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Introduction A need exists to improve the efficiency of clinical trials in burn care. The objective of this study was to validate “Persistent Organ Dysfunction” plus death as endpoint in burn patients and to demonstrate its statistical efficiency. Methods This secondary outcome analysis of a dataset from a prospective international multicenter RCT (RE-ENERGIZE) included patients with burned total body surface area >20% and a 6-month follow-up. Persistent organ dysfunction was defined as persistence of organ dysfunction with life-supportiing technologies and ICU care. Results In the 539 included patients, the prevalence of 0p p+ pdeath was 40% at day 14 and of 27% at day 28. At both timepoints, survivors with POD (vs. survivors without POD) had a higher mortality rate, longer ICU- and hospital-stays, and a reduced quality of life. POD + death as an endpoint could result in reduced sample size requirements for clinical trials. Detecting a 25% relative risk reduction in 28-day mortality would require a sample size of 4492 patients, whereas 1236 patients would be required were 28-day POD + death used. Conclusions POD + death represents a promising composite outcome measure that may reduce the sample size requirements of clinical trials in severe burns patients. Further validation in larger clinical trials is warranted. Study type Prospective cohort study, level of evidence: II

Summary Background & aims Burn patients pose a number of clinical challenges for doctors and dietitians to achieve optimal nutrition practice. The objective of this study was to describe nutrition practices in burn center intensive care units (ICUs) compared to the most recent ESPEN and SCCM/ASPEN guidelines (hereafter referenced as “the Guidelines”) and highlight the variation in practice and what is “best achievable.” Methods In 2014–15, we prospectively enrolled 283 mechanically ventilated patients who were admitted to one of 14 burn ICUs for at least 72 h. Data collected included information on the estimation of energy and protein requirements, their actual delivery as well as route and time of feeding, and administration of micronutrients. We describe site practices and data per patient-day. Results Adherence to the Guidelines for the use of enteral nutrition (EN) over parenteral nutrition (PN) was 90.5% of patient-days (site range 79.2%–97.0%). However, adherence to the Guidelines for the measurement of energy requirements was 6.0% of patient-days (site range 0.0%–93.3%), supplementation with glutamine took place in 22.4% of patient-days (site range 0.0%–61.8%). Provision of 80% of energy requirements within 48–72 h was achieved in 35.3% of patients (site range 0.0%–80.0%), and provision of 80% of protein needs within 48–72 h was achieved in 34.3% of patients (site range 0.0%–80.0%). Average nutritional adequacy was 64.9 ± 40.0% for energy (best site: 80.2%, worst site: 42.0%) and 65.6 ± 42.1% for protein (best site: 87.3%, worst site: 43.6%). Conclusion The present findings indicate that despite high adherence to providing EN over PN, there is still a large gap between many recommendations and clinical practice, and the achievement of nutrition goals for patients in burn centers is suboptimal.

This review provides an overview for health care teams involved in the perioperative care of cardiac surgery patients. The intention is to summarize key determinants of delirium, its impact on short- and long-term outcomes as well as to discuss effective management strategies. The first component of this review examines the prevalence and the factors associated with an increased risk of postoperative delirium. A multitude of predisposing (eg, baseline vulnerability and comorbidities) and precipitating (eg, type of cardiac surgery and postoperative care) factors that contribute to the occurrence of delirium are discussed.

Cardiac surgery is performed more often in a population with an increasing number of comorbidities. Although these surgeries can be lifesaving, they disturb homeostasis and may induce a temporary overall loss of physiologic function. The required postoperative intensive care unit and hospital stay often lead to a mid- to long-term decline of nutritional and physical status, mental health, and health-related quality of life. Prehabilitation before elective surgery might be an opportunity to optimize the state of the patient. This article discusses current evidence and potential effects of preoperative optimization of nutrition and physical status before cardiac surgery.

