psychotherapists, and social workers) in the ICU. The aim of this paper is to raise awareness of the need to consider each pregnant and breastfeeding staff member individually and to work together to find a personal solution for continuing to work in the ICU. Possible ways and solutions to achieve this goal are outlined and practical examples are given for implementation in everyday clinical routine. These are also based on comprehensive presentation of activities according to a traffic light color-code system for all occupational groups. Arguments against pregnant employees working in the ICU are discussed and possible solutions are presented.

Triggering receptor expressed on myeloid cells-1 in sepsis, and current insights into clinical studies.

Triggering receptor expressed on myeloid cells-1 (TREM-1) is a pattern recognition receptor and plays a critical role in the immune response. TREM-1 activation leads to the production and release of proinflammatory cytokines, chemokines, as well as its own expression and circulating levels of the cleaved soluble extracellular portion of TREM-1 (sTREM-1). Because patients with sepsis and septic shock show elevated sTREM-1 levels, TREM-1 has attracted attention as an important contributor to the inadequate immune response in this often-deadly condition. Since 2001, when the first blockade of TREM-1 in sepsis was performed, many potential TREM-1 inhibitors have been established in animal models. However, only one of them, nangibotide, has entered clinical trials, which have yielded promising data for future treatment of sepsis, septic shock, and other inflammatory disease such as COVID-19. This review discusses the TREM-1 pathway and important ligands, and highlights the development of novel inhibitors as well as their clinical potential for targeted treatment of various inflammatory conditions.

[Guideline-conform treatment of sepsis]. / Leitliniengerechte Therapie der Sepsis.

The time to administration of broad-spectrum antibiotics and (secondarily) to the initiation of hemodynamic stabilization are the most important factors influencing survival of patients with sepsis and septic shock; however, the basic prerequisite for the initiation of an adequate treatment is that a suspected diagnosis of sepsis is made first. Therefore, the treatment of sepsis, even before it has begun, is an interdisciplinary and interprofessional task. This article provides an overview of the current state of the art in sepsis treatment and points towards new evidence that has the potential to change guideline recommendations in the coming years. In summary, the following points are critical: (1) sepsis must be diagnosed as soon as possible and the implementation of a source control intervention (in case of a controllable source) has to be implemented as soon as (logistically) possible. (2) In general, intravenous broad-spectrum antibiotics should be given within the first hour after diagnosis if sepsis or septic shock is suspected. In organ dysfunction without shock, where sepsis is a possible but unlikely cause, the results of focused advanced diagnostics should be awaited before a decision to give broad-spectrum antibiotics is made. If it is not clear within 3 h whether sepsis is the cause, broad-spectrum antibiotics should be given when in doubt. Administer beta-lactam antibiotics as a prolonged (or if therapeutic drug monitoring is available, continuous) infusion after an initial loading dose. (3) Combination treatment with two agents for one pathogen group should remain the exception (e.g. multidrug-resistant gram-negative pathogens). (4) In the case of doubt, the duration of anti-infective treatment should rather be shorter than longer. Procalcitonin can support the clinical decision to stop (not to start!) antibiotic treatment! (5) For fluid treatment, if hypoperfusion is present, the first (approximately) 2L (30 ml/kg BW) of crystalloid solution is usually safe and indicated. After that, the rule is: less is more! Any further fluid administration should be carefully weighed up with the help of dynamic parameters, the patient's clinical condition and echo(cardio)graphy.

Extracellular Vesicles as Possible Plasma Markers and Mediators in Patients with Sepsis-Associated Delirium-A Pilot Study.

Patients with sepsis-associated delirium (SAD) show severe neurological impairment, often require an intensive care unit (ICU) stay and have a high risk of mortality. Hence, useful biomarkers for early detection of SAD are urgently needed. Extracellular vesicles (EVs) and their cargo are known to maintain normal physiology but also have been linked to numerous disease states. Here, we sought to identify differentially expressed proteins in plasma EVs from SAD patients as potential biomarkers for SAD. Plasma EVs from 11 SAD patients and 11 age-matched septic patients without delirium (non-SAD) were isolated by differential centrifugation, characterized by nanoparticle tracking analysis, transmission electron microscopy and Western blot analysis. Differential EV protein expression was determined by mass spectrometry and the resulting proteomes were characterized by Gene Ontology term and between-group statistics. As preliminary results because of the small group size, five distinct proteins showed significantly different expression pattern between SAD and non-SAD patients (p ≤ 0.05). In SAD patients, upregulated proteins included paraoxonase-1 (PON1), thrombospondin 1 (THBS1), and full fibrinogen gamma chain (FGG), whereas downregulated proteins comprised immunoglobulin (IgHV3) and complement subcomponent (C1QC). Thus, plasma EVs of SAD patients show significant changes in the expression of distinct proteins involved in immune system regulation and blood coagulation as well as in lipid metabolism in this pilot study. They might be a potential indicator for to the pathogenesis of SAD and thus warrant further examination as potential biomarkers, but further research is needed to expand on these findings in longitudinal study designs with larger samples and comprehensive polymodal data collection.

Serum KL-6 as a Candidate Predictor of Outcome in Patients with SARS-CoV-2 Pneumonia.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-infection is associated with an extremely variable disease course. When interstitial pneumonia (IP) occurs, it can lead to acute respiratory distress syndrome and death. Serum Krebs von den Lungen-6 (KL-6) is an established marker of IP, but its role as a marker of SARS-CoV-2 pneumonia is debated. This bicentric study included 157 patients with SARS-CoV-2 pneumonia. The WHO Ordinal Scale for Clinical Improvement (0-10 points) was used to classify the clinical course. Serum samples were collected at admission, and on days 3 and 7 of hospitalization. KL-6 was measured by using automated chemiluminescence immunoassay. A total of 68 patients developed a severe SARS-CoV-2 pneumonia, 135 of them required oxygen, and 15 died during hospitalization. The patients requiring non-invasive ventilation, invasive ventilation, or extracorporeal membrane oxygenation had significantly higher serum KL-6 levels at admission. The serum KL-6 levels were tendentially higher in patients who died than in those who survived. Logistic regression identified serum KL-6 at a cut-off of 335 U/mL at admission as a significant predictor of severe SARS-CoV-2 pneumonia outcome. Serum KL-6 seems to be a candidate biomarker for the clinical routine to stratify patients with SARS-CoV-2 pneumonia for the risk of a severe disease outcome or death.

Macrophage migration inhibitory factor receptor CD74 expression is associated with expansion and differentiation of effector T cells in COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused millions of COVID-19 cases and deaths worldwide. Severity of pulmonary pathologies and poor prognosis were reported to be associated with the activation non-virus-specific bystander T cells. In addition, high concentrations of the macrophage migration inhibitory factor (MIF) were found in serum of COVID-19 patients. We hypothesized that these two pathogenic factors might be related and analyzed the expression of receptors for MIF on T cells in COVID-19. T cells from PBMCs of hospitalized patients with mild and severe COVID-19 were characterized. A significantly higher proportion of CD4+ and CD8+ T cells from COVID-19 patients expressed CD74 on the cell surface compared to healthy controls. To induce intracellular signaling upon MIF binding, CD74 forms complexes with CD44, CXCR2, or CXCR4. The vast majority of CD74+ T cells expressed CD44, whereas expression of CXCR2 and CXCR4 was low in controls but increased upon SARS-CoV-2 infection. Hence, T cells in COVID-19 patients express receptors that render them responsive to MIF. A detailed analysis of CD74+ T cell populations revealed that most of them had a central memory phenotype early in infection, while cells with an effector and effector memory phenotype arose later during infection. Furthermore, CD74+ T cells produced more cytotoxic molecules and proliferation markers. Our data provide new insights into the MIF receptor and co-receptor repertoire of bystander T cells in COVID-19 and uncovers a novel and potentially druggable aspect of the immunological footprint of SARS-CoV-2.

Bedside Hyperspectral Imaging and Organ Dysfunction Severity in Critically Ill COVID-19 Patients-A Prospective, Monocentric Observational Study.

Hyperspectral imaging (HSI) is a non-invasive technology that provides information on biochemical tissue properties, including skin oxygenation and perfusion quality. Microcirculatory alterations are associated with organ dysfunction in septic COVID-19 patients. This prospective observational study investigated associations between skin HSI and organ dysfunction severity in critically ill COVID-19 patients. During the first seven days in the ICU, palmar HSI measurements were carried out with the TIVITA® tissue system. We report data from 52 critically ill COVID-19 patients, of whom 40 required extracorporeal membrane oxygenation (ECMO). HSI parameters for superficial tissue oxygenation (StO2) and oxygenation and perfusion quality (NPI) were persistently decreased. Hemoglobin tissue content (THI) increased, and tissue water content (TWI) was persistently elevated. Regression analysis showed strong indications for an association of NPI and weaker indications for associations of StO2, THI, and TWI with sequential organ failure assessment (SOFA) scoring. StO2 and NPI demonstrated negative associations with vasopressor support and lactate levels as well as positive associations with arterial oxygen saturation. These results suggest that skin HSI provides clinically relevant information, opening new perspectives for microcirculatory monitoring in critical care.

Non-Neuronal Acetylcholinesterase Activity Shows Limited Utility for Early Detection of Sepsis.

(1) Background: Sepsis is a severe systemic inflammatory condition characterized by rapid clinical deterioration and organ dysfunction. The cholinergic system has been implicated in modulating the inflammatory response. Acetylcholinesterase (AChE), an enzyme primarily responsible for the hydrolysis of acetylcholine, has been proposed as a potential early indicator of sepsis onset. However, the exact role of non-neuronal AChE activity in sepsis and its correlation with disease severity and patient outcomes remain unclear. This study aimed to investigate the involvement of AChE activity in sepsis and evaluate its association with disease severity and clinical outcomes. (2) Methods: A prospective study included 43 septic patients. AChE activity was measured at sepsis detection, as well as 7 and 28 days later. Inflammatory biomarkers, disease severity scores, and patient outcomes were evaluated. (3) Results: AChE activity remained stable for 7 days and decreased at 28 days. However, there was no correlation between initial AChE activity and inflammatory biomarkers, disease severity scores, ICU stay, or hospital stay. (4) Conclusions: Non-neuronal AChE activity may not reliably indicate early sepsis or predict disease severity.

Recommendations on the structure, personal, and organization of intensive care units.

Background: Intensive care units (ICU) are central facilities of medical care in hospitals world-wide and pose a significant financial burden on the health care system. Objectives: To provide guidance and recommendations for the requirements of (infra)structure, personal, and organization of intensive care units. Design and setting: Development of recommendations based on a systematic literature search and a formal consensus process from a group of multidisciplinary and multiprofessional specialists from the German Interdisciplinary Association of Intensive Care and Emergency Medicine (DIVI). The grading of the recommendation follows the report from an American College of Chest Physicians Task Force. Results: The recommendations cover the fields of a 3-staged level of intensive care units, a 3-staged level of care with respect to severity of illness, qualitative and quantitative requirements of physicians and nurses as well as staffing with physiotherapists, pharmacists, psychologists, palliative medicine and other specialists, all adapted to the 3 levels of ICUs. Furthermore, proposals concerning the equipment and the construction of ICUs are supplied. Conclusion: This document provides a detailed framework for organizing and planning the operation and construction/renovation of ICUs.