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Integrity of epithelial and endothelial cell barriers is of critical importance for health, barrier disruption is a hallmark of numerous diseases, of which many are driven by carbonyl stressors such as methylglyoxal (MG). Carnosine and anserine exert some MG-quenching activity, but the impact of these and of other histidine containing dipeptides on cell barrier integrity has not been explored in detail. In human proximal tubular (HK-2) and umbilical vein endothelial (HUVEC) cells, exposure to 200 µM MG decreased transepithelial resistance (TER), i.e. increased ionic permeability and permeability for 4-, 10- and 70-kDa dextran, membrane zonula occludens (ZO-1) abundance was reduced, methylglyoxal 5-hydro-5-methylimidazolones (MG-H1) formation was increased. Carnosine, balenine (ß-ala-1methyl-histidine) and anserine (ß-ala-3-methyl-histidine) ameliorated MG-induced reduction of TER in both cell types. Incubation with histidine, 1-/3-methylhistidine, but not with ß-alanine alone, restored TER, although to a lower extent than the corresponding dipeptides. Carnosine and anserine normalized transport and membrane ZO-1 abundance. Aminoguanidine, a well-described MG-quencher, did not mitigate MG-induced loss of TER. Our results show that the effects of the dipeptides on epithelial and endothelial resistance and junction function depend on the methylation status of histidine and are not exclusively explained by their quenching activity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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Copyright of Medizinische Klinik: Intensivmedizin & Notfallmedizin is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

It has recently been shown that von Willebrand factor (VWF) multimers contribute to immunothrombosis in Coronavirus disease 2019 (COVID-19). Since COVID-19 is associated with an increased risk of autoreactivity, the present study investigates, whether the generation of autoantibodies to ADAMTS13 contributes to this finding. In this observational prospective controlled multicenter study blood samples and clinical data of patients hospitalized for COVID-19 were collected from April to November 2020. The study included 156 individuals with 90 patients having confirmed COVID-19 of mild to critical severity. 30 healthy individuals and 36 critically ill ICU patients without COVID-19 served as controls. ADAMTS13 antibodies occurred in 31 (34.4%) COVID-19 patients. Antibodies occurred more often in critically ill COVID-19 patients (55.9%) than non-COVID-19 ICU patients and healthy controls (5.6% and 6.7%; p < 0.001), respectively. Generation of ADAMTS13 antibodies in COVID-19 was associated with lower ADAMTS13 activity (56.5%, interquartile range (IQR) 21.25 vs. 71.5%, IQR 24.25, p = 0.0041), increased disease severity (severe or critical in 90% vs. 62.3%, p = 0.019), and a trend to higher mortality (35.5% vs. 18.6%, p = 0.077). Median time to antibody development was 11 days after first positive SARS-CoV-2-PCR specimen. Gel analysis of VWF multimers resembled the constellation in patients with TTP. The present study demonstrates for the first time, that generation of ADAMTS13 antibodies is frequent in COVID-19, associated with lower ADAMTS13 activity and increased risk of an adverse disease course. These findings provide a rationale to include ADAMTS13 antibodies in the diagnostic workup of SARS-CoV-2 infections. [ABSTRACT FROM AUTHOR]

In order to identify biomarkers for earlier prediction of COVID-19 outcome, we collected blood samples from patients with fatal outcomes (non-survivors) and with positive clinical outcomes (survivors) at ICU admission and after seven days. COVID-19 survivors and non-survivors showed significantly different transcript levels for 93 genes in whole blood already at ICU admission as revealed by RNA-Seq. These differences became even more pronounced at day 7, resulting in 290 differentially expressed genes. Many identified genes play a role in the differentiation of hematopoietic cells. For validation, we designed an RT-qPCR assay for C-type lectin domain family 12 member A (CLEC12A) and acetylcholinesterase (ACHE), two transcripts that showed highest potential to discriminate between survivors and non-survivors at both time points. Using our combined RT-qPCR assay we examined 33 samples to accurately predict patient survival with an AUROC curve of 0.931 (95% CI = 0.814–1.000) already at ICU admission. CLEC12A and ACHE showed improved prediction of patient outcomes compared to standard clinical biomarkers including CRP and PCT in combination (AUROC = 0.403, 95% CI = 0.108–0.697) or SOFA score (AUROC = 0.701 95% CI = 0.451–0.951) at day 0. Therefore, analyzing CLEC12A and ACHE gene expression from blood may provide a promising approach for early risk stratification of severely ill COVID-19 patients. [ABSTRACT FROM AUTHOR]

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Background: Sepsis and septic shock are frequently accompanied by coagulopathy. Since the sepsis-induced coagulopathy (SIC) score was first described, subsequent studies from Asia revealed a SIC prevalence of 40–60%. In Europe, however, SIC prevalence in patients fulfilling sepsis criteria according to the third international consensus definition (SEPSIS-3) has not yet been evaluated. Methods: The Critical Care Trials Group of the German Sepsis Competence Network (SepNet) conducted a secondary analysis of two randomized controlled trials. Only patients fulfilling sepsis criteria according SEPSIS-3 were included in this secondary analysis. In a two step approach, SIC prevalence was determined in 267 patients with sepsis but not septic shock (at the time of inclusion) from the “Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis” (HYPRESS) trial. Then, we estimated SIC prevalence in 1,018 patients from the “Effect of Sodium Selenite Administration and Procalcitonin-Guided Therapy on Mortality in Patients With Severe Sepsis or Septic Shock” (SISPCT) trial using a simplified SIC score based on the platelet-SIC-subscore (PSSC). Study aims were to assess (i) the prevalence of SIC in patients with SEPSIS-3, (ii) the association of SIC with 90-day mortality and morbidity, (iii) the time when patients become SIC positive during the course of sepsis, and (iv) the value of the PSSC for predicting SIC. Results: In the HYPRESS trial, SIC prevalence was 22.1% (95% confidence interval [CI] 17.5–27.5%). The estimated SIC prevalence in the SISPCT trial was 24.2% (95% CI 21.6–26.9%). In the HYPRESS trial, SIC was associated with significantly higher 90-day mortality (13.9% vs. 26.8%, p = 0.027) and morbidity. Logistic regression analysis adjusted for age, sex, treatment arm, and (SIC-adapted) SOFA score confirmed the negative association of SIC with survival (p = 0.011). In the SISPCT trial, increased PSSCs were associated with higher 90-day mortality (PSSC 0: 34.4%, PSSC 1: 40.5%, PSSC 2: 53.3%; p < 0.001). In both trials, SIC was already present at sepsis diagnosis or occurred during the following 4 days. Conclusions: SIC is a clinically relevant complication of sepsis. Although it might be less frequent than previously reported, its occurrence is associated with higher morbidity and mortality and should be interpreted as an early warning sign. [ABSTRACT FROM AUTHOR]

The complex process of manual biomarker extraction from body composition analysis (BCA) has far restricted the analysis of SARS-CoV-2 outcomes to small patient cohorts and a limited number of tissue types. We investigate the association of two BCA-based biomarkers with the development of severe SARS-CoV-2 infections for 918 patients (354 female, 564 male) regarding disease severity and mortality (186 deceased). Multiple tissues, such as muscle, bone, or adipose tissue are used and acquired with a deep-learning-based, fully-automated BCA from computed tomography images of the chest. The BCA features and markers were univariately analyzed with a Shapiro–Wilk and two-sided Mann–Whitney-U test. In a multivariate approach, obtained markers were adjusted by a defined set of laboratory parameters promoted by other studies. Subsequently, the relationship between the markers and two endpoints, namely severity and mortality, was investigated with regard to statistical significance. The univariate approach showed that the muscle volume was significant for female (pseverity ≤ 0.001, pmortality ≤ 0.0001) and male patients (pseverity = 0.018, pmortality ≤ 0.0001) regarding the severity and mortality endpoints. For male patients, the intra- and intermuscular adipose tissue (IMAT) (p ≤ 0.0001), epicardial adipose tissue (EAT) (p ≤ 0.001) and pericardial adipose tissue (PAT) (p ≤ 0.0001) were significant regarding the severity outcome. With the mortality outcome, muscle (p ≤ 0.0001), IMAT (p ≤ 0.001), EAT (p = 0.011) and PAT (p = 0.003) remained significant. For female patients, bone (p ≤ 0.001), IMAT (p = 0.032) and PAT (p = 0.047) were significant in univariate analyses regarding the severity and bone (p = 0.005) regarding the mortality. Furthermore, the defined sarcopenia marker (p ≤ 0.0001, for female and male) was significant for both endpoints. The cardiac marker was significant for severity (pfemale = 0.014, pmale ≤ 0.0001) and for mortality (pfemale ≤ 0.0001, pmale ≤ 0.0001) endpoint for both genders. The multivariate logistic regression showed that the sarcopenia marker was significant (pseverity = 0.006, pmortality = 0.002) for both endpoints (ORseverity = 0.42, 95% CIseverity: 0.23–0.78, ORmortality = 0.34, 95% CImortality: 0.17–0.67). The cardiac marker showed significance (p = 0.018) only for the severity endpoint (OR = 1.42, 95% CI 1.06–1.90). The association between BCA-based sarcopenia and cardiac biomarkers and disease severity and mortality suggests that these biomarkers can contribute to the risk stratification of SARS-CoV-2 patients. Patients with a higher cardiac marker and a lower sarcopenia marker are at risk for a severe course or death. Whether those biomarkers hold similar importance for other pneumonia-related diseases requires further investigation. [ABSTRACT FROM AUTHOR]

Anorexia and fasting are host adaptations to acute infection, and induce a metabolic switch towards ketogenesis and the production of ketone bodies, including β-hydroxybutyrate (BHB)1–6. However, whether ketogenesis metabolically influences the immune response in pulmonary infections remains unclear. Here we show that the production of BHB is impaired in individuals with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) but not in those with influenza-induced ARDS. We found that BHB promotes both the survival of and the production of interferon-γ by CD4+ T cells. Applying a metabolic-tracing analysis, we established that BHB provides an alternative carbon source to fuel oxidative phosphorylation (OXPHOS) and the production of bioenergetic amino acids and glutathione, which is important for maintaining the redox balance. T cells from patients with SARS-CoV-2-induced ARDS were exhausted and skewed towards glycolysis, but could be metabolically reprogrammed by BHB to perform OXPHOS, thereby increasing their functionality. Finally, we show in mice that a ketogenic diet and the delivery of BHB as a ketone ester drink restores CD4+ T cell metabolism and function in severe respiratory infections, ultimately reducing the mortality of mice infected with SARS-CoV-2. Altogether, our data reveal that BHB is an alternative source of carbon that promotes T cell responses in pulmonary viral infections, and highlight impaired ketogenesis as a potential confounding factor in severe COVID-19.The ketone body β-hydroxybutyrate can be used as an alternative carbon source by T cells to maintain their function during severe respiratory viral infections, including infection with SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Background: A pre-existing anticoagulation treatment and predisposing diseases for thromboembolic events represent common problems in patients with sepsis or septic shock; however, these conditions are not addressed in current national guidelines for sepsis and septic shock. One of the aims of this nationwide survey in Germany was therefore to determine how intensive care physicians deal with these problems.Methods: From October 2019 to May 2020, we conducted a nationwide survey among German medical directors of intensive care units (ICU) addressing anticoagulation and drug-based prophylaxis of venous thromboembolism (VTE) in patients with sepsis and sepsis-induced coagulopathy. One focus was the procedure for patients with a pre-existing anticoagulation treatment or a previously known heparin-induced thrombocytopenia (HIT) type 2 (acute symptomatic vs. dating back years).Results: In most of the participating ICUs pre-existing anticoagulation is largely continued with low molecular weight heparin preparations or unfractionated heparin. In patients with pre-existing HIT type 2 both acute symptomatic and dating back years, argatroban represents the drug of choice. There is a high degree of variability in the definition of the target values, usually being well above the range for pure VTE prophylaxis.Conclusion: Data on the continuation of anticoagulation beyond VTE prophylaxis with a subsequently increased risk of bleeding in patients with sepsis and septic shock is limited and treatment decisions are in many cases subject to individual consideration by the practitioner. The results of our survey imply the need for a systematic work-up of this topic in order to support daily practice in many ICUs with the required evidence. [ABSTRACT FROM AUTHOR]

Purpose: Insufficient antimicrobial exposure is associated with worse outcomes in sepsis. We evaluated whether therapeutic drug monitoring (TDM)-guided antibiotic therapy improves outcomes. Methods: Randomized, multicenter, controlled trial from January 2017 to December 2019. Adult patients (n = 254) with sepsis or septic shock were randomly assigned 1:1 to receive continuous infusion of piperacillin/tazobactam with dosing guided by daily TDM of piperacillin or continuous infusion with a fixed dose (13.5 g/24 h if eGFR ≥ 20 mL/min). Target plasma concentration was four times the minimal inhibitory concentration (range ± 20%) of the underlying pathogen, respectively, of Pseudomonas aeruginosa in empiric situation. Primary outcome was the mean of daily total Sequential Organ Failure Assessment (SOFA) score up to day 10. Results: Among 249 evaluable patients (66.3 ± 13.7 years; female, 30.9%), there was no significant difference in mean SOFA score between patients with TDM (7.9 points; 95% CI 7.1–8.7) and without TDM (8.2 points; 95% CI 7.5–9.0) (p = 0.39). Patients with TDM-guided therapy showed a lower 28-day mortality (21.6% vs. 25.8%, RR 0.8, 95% CI 0.5–1.3, p = 0.44) and a higher rate of clinical (OR 1.9; 95% CI 0.5–6.2, p = 0.30) and microbiological cure (OR 2.4; 95% CI 0.7–7.4, p = 0.12), but these differences did not reach statistical significance. Attainment of target concentration was more common in patients with TDM (37.3% vs. 14.6%, OR 4.5, CI 95%, 2.9–6.9, p < 0.001). Conclusion: TDM-guided therapy showed no beneficial effect in patients with sepsis and continuous infusion of piperacillin/tazobactam with regard to the mean SOFA score. Larger studies with strategies to ensure optimization of antimicrobial exposure are needed to definitively answer the question. [ABSTRACT FROM AUTHOR]

Copyright of Anaesthesist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Recent data suggest that the type of anesthesia used during the resection of solid tumors impacts the long-term survival of patients favoring total-intravenous-anesthesia (TIVA) over inhalative-anesthesia (INHA). Here we sought to query this impact on survival in patients undergoing resection of glioblastoma (GBM). All patients receiving elective resection of a newly diagnosed, isocitrate-dehydrogenase-1-(IDH1)-wildtype GBM under general anesthesia between January 2010 and June 2017 in the Department of Neurosurgery, Heidelberg University Hospital, were included. Patients were grouped according to the applied anesthetic technique. To adjust for potential prognostic confounders, patients were matched in a 1:2 ratio (TIVA vs. INHA), taking into account the known prognostic factors: age, extent of resection, O-6-methylguanine-DNA-methyltransferase-(MGMT)-promoter-methylation-status, pre-operative Karnofsky-performance-index and adjuvant radio- and chemotherapy. The primary endpoint was progression-free-survival (PFS) and the secondary endpoint was overall-survival (OS). In the study period, 576 patients underwent resection of a newly diagnosed, IDH-wildtype GBM. Patients with incomplete follow-up-data, on palliative treatment, having emergency or awake surgery; 54 patients remained in the TIVA-group and 417 in the INHA-group. After matching, 52 patients remained in the TIVA-group and 92 in the INHA-group. Median PFS was 6 months in both groups. The median OS was 13.5 months in the TIVA-group and 13.0 months in the INHA-group. No significant survival differences associated with the type of anesthesia were found either before or after adjustment for known prognostic factors. This retrospective study supports the notion that the current anesthetic approaches employed during the resection of IDH-wildtype GBM do not impact patient survival. [ABSTRACT FROM AUTHOR]

Background: In the context of sepsis and septic shock, coagulopathy often occurs due to the close relationship between coagulation and inflammation. Sepsis-induced coagulopathy (SIC) is the most severe and potentially fatal form. Anticoagulants used in prophylactic or therapeutic doses are discussed to potentially exert beneficial effects in patients with sepsis and/or SIC; however, due to the lack of evidence recent guidelines are limited to recommendations for drug prophylaxis of venous thromboembolism (VTE), while treatment of SIC has not been addressed.Methods: In order to determine the status quo of VTE prophylaxis as well as treatment of SIC in German intensive care units (ICU), we conducted a Germany-wide online survey among heads of ICUs from October 2019 to May 2020. In April 2020, the survey was supplemented by an additional block of questions on VTE prophylaxis and SIC treatment in coronavirus disease 2019 (COVID-19) patients.Results: A total of 67 senior doctors took part in the survey. The majority (n = 50; 74.6%) of the responses were from ICU under the direction of an anesthesiologist and/or a department of anesthesiology. Most of the participants worked either at a university hospital (n = 31; 47.8%) or an academic teaching hospital (n = 27; 40.3%). The survey results show a pronounced heterogeneity in clinical practice with respect to the prophylaxis of VTE as well as SIC treatment. In an exemplary case of pneumogenic sepsis, low molecular weight heparins (LMWH) were by far the most frequently mentioned group of medications (n = 51; 76.1% of the responding ITS). In the majority of cases (n = 43; 64.2%), anti-FXa activity is not monitored with the use of LMWH in prophylaxis doses. Unfractionated heparin (UFH) was listed as a strategy for VTE prophylaxis in 37.3% of the responses (n = 25). In an exemplary case of abdominal sepsis 54.5% of the participants (n = 36; multiple answers possible) stated the use of UFH or LMWH and UFH with dosage controlled by PTT is used on two participating ICUs. The anti-FXa activity under prophylactic anticoagulation with LMWH is monitored in 7 participating clinics (10.6%) in abdominal sepsis. Systematic screening for sepsis-associated coagulation disorders does not take place in most hospitals and patterns in the use of anticoagulants show significant variability between ICUs. In the case of COVID-19 patients, it is particularly noticeable that in three quarters of the participating ICUs the practice of drug-based VTE prophylaxis and SIC treatment does not differ from that of non-COVID-19 patients.Conclusion: The heterogeneity of answers collected in the survey suggests that a systematic approach to this topic via clinical trials is urgently needed to underline individualized patient care with the necessary evidence. [ABSTRACT FROM AUTHOR]

Purpose: Standard dosing and intermittent bolus application (IB) are important risk factors for pharmacokinetic (PK) target non-attainment during empirical treatment with β-lactams in critically ill patients, particularly in those with sepsis and septic shock. We assessed the effect of therapeutic drug monitoring-guided (TDM), continuous infusion (CI) and individual dosing of piperacillin/tazobactam (PIP) on PK-target attainment in critically ill patients. Methods: This is a retrospective, single-center analysis of a database including 484 patients [933 serum concentrations (SC)] with severe infections, sepsis and septic shock who received TDM-guided CI of PIP in the intensive care unit (ICU) of an academic teaching hospital. The PK-target was defined as a PIP SC between 33 and 64 mg/L [fT > 2–4 times the epidemiological cutoff value (ECOFF) of Pseudomonas aeruginosa (PSA)]. Results: PK-target attainment with standard dosing (initial dose) was observed in 166 patients (34.3%), whereas only 49 patients (10.1%) demonstrated target non-attainment. The minimum PK-target of ≥ 33 mg/L was overall realized in 89.9% (n = 435/484) of patients after the first PIP dose including 146 patients (30.2%) with potentially harmful SCs ≥ 100 mg/L. Subsequent TDM-guided dose adjustments significantly enhanced PK-target attainment to 280 patients (62.4%) and significantly reduced the fraction of potentially overdosed (≥ 100 mg/L) patients to 4.5% (n = 20/449). Renal replacement therapy (RRT) resulted in a relevant reduction of PIP clearance (CLPIP): no RRT CLPIP 6.8/6.3 L/h (median/IQR) [SCs n = 752, patients n = 405], continuous veno-venous hemodialysis (CVVHD) CLPIP 4.3/2.6 L/h [SCs n = 160, n = 71 patients], intermittent hemodialysis (iHD) CLPIP 2.6/2.3 L/h [SCs n = 21, n = 8 patients]). A body mass index (BMI) of > 40 kg/m2 significantly increased CLPIP 9.6/7.7 L/h [SC n = 43, n = 18 patients] in these patients. Age was significantly associated with supratherapeutic PIP concentrations (p < 0.0005), whereas high CrCL led to non-target attainment (p < 0.0005). Patients with target attainment (33–64 mg/L) within the first 24 h exhibited the lowest hospital mortality rates (13.9% [n = 23/166], p < 0.005). Those with target non-attainment demonstrated higher mortality rates (≤ 32 mg/L; 20.8% [n = 10/49] ≥ 64 mg/L; 29.4% [n = 79/269]). Conclusion: TDM-guided CI of PIP is safe in critically ill patients and improves PK-target attainment. Exposure to defined PK-targets impacts patient mortality while lower and higher than intended SCs may influence the outcome of critically ill patients. Renal function and renal replacement therapy are main determinants of PK-target attainment. These results are only valid for CI of PIP and not for prolonged or intermittent bolus administration of PIP. [ABSTRACT FROM AUTHOR]

Purpose: To assess the putative impact of peridural analgesia on oncological outcome in patients undergoing resection of stages I–IV colon cancer. Methods: In a single-center study, 876 patients undergoing resection for primary colon cancer (AJCC stages I–IV) between 2001 and 2014 were analyzed. Mean follow-up of the entire cohort was 4.2 ± 3.5 years. Patients who did and did not receive peridural analgesia were compared using Cox regression and propensity score analyses. Results: Overall, 208 patients (23.7%) received peridural analgesia. Patients' characteristics were biased with regard to the use of peridural analgesia (propensity score 0.296 ± 0.129 vs. 0.219 ± 0.108, p < 0.001). After propensity score matching, the use of peridural analgesia had no impact on overall (HR 0.81, 95% CI 0.59–1.11, p = 0.175), cancer-specific (HR 0.72, 95% CI 0.48–1.09, p = 0.111), and disease-free survival (HR 0.89, 95% CI 0.66–1.19, p = 0.430). The 5-year overall survival after propensity score matching was 60.9% (95% CI 54.8–67.7%) for patients treated with peridural analgesia compared with 54.1% (95% CI 49.5–59.1%) for patients not treated with peridural analgesia. Cancer-specific and disease-free survival showed similar non-significant results. Conclusions: Peridural analgesia in patients after colon cancer resection was not associated with a better oncological outcome after risk adjusting in multivariable Cox regression and propensity score analyses. Hence, oncological outcome should not serve as a reason for the use of peridural analgesia in patients with colon cancer. [ABSTRACT FROM AUTHOR]

Purpose: Despite antifungal prophylaxis following liver transplantation (LTX), patients are at risk for the development of subsequent opportunistic infections, such as an invasive fungal disease (IFD). However, culture-based diagnostic procedures are associated with relevant weaknesses. Methods: Culture and next-generation sequencing (NGS)-based fungal findings as well as corresponding plasma levels of ß-D-glucan (BDG), galactomannan (GM), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-2, -4, -6, -10, -17A and mid-regional proadrenomedullin (MR-proADM) were evaluated in 93 patients at 6 consecutive time points within 28 days following LTX. Results: A NGS-based diagnostic approach was shown to be suitable for the early identification of fungal pathogens in patients following LTX. Moreover, MR-proADM and IL-17A in plasma proved suitable for the identification of patients with an IFD. Conclusion: Plasma measurements of MR-proADM and IL-17A as well as a NGS-based diagnostic approach were shown to be attractive methodologies to attenuate the weaknesses of routinely used culture-based diagnostic procedures for the determination of an IFD in patients following LTX. However, an additional confirmation within a larger multicenter trial needs to be recommended. Trial registration: German Clinical Trials Register: DRKS00005480. [ABSTRACT FROM AUTHOR]

Introduction: Numerous extended donor criteria (EDC) have been identified in liver transplantation (LT), but different EDC have different impacts on graft and patient survival. This study aimed to identify major EDC (maEDC) that were best able to predict the outcome after LT and to examine the plausibility of an allocation algorithm based on these criteria.Methods: All consecutive LTs between 12/2006 and 03/2014 were included (n = 611). We analyzed the following EDC: donor age > 65 years, body mass index > 30, malignancy and drug abuse history, intensive care unit stay/ventilation > 7 days, aminotransferases > 3 times normal, serum bilirubin > 3 mg/dL, serum Na+ > 165 mmol/L, positive hepatitis serology, biopsy-proven macrovesicular steatosis (BPS) > 40%, and cold ischemia time (CIT) > 14 h. We analyzed hazard risk ratios of graft failure for each EDC and evaluated primary non-function (PNF). In addition, we analyzed 30-day, 90-day, 1-year, and 3-year graft survival. We established low- and high-risk graft (maEDC 0 vs. ≥ 1) and recipient (labMELD < 20 vs. ≥ 20) groups and compared the post-LT outcomes between these groups.Results: BPS > 40%, donor age > 65 years, and CIT > 14 h (all p < 0.05) were independent predictors of graft failure and patient mortality and increased PNF, 30-day, 90-day, 1-year, and 3-year graft failure rates. Three-year graft and patient survival decreased in recipients of ≥ 1 maEDC grafts (all p < 0.05) and LT of high-risk grafts into high-risk recipients yielded worse outcomes compared with other groups.Conclusion: Donor age > 65 years, BPS > 40%, and CIT > 14 h are major EDC that decrease short and 3-year graft survival, and 3-year patient survival. An allocation algorithm based on maEDC and labMELD is therefore plausible. [ABSTRACT FROM AUTHOR]

Purpose: Anastomotic leakage is the most frequent cause of postoperative mortality following esophageal surgery. However, no gold standard for diagnosing and managing leakage has been established. Continuous clinical judgment is extremely important; therefore, to optimize the management of leakage, we established a special group for decision-making in cases of suspected leakage in the early postoperative period. Methods: Between January 2010 and December 2016, 234 consecutive patients underwent elective esophageal resection with a thoracoabdominal incision. In 2014, we established a group consisting of a surgeon, surgical endoscopist, and anesthesiologist for decision-making in cases of suspected leakage. They discussed emerging problems and decided on further diagnostics or therapy. The data were documented prospectively and compared to the years prior to 2014. Results: Two hundred and thirty-four consecutive patients were enrolled in the study, 110 in the years 2010-2013 (group A), and 124 in the years 2014-2016 (group B). Neither patients' characteristics nor the rate of anastomotic leakage differed significantly between the two study groups. The hospital mortality rate was 10% (11 patients) in group A and 4.8% (six patients) in group B. Most interestingly, mortality due to anastomotic leakage was 35% in group A (9/26), whereas it decreased significantly to 6.5% (2/31 patients) ( P < 0.001) in group B. Conclusions: Our data clearly demonstrated that optimizing the management of anastomotic leakage by making team decisions can lead to a significant decrease in mortality. [ABSTRACT FROM AUTHOR]

Introduction: Advanced glycation endproducts (AGEs) are well-known inflammatory mediators, which are recognized by immune cells through their corresponding receptor RAGE and have been shown to participate in the pathophysiology of a variety of acute as well as chronic inflammatory diseases. Nevertheless, no data are available on the aftermath of AGE recognition on immune cells. Materials and methods: We used the monocytic cell line MonoMac6 as well as primary human monocytes for double stimulation experiments. We measured secreted as well as intracellular levels of TNF-α using ELISA and flow cytometry. In addition, gene expression of surface receptors (RAGE and TLR4) and TNF were measured by qPCR. Results: Stimulation with AGE leads to a dose-dependent induction of self- and cross-tolerance in both primary monocytes as well as the MonoMac6 cell line. The AGE tolerance depended neither on a decreased expression of RAGE or TLR4, nor on a decrease of TNF-α expression. Nevertheless, intracellular TNF-α was decreased, hinting towards a posttranscriptional regulation. Conclusion: High levels of AGEs are capable to activate immune cells at first, but induce a secondary state of hypo-responsiveness in these cells. Based on the origin of its causal agent, we propose this phenomenon to be 'metabolic tolerance'. [ABSTRACT FROM AUTHOR]

Correction to: Intensive Care Medicine (2022) 48:311-321 https://doi.org/10.1007/s00134-021-0... In this article, the affiliation details for Dominic Witzke were incorrectly given as 'Department of Infectious Diseases, Evangelisches Klinikum Bethel, Bielefeld, Germany', but should have read instead 'Department of Anaesthesiology, Intensive Care, Protestant Hospital of the Bethel Foundation, University Hospital of Bielefeld, Campus Bielefeld-Bethel, University of Bielefeld, Germany'. Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s00134-022-06668-3. [Extracted from the article]

These parameters were regarded as maEDC, and their effects on graft and patient survival were analyzed." These parameters were regarded as maEDC, and their effects on graft and patient survival were analyzed." The original article can be found online at https://doi.org/10.1007/s00423-018-1704-z B Correction to: Langenbeck's Archives of Surgery (2018) 403:719-731 b https://doi.org/10.1007/s00423-018-1704-z The original version of this article unfortunately contained a small error on pages 722-723 of the manuscript (paragraph "Major EDC"). [Extracted from the article]

Objective: There is continuing concern on the influence of hydroxethyl starch (HES) on renal function.Design: Prospective, randomized study.Setting: University-affiliated medical center.Patients: Forty consecutive patients aged >70 years undergoing cardiac surgery using cardiopulmonary bypass.Interventions: Either low-molecular HES (mean molecular weight: 130 kD) with low degree of substitution (0.4) (6% HES 130/0.4) (n=20) or gelatin ( n=20) was given after induction of anesthesia until the 2nd postoperative day (POD) to keep central venous pressure between 12-14 mmHg.Measurements and Results: Creatinine clearance (CC) and fractional sodium clearance (FSC) were measured. N-acetyl-beta-D-glucosamidase, alpha-1-microglobulin, glutathione transferase-pi, and glutathione transferase-alpha were measured from urine specimens. Measurements were made after induction of anesthesia, at the end of surgery, and at the first and the second POD. More gelatin (total: 4150+/-490 ml) than HES 130/0.4 (total: 3450+/-450 ml) was infused within the study. CC and FSC were without differences between the two groups. All measured kidney-specific proteins were almost within normal range at baseline. They increased significantly after surgery, however, without significant group differences. At the 2nd POD, kidney-specific proteins had returned almost to normal values. None of the patients developed acute renal failure.Conclusions: Sensitive markers of kidney dysfunction increased in our elderly patients indicating moderate alterations in kidney integrity during cardiac surgery. The two volume replacement regimens did not differ with regard to kidney integrity in elderly patients undergoing cardiac surgery. [ABSTRACT FROM AUTHOR]

Ein Erratum zu dieser Publikation wurde veröffentlicht: https://doi.org/10.1007/s00101-021-00916-9 [ABSTRACT FROM AUTHOR]

Podocyte injury has recently been described as unifying feature in idiopathic nephrotic syndromes (INS). Puumala hantavirus (PUUV) infection represents a unique RNA virus-induced renal disease with significant proteinuria. The underlying pathomechanism is unclear. We hypothesized that PUUV infection results in podocyte injury, similar to findings in INS. We therefore analyzed standard markers of glomerular proteinuria (e.g. immunoglobulin G [IgG]), urinary nephrin excretion (podocyte injury) and serum levels of the soluble urokinase plasminogen activator receptor (suPAR), a proposed pathomechanically involved molecule in INS, in PUUV-infected patients. Hantavirus patients showed significantly increased urinary nephrin, IgG and serum suPAR concentrations compared to healthy controls. Nephrin and IgG levels were significantly higher in patients with severe proteinuria than with mild proteinuria, and nephrin correlated strongly with biomarkers of glomerular proteinuria over time. Congruently, electron microcopy analyses showed a focal podocyte foot process effacement. suPAR correlated significantly with urinary nephrin, IgG and albumin levels, suggesting suPAR as a pathophysiological mediator in podocyte dysfunction. In contrast to INS, proteinuria recovered autonomously in hantavirus patients. This study reveals podocyte injury as main cause of proteinuria in hantavirus patients. A better understanding of the regenerative nature of hantavirus-induced glomerulopathy may generate new therapeutic approaches for INS. [ABSTRACT FROM AUTHOR]

Major traumatic injury (MTI), a life-threatening condition requiring prompt medical intervention, is associated with an extensive inflammatory response often resulting in multiple organ dysfunction. Early stratification of trauma severity and the corresponding inflammation may help optimize resources at the intensive care unit (ICU). The cholinergic system counters inflammation by quickly modulating the immune response. Serum cholinesterase (butyrylcholinesterase, BChE) is an enzyme that hydrolyses acetylcholine. We tested whether a change in the BChE activity correlates with the morbidity and the length of ICU stay. Blood samples from 10 healthy volunteers and 44 patients with MTI were gathered at hospital admission, followed by measurements 12, 24 and 48 hours later. Point-of-care approach was used to determine the BChE activity. Disease severity was assessed by clinical scoring performed within 24 hours following hospital admission. BChE activity, measured at hospital admission, showed a significant and sustained reduction and correlated with disease severity scores obtained 24 hours following admission. BChE activity, obtained at hospital admission, correlated with the length of ICU stay. Bedside measurement of BChE activity, as a complementary addition to established procedures, might prove useful in the primary assessment of the disease severity and might therefore optimize therapy in the ICU. [ABSTRACT FROM AUTHOR]

Background: Septic coagulopathy represents a very dynamic disease entity, tilting from initial hypercoagulability towards a subsequent hypocoagulable disease state, entitled overt disseminated intravascular coagulation. Acute fibrinolysis shutdown has recently been described to be a crucial component of initial hypercoagulability in critically ill patients, although the underlying pathomechanisms, the specific temporal kinetics and its outcome relevance in patients with sepsis remain to be determined.Methods: In total, 90 patients (30 with septic shock, 30 surgical controls and 30 healthy volunteers) were enrolled. Blood samples were collected at sepsis onset or prior and immediately after the surgical procedure as well as 3 h, 6 h, 12 h, 24 h, 48 h and 7 d later, whereas blood samples from healthy volunteers were collected once. Besides viscoelastic and aggregometric point-of-care testing (POCT), enzyme-linked immunosorbent and thrombin generation assays and liquid chromatography-mass spectrometry-based measurements were performed.Results: As assessed by viscoelastic POCT, fibrinolysis shutdown occurred early in sepsis. Significant increases in tissue plasminogen activator had no effect on thromboelastometrical lysis indices (LIs). Contrariwise, plasminogen activator inhibitor-1 was already significantly increased at sepsis onset, which was paralleled by significantly increased LIs in patients suffering from septic shock in comparison with both control groups. This effect persisted throughout the 7-day observation period and was most pronounced in severely ill as well as non-surviving septic patients. Thromboelastometrical LI, therefore, proved to be suitable for early diagnosis [e.g. LI 45 min: area under the curve (AUC) up to 0.933] as well as prognosis (e.g. LI 60 min: AUC up to 1.000) of septic shock.Conclusions: Early inhibition of plasminogen activation leads to acute fibrinolysis shutdown with improved clot stability and is associated with increased morbidity and mortality in septic patients.Trial registration This study was approved by the local ethics committee (Ethics Committee of the Medical Faculty of Heidelberg; Trial-Code No. S247-2014/German Clinical Trials Register (DRKS)-ID: DRKS00008090; retrospectively registered: 07.05.2015). All study patients or their legal representatives signed written informed consent. [ABSTRACT FROM AUTHOR]

The article informs that the article "Influence of two different volume replacement regimens on renal function in elderly patients undergoing cardiac surgery: comparison of a new starch preparation with gelatin," in a previous issue, has been retracted.