OBJECTIVE Aneurysmal subarachnoid hemorrhage (aSAH) initiates a deleterious cascade activating multiple inflammatory processes, which can contribute to delayed cerebral ischemia (DCI). Procalcitonin (PCT) is an established marker for sepsis treatment monitoring, and its time course in the context of DCI after aSAH remains unclear. The aim of this trial was to assess the predictive and confirmative value of PCT levels in the context of DCI. METHODS All patients admitted to the authors’ institution with aSAH between 2014 and 2018 were prospectively screened for eligibility. Daily PCT levels were recorded alongside relevant aSAH characteristics. The predictive and confirmative values of PCT levels were assessed using a receiver operating characteristic and area under the curve (AUC) analysis. The course of PCT levels around the DCI event was evaluated in an infection-free subgroup of patients. RESULTS A total of 132 patients with aSAH were included. Early PCT levels (first 3 days post-aSAH) had a low predictive value for the development of DCI (AUC 0.661, standard error [SE] 0.050; p = 0.003) and unfavorable long-term outcome (i.e., Glasgow Outcome Scale–Extended scores 1–4; AUC 0.674, SE 0.054; p = 0.003). In a subgroup analysis of infection-free patients (n = 72), PCT levels were higher in patients developing DCI (p = 0.001) and DCI-related cerebral infarction (p = 0.002). PCT concentrations increased gradually after DCI and decreased with successful intervention. In refractory cases progressing to cerebral infarction, PCT levels showed a secondary increase. CONCLUSIONS Early higher PCT levels were associated with the later development of DCI and unfavorable outcome. Analysis of PCT beyond the first couple of days after hemorrhage is hampered by nosocomial infections. In infection-free patients, however, PCT levels rise during DCI and an additional increase develops in patients developing cerebral infarction. Clinical trial registration no.: NCT02142166 (clinicaltrials.gov)

While medical nutrition therapy is an essential part of the care for critically ill patients, uncertainty exists about the right form, dosage, timing and route in relation to the phases of critical illness. As enteral nutrition (EN) is often withheld or interrupted during the intensive care unit (ICU) stay, combined EN and parenteral nutrition (PN) may represent an effective and safe option to achieve energy and protein goals as recommended by international guidelines. We hypothesise that critically ill patients at high nutritional risk may benefit from such a combined approach during their stay on the ICU. Therefore, we aim to test if an early combination of EN and high-protein PN (EN+PN) is effective in reaching energy and protein goals in patients at high nutritional risk, while avoiding overfeeding. This approach will be tested in the here-presented EFFORTcombo trial. Nutritionally high-risk ICU patients will be randomised to either high (≥2·2 g/kg per d) or low protein (≤1·2 g/kg per d). In the high protein group, the patients will receive EN+PN; in the low protein group, patients will be given EN alone. EN will be started in accordance with international guidelines in both groups. Efforts will be made to reach nutrition goals within 48–96 h. The efficacy of the proposed nutritional strategy will be tested as an innovative approach by functional outcomes at ICU and hospital discharge, as well as at a 6-month follow-up.

Background and objectives Coronary artery disease (CAD) is the number one cause of death worldwide. The If channel inhibitor ivabradine serves as second line medication for the CAD leading symptom angina pectoris. This systematic review and meta-analysis assess the existing evidence of ivabradine in angina pectoris. Methods We systematically searched MEDLINE, Embase, CENTRAL, and Web of Science (September 2019) for randomized controlled trials (RCTs) that compared ivabradine versus placebo, standard therapy (ST) or other anti-anginal drugs. Two review authors independently assessed trials for inclusion and performed data extraction. We completed a 'risk of bias' assessment for all studies and assessed quality of the trial evidence using the Grading of Recommendations Assessment, Development and Evaluation methodology. We meta-analysed data were applicable and calculated mean differences (MDs) and risk ratios using a random-effects model. Results A total of 11 RCTs (n=16,039) were included. Compared to placebo/ST, we found significant effects on the frequency of hospitalisation in a small cohort (n=90; hazard ratio [HR], 0.19; 95% confidence interval [CI], 0.04, -0.92; p=0.04), but no effects on cardiovascular mortality (n=19,102; HR, 1.10; 95% CI, 0.94, 1.28; p=0.25) or the frequency of angina pectoris episodes (n=167; weighted MD, -1.06; 95% CI, -2.74, -0.61; p=0.21). Conclusions The present work makes an important contribution to optimal patient care in angina pectoris by complementing the current European Society of Cardiology guideline-recommending class IIa with evidence level B-decisively with 8 further studies.

Der ethische Bezugsrahmen zur Durchfuhrung einer Flussigkeitstherapie in der palliativmedizinischen Versorgung am Lebensende kann sehr unterschiedlich gewahlt werden. Welche ethischen Implikationen gilt es wahrend einer Dehydration am Lebensende zu beachten und gibt es besondere Anforderungen im Umgang mit der „terminalen“ Dehydration? Es wurde eine umfassende Literatursuche durchgefuhrt, um relevante Artikel in englischer und deutscher Sprache zu identifizieren. Unsere Schlussfolgerungen reprasentieren eher eine Haltung als eine evidenzbasierte Position – eine Tatsache, die auf den zugrunde liegenden normativen und ethischen Bezugen basiert, die einer statistischen Auswertung kaum zuganglich sind. Unsere ethischen Erwagungen werden vom Fehlen einer klaren Evidenzlage gepragt, die es nach unserer Auffassung auch am Lebensende nicht rechtfertigt, sich von etablierten Konzepten der klinisch assistierten Flussigkeitszufuhr („clinically assisted hydration“, CAH) zu entfernen, solange therapeutische Masnahmen wirksam umgesetzt werden konnen. Die „permissive“ Dehydration darf am Lebensende nicht als eine Option zur Verkurzung des Sterbeprozesses betrachtet werden. In der Palliativmedizin ist die Dehydration auch weiterhin als „Symptom“ zu betrachten, das zu „kontrollieren“ ist, solange dieses mit therapeutischen Mitteln beherrscht werden kann und solange der Patient diesem Vorgehen nicht ablehnend gegenubersteht. Bleibt die Dehydration aber therapeutisch refraktar, ist es gerechtfertigt, die CAH entweder nicht zu initiieren oder die laufende Therapie zu stoppen.

Der rechtliche Bezugsrahmen zur Durchfuhrung einer Flussigkeitstherapie in der palliativmedizinischen Versorgung am Lebensende kann auf verschiedenen Kontinenten und sogar in benachbarten Landern sehr unterschiedlich sein. Welche rechtlichen Implikationen mussen in Deutschland im Umgang mit der „terminalen“ Dehydration beachtet werden? Es wurden relevante Publikationen in englischer und deutscher Sprache identifiziert. Insbesondere wurden die in Deutschland gultigen Empfehlungen herangezogen und mit den Vorgehensweisen in England und Kanada verglichen. Unsere rechtlichen Erwagungen entsprechen den Empfehlungen der Bundesarztekammer. Als zentrale Bestandteile sind die Patientenautonomie, die bestmogliche Symptomkontrolle und die standige therapeutische Nutzen-Risiko-Abschatzung zu nennen. Die Dehydration ist danach auch weiterhin als „Symptom“ zu betrachten, das zu „kontrollieren“ ist, solange dieses mit therapeutischen Mitteln beherrscht werden kann und solange der Patient diesem Vorgehen nicht ablehnend gegenubersteht. Bleibt die Dehydration aber therapeutisch refraktar, ist es gerechtfertigt, die klinisch assistierte („Clinically assisted hydration“, CAH) entweder nicht zu initiieren oder die laufende Therapie zu stoppen. Diesem Vorgehen steht das in Kanada praktizierte „shared decision-making model“ diametral gegenuber, bei dem eine paternalistische Entscheidungsfindung moglich ist, sofern die Patienten oder Angehorigen schlecht informiert und unvorbereitet erscheinen, um nach Expertenmeinung „richtig“ zu entscheiden. Eine nichtrefraktare Dehydration am Lebensende darf nach deutschem Recht nicht untherapiert bleiben und darf nicht als Option zur Verkurzung des Sterbeprozesses genutzt werden, wenn die Entstehung einer Dehydration nicht dem Patientenwillen entspricht oder dieser Wille nicht ermittelbar ist.

Cardiac surgery (CSX) can be lifesaving in elderly patients (age &ge, 80 years) but may still be associated with complications and functional decline. Frailty represents a determinant to outcomes in critically ill patients, but little is known about its influence on elderly CSX-patients. This is a secondary exploratory analysis of a multi-center, prospective observational cohort study of 610 elderly patients admitted to the ICU and followed for one year to document long-term outcomes. CSX-ICU-patients (n = 49) were compared to surgical ICU patients (n = 184) with regard to demographics, frailty, and outcomes. Of all surgical patients, 102 (43%) were considered vulnerable or frail. The subdistribution hazard ratio (SHR) of time to discharge home (TTDH) for vulnerable/frail vs. fit/well patients was 0.54 (95% confidence interval (CI), 0.34, 0.86, p = 0.007). The p-value for effect modification between surgery group (CSX vs. surgical ICU patients) and Clinical Frailty Scale (CFS) group was not significant (p = 0.37) suggesting that the observed difference in the CFS effect between the CSX and surgical ICU patients is consistent with random error. A further subgroup analysis shows that among surgical ICU patients, the SHR of time to discharge home (TTDH) for vulnerable/frail vs. fit/well patients was 0.49 (95% CI, 0.29, 0.83) while the corresponding SHR for CSX patients was 0.77 (0.32&ndash, 1.88). In conclusion, preoperative frailty reduced the rate of discharge to home in both surgical and CSX patients, but a larger sample of CSX patients is needed to adequately address this question in this patient group.

BMJ Open 11(11), e053148 (2021). doi:10.1136/bmjopen-2021-053148, Published by BMJ Publishing Group, London

OBJECTIVES To conduct a systematic review and meta-analysis to evaluate the impact of IV vitamin C on outcomes in critically ill patients. DATA SOURCES Systematic search of MEDLINE, EMBASE, CINAHL, and the Cochrane Register of Controlled Trials. STUDY SELECTION Randomized controlled trials testing IV vitamin C in critically ill patients. DATA ABSTRACTION Two independent reviewers abstracted patient characteristics, treatment details, and clinical outcomes. DATA SYNTHESIS Fifteen studies involving 2,490 patients were identified. Compared with placebo, IV vitamin C administration is associated with a trend toward reduced overall mortality (relative risk, 0.87; 95% CI, 0.75-1.00; p = 0.06; test for heterogeneity I2 = 6%). High-dose IV vitamin C was associated with a significant reduction in overall mortality (relative risk, 0.70; 95% CI, 0.52-0.96; p = 0.03), whereas low-dose IV vitamin C had no effect (relative risk, 0.94; 95% CI, 0.79-1.07; p = 0.46; test for subgroup differences, p = 0.14). IV vitamin C monotherapy was associated with a significant reduction in overall mortality (relative risk, 0.64; 95% CI, 0.49-0.83; p = 0.006), whereas there was no effect with IV vitamin C combined therapy. No trial reported an increase in adverse events related to IV vitamin C. CONCLUSIONS IV vitamin C administration appears safe and may be associated with a trend toward reduction in overall mortality. High-dose IV vitamin C monotherapy may be associated with improved overall mortality, and further randomized controlled trials are warranted.

Background: Macrophage migration inhibitory factor (MIF) is an important stress-regulating mediator of acute ischemia/reperfusion (I/R) injury and ischemic conditioning. The present study aimed to investigate whether MIF is involved in the effects of remote ischemic conditioning (RIC) in a rat model of orthotopic liver transplantation (OLT). Methods: OLTs were performed in male Lewis rats (245 g-340 g). Recipients were allocated in a randomized fashion into three experimental groups: remote preconditioning-RIPC, remote post-conditioning-RIPOST, control. RIC was applied as 4x5-5 min I/R via clamping of the infrarenal aorta. Animals were followed for 1, 3, 24, 168 h post-reperfusion (n = 6 recipient/group/time point). Graft micro- and macrocirculation and hepatocellular damage were assessed. Messenger ribonucleic acid (mRNA) expression, serum, and tissue protein levels of MIF, as well as additional markers of I/R injury, were measured. Results: RIC resulted in a prominent downregulation of MIF mRNA, serum, and tissue protein. Compared with control, hepatocellular damage was significantly mitigated after RIPC or RIPOST (serum ALT; RIPC, RIPOST vs. Control, P = 0.008, P = 0.030, respectively). Graft circulation was better preserved in the RIC groups. Furthermore, there was a significant positive correlation between serum MIF and transaminase levels (r = 0.330; P = 0.02). RIC showed a significant effect on iNOS and STAT5 mRNA expressions. Supporting findings were obtained from the measurements of tissue CXCL12 mRNA expression and pAkt/Akt, pErk/Erk. Conclusion: In this sophisticated experimental model of OLT, RIC-induced hepatoprotective effects were associated with a downregulation of MIF at mRNA and protein levels, suggesting the role of MIF as a mediator in RIC-induced protection following OLT.

Summary Purpose Enteral and parenteral nutrition of adult critically ill patients varies in terms of the route of nutrient delivery, the amount and composition of macro- and micronutrients, and the choice of specific, immune-modulating substrates. Variations of clinical nutrition may affect clinical outcomes. The present guideline provides clinicians with updated consensus-based recommendations for clinical nutrition in adult critically ill patients who suffer from at least one acute organ dysfunction requiring specific drug therapy and/or a mechanical support device (e.g., mechanical ventilation) to maintain organ function. Methods The former guidelines of the German Society for Nutritional Medicine (DGEM) were updated according to the current instructions of the Association of the Scientific Medical Societies in Germany (AWMF) valid for a S2k-guideline. According to the S2k-guideline classification, no systematic review of the available evidence was required to make recommendations, which, therefore, do not state evidence- or recommendation grades. Nevertheless, we considered and commented the evidence from randomized-controlled trials, meta-analyses and observational studies with adequate sample size and high methodological quality (until May 2018) as well as from currently valid guidelines of other societies. The liability of each recommendation was described linguistically. Each recommendation was finally validated and consented through a Delphi process. Results In the introduction the guideline describes a) the pathophysiological consequences of critical illness possibly affecting metabolism and nutrition of critically ill patients, b) potential definitions for different disease phases during the course of illness, and c) methodological shortcomings of clinical trials on nutrition. Then, we make 69 consented recommendations for essential, practice-relevant elements of clinical nutrition in critically ill patients. Among others, recommendations include the assessment of nutrition status, the indication for clinical nutrition, the timing and route of nutrient delivery, and the amount and composition of substrates (macro- and micronutrients); furthermore, we discuss distinctive aspects of nutrition therapy in obese critically ill patients and those treated with extracorporeal support devices. Conclusion The current guideline provides clinicians with up-to-date recommendations for enteral and parenteral nutrition of adult critically ill patients who suffer from at least one acute organ dysfunction requiring specific drug therapy and/or a mechanical support device (e.g., mechanical ventilation) to maintain organ function. The period of validity of the guideline is approximately fixed at five years (2018–2023).

Perioperative right ventricular (RV) failure due to pressure overload from pulmonary hypertension (PH) worsens postoperative outcomes after cardiac surgery. Inhaled iloprost is a potent pulmonary vasodilator improving RV performance, ameliorating myocardial and pulmonary ischemia-reperfusion injury and attenuating inflammation. We hypothesized that the prophylactic inhalation of iloprost would reduce postoperative ventilation times after cardiac surgery. In this phase III, multicentre, randomized, double-blind, placebo-controlled trial, we randomly assigned 253 cardiac surgical patients at high risk of perioperative RV failure to the prophylactic inhalation of 20 µg iloprost or placebo before and during weaning from extracorporeal circulation. The primary endpoint was the duration of postoperative ventilation. Secondary endpoints included perioperative hemodynamics, intensive care unit and hospital length of stay, and 90-day mortality. Safety was assessed by the incidence of adverse events. Iloprost had no significant effect on the median [interquartile range] duration of postoperative ventilation compared with placebo (720 [470–1170] min vs 778 [541–1219] min, respectively; median decrease, 65 min; 95% confidence interval [CI], − 77 to 210; P = 0.37). While the nebulization of iloprost decreased RV afterload and improved cardiac index, major secondary endpoints were not significantly affected. Ninety-day mortality occurred in 14% of the iloprost patients compared with 14% of the placebo patients (hazard ratio, 0.97; 95% CI, 0.50 to 1.89; P = 0.93). The incidence of adverse events was comparable in both groups. The prophylactic inhalation of iloprost did not meaningfully improve the outcome in high-risk cardiac surgical patients. www.clinicaltrials.gov (NCT00927654); registered 25 June, 2009.

Zusammenfassung Fragestellung Variationen in der klinischen Ernährungstherapie können die Prognose kritisch kranker Patienten beeinflussen. Hier präsentieren wir die Kurzversion der aktualisierten, konsensbasierten S2k-Leitlinie „Klinische Ernährung in der Intensivmedizin“ der Deutschen Gesellschaft für Ernährungsmedizin (DGEM) in Kooperation mit 7 anderen nationalen Fachgesellschaften. Als Zielpopulation der Leitlinie wurden kritisch kranke, erwachsene Patienten, die an mindestens einer akuten, medikamentös und/oder mechanisch unterstützungspflichtigen Organdysfunktion leiden, definiert. Methodik Die früheren Leitlinien der DGEM wurden in Einklang mit den aktuellen Richtlinien der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF) als S2k-Leitlinie aktualisiert. Als Grundlage für die Empfehlungen wurde die Evidenz von randomisiert-kontrollierten Studien, Metaanalysen und Beobachtungsstudien mit angemessener Fallzahl und hoher methodologischer Qualität (bis Mai 2018) sowie aktuell gültige Leitlinien internationaler Fachgesellschaften herangezogen und kommentiert. Die Empfehlungsstärke ist rein sprachlich beschrieben. Jede Empfehlung wurde mittels Delphi-Verfahren abschließend bewertet und konsentiert. Ergebnisse In der vorliegenden Kurzversion werden alle 69 Empfehlungen für essenzielle, praxisrelevante Bestandteile der klinischen Ernährung der Zielpopulation zusammenfassend dargestellt. Ein spezifischer Fokus ist die Adjustierung der Ernährung gemäß den Phasen der kritischen Erkrankung sowie gemäß der individuellen Toleranz gegenüber exogener Substratzufuhr. Unter anderem werden Empfehlungen zur Beurteilung des Ernährungszustandes, zur Indikation für eine klinische Ernährungstherapie, zum Zeitpunkt des Beginns, zum Applikationsweg, zur Menge und Zusammensetzung der Ernährungssubstrate (Makro- und Mikronährstoffe) sowie zu speziellen Aspekten der Ernährung bei adipösen kritisch kranken Patienten und Patienten mit extrakorporalen Unterstützungsverfahren gegeben. Schlussfolgerung Die Kurzversion der Leitlinie gibt eine prägnante Übersicht über alle 69 aktualisierten Handlungsempfehlungen zur enteralen und parenteralen Ernährung erwachsener kritisch kranker Patienten, die an mind. einer akuten, medikamentös und/oder mechanisch unterstützungspflichtigen Organdysfunktion leiden. Die Gültigkeit der Leitlinie beträgt voraussichtlich 5 Jahre (2018 – 2023).

Healthcare : open access journal 9(6), 616 (2021). doi:10.3390/healthcare9060616 special issue: "Special issue "Minimally invasive techniques and advanced surgical procedures" / special issue editor: Dr. Panagiotis Fikatas, guest editor", Published by MDPI, Basel

The urea-creatinine ratio (UCR) has been proposed as potential biomarker for critical illness-associated catabolism. Its role in the context of aneurysmal subarachnoid hemorrhage (aSAH) remains to be elucidated, which was the aim of the present study.We enrolled 66 patients with aSAH with normal renal function and 36 patients undergoing elective cardiac surgery as a control group for the effects of surgery. In patients with aSAH, the predictive or diagnostic value of early (day 0-2) and critical (day 5-7) UCRs was assessed with regard to delayed cerebral ischemia (DCI), DCI-related infarction, and clinical outcome after 12 months.Preoperatively, UCR was similar both groups. Within 2 days postoperatively, UCRs increased significantly in patients in the elective cardiac surgery group (P0.001) but decreased back to baseline on day 5-7 (P = 0.245), whereas UCRs in patients with aSAH increased to significantly greater levels on day 5-7 (P = 0.028). Greater early or critical UCRs were associated with poor clinical outcomes (P = 0.015) or DCI (P = 0.011), DCI-related infarction (P = 0.006), and poor clinical outcomes (P 0.001) respectively. In multivariate analysis, there was an independent association between greater early UCRs and poor clinical outcomes (P = 0.026).In this exploratory study of UCR in the context of aSAH, greater early values were predictive for a poor clinical outcome after 12 months, whereas greater critical values were associated with DCI, DCI-related infarctions, and poor clinical outcomes. The clinical implications as well as the pathophysiologic relevance of protein catabolism should be explored further in the context of aSAH.

Background: Predicting intensive care unit length of stay and outcome following cardiac surgery is currently based on clinical parameters. Novel biomarkers could be employed to improve the prediction models. Methods: We performed a qualitative cytokine screening array to identify highly expressed biomarkers in preoperative blood samples of cardiac surgery patients. After identification of one highly expressed biomarker, growth differentiation factor 15 (GDF-15), a quantitative ELISA was undertaken. Preoperative levels of GDF-15 were compared in regard to duration of intensive care stay, cardio-pulmonary bypass time and indicators of organ dysfunction.Results: Preoperatively, GDF-15 was highly expressed in addition to several less highly expressed other biomarkers. After qualitative analysis we could show that preoperatively raised levels of GDF-15 was positively associated with prolonged ICU stay exceeding 48 h (median 713 versus 1041 pg/ml, p = 0.003). It was also associated with prolonged mechanical ventilation and rates of severe sepsis but not with dialysis rates or cardio-pulmonary bypass time. In univariate regression, raised GDF-15 levels were predictive of a prolonged ICU stay (OR 1.01, 95% Confidence Interval 1 – 1.02, p= 0.029). On ROC curves, GDF-15 was found to predict prolonged ICU stay (AUC= 0.86, 95% Confidence Interval 0.71 – 0.99, p= 0.003).Conclusion: GDF-15 showed potential as predictor of prolonged intensive care stay following cardiac surgery, which might be valuable for risk stratification models.

Mortality in critically ill coronavirus disease 2019 (COVID-19) patients is high and pharmacological treatment strategies remain limited. Early-stage predictive biomarkers are needed to identify patients with a high risk of severe clinical courses and to stratify treatment strategies. Macrophage migration inhibitory factor (MIF) was previously described as a potential predictor for the outcome of critically ill patients and for acute respiratory distress syndrome (ARDS), a hallmark of severe COVID-19 disease. This prospective observational study evaluates the predictive potential of MIF for the clinical outcome after severe COVID-19 infection. Plasma MIF concentrations were measured in 36 mechanically ventilated COVID-19 patients over three days after intensive care unit (ICU) admission. Increased compared to decreased MIF was significantly associated with aggravated organ function and a significantly lower 28-day survival (sequential organ failure assessment (SOFA) score, 8.2 ± 4.5 to 14.3 ± 3, p = 0.009 vs. 8.9 ± 1.9 to 12 ± 2, p = 0.296, survival: 56% vs 93%, p = 0.003). Arterial hypertension was the predominant comorbidity in 85% of patients with increasing MIF concentrations (vs. decreasing MIF: 39%, p = 0.015). Without reaching significance, more patients with decreasing MIF were able to improve their ARDS status (p = 0.142). The identified association between an early MIF response, aggravation of organ function and 28-day survival may open future perspectives for biomarker-based diagnostic approaches for ICU management of COVID-19 patients.

Disease markers 2021, 5564334 (2021). doi:10.1155/2021/5564334, Published by Hindawi, New York, NY [u.a.]

The coronavirus disease 2019 (COVID-19) pandemic has placed a significant burden on hospitals worldwide. Objective biomarkers for early risk stratification and clinical management are still lacking. The aim of this work was to determine whether bioactive adrenomedullin can assist in the risk stratification and clinical management of critically ill COVID-19 patients. Fifty-three patients with confirmed COVID-19 were included in this prospective observational cohort study between March and April 2020. Bioactive adrenomedullin (bio-ADM) plasma concentration was measured daily for seven days after admission. The prognostic value and clinical significance of bio-ADM plasma levels were evaluated for the severity of respiratory failure, the need for extracorporeal organ support and outcome (28-day mortality). Bio-ADM levels increased with the severity of acute respiratory distress syndrome (ARDS, p &lt, 0.001) and were significantly elevated in invasively ventilated patients (p = 0.006) and patients in need of extracorporeal membrane oxygenation (p = 0.040) or renal replacement therapy (RRT, 0.001) compared to patients without these conditions. Non-survivors showed significantly higher bio-ADM levels than survivors (p = 0.010). Bio-ADM levels predicted 28-day mortality (C-index 0.72, 95% confidence interval 0.56–0.87, p &lt, 0.001). Bio-ADM plasma levels correlate with disease severity, the need for extracorporeal organ assistance, and outcome, and highlight the promising value of bio-ADM in the early risk stratification and management of patients with COVID-19.

Introduction Delayed cerebral ischemia (DCI) is a common complication after aneurysmal subarachnoid hemorrhage (aSAH) that can culminate in secondary brain damage. Although it remains one of the main preventable causes of aSAH-related morbidity, there is still a lack of prognostic criteria for identification of patients at risk of developing DCI. Because elevated circulatory levels of the enzyme dipeptidyl peptidase 3 (cDPP3) were recently identified as a potential biomarker for outcome prediction in critically ill patients, we evaluated the time-course of changes in cDPP3 levels after aSAH. Materials and methods cDPP3 levels were quantified in serum obtained from 96 confirmed aSAH patients during the early (EP: d1–4), critical (CP: d5–8, d9–12, d13–15) and late (LP: d16–21) phase after aSAH onset. Associations between cDPP3 levels and demographic or clinical parameters were evaluated. The relations between cDPP3 levels and DCI, DCI-related infarctions and long-term clinical outcomes were examined by receiver operating characteristics (ROC) curve analysis and multivariate logistic regression. Results Significantly higher cDPP3 levels during CP (d5–8, d9–12, d13–15) were observed in patients with poor clinical (p Conclusion Our results provide first evidence that cDPP3 could serve as a promising biomarker for early diagnosis of DCI-related infarctions in poor grade aSAH patients.

Data in Brief 34, 106651 (2021). doi:10.1016/j.dib.2020.106651, Published by Elsevier, Amsterdam [u.a.]

BACKGROUND: Chronic heart failure is one of the most common medical conditions, affecting more than 23 million people worldwide. Despite established guideline‐based, multidrug pharmacotherapy, chronic heart failure is still the cause of frequent hospitalisation, and about 50% die within five years of diagnosis. OBJECTIVES: To assess the effectiveness and safety of ivabradine in individuals with chronic heart failure. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and CPCI‐S Web of Science in March 2020. We also searched ClinicalTrials.gov and the WHO ICTRP. We checked reference lists of included studies. We did not apply any time or language restrictions. SELECTION CRITERIA: We included randomised controlled trials in which adult participants diagnosed with chronic heart failure were randomly assigned to receive either ivabradine or placebo/usual care/no treatment. We distinguished between type of heart failure (heart failure with a reduced ejection fraction or heart failure with a preserved ejection fraction) as well as between duration of ivabradine treatment (short term (< 6 months) or long term (≥ 6 months)). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, extracted data, and checked data for accuracy. We calculated risk ratios (RR) using a random‐effects model. We completed a comprehensive ’Risk of bias’ assessment for all studies. We contacted authors for missing data. Our primary endpoints were: mortality from cardiovascular causes; quality of life; time to first hospitalisation for heart failure during follow‐up; and number of days spent in hospital due to heart failure during follow‐up. Our secondary endpoints were: rate of serious adverse events; exercise capacity; and economic costs (narrative report). We assessed the certainty of the evidence applying the GRADE methodology. MAIN RESULTS: We included 19 studies (76 reports) involving a total of 19,628 participants (mean age 60.76 years, 69% male). However, few studies contributed data to meta‐analyses due to inconsistency in trial design (type of heart failure) and outcome reporting and measurement. In general, risk of bias varied from low to high across the included studies, with insufficient detail provided to inform judgement in several cases. We were able to perform two meta‐analyses focusing on participants with heart failure with a reduced ejection fraction (HFrEF) and long‐term ivabradine treatment. There was evidence of no difference between ivabradine and placebo/usual care/no treatment for mortality from cardiovascular causes (RR 0.99, 95% confidence interval (CI) 0.88 to 1.11; 3 studies; 17,676 participants; I(2) = 33%; moderate‐certainty evidence). Furthermore, we found evidence of no difference in rate of serious adverse events amongst HFrEF participants randomised to receive long‐term ivabradine compared with those randomised to placebo, usual care, or no treatment (RR 0.96, 95% CI 0.92 to 1.00; 2 studies; 17,399 participants; I(2) = 12%; moderate‐certainty evidence). We were not able to perform meta‐analysis for all other outcomes, and have low confidence in the findings based on the individual studies. AUTHORS' CONCLUSIONS: We found evidence of no difference in cardiovascular mortality and serious adverse events between long‐term treatment with ivabradine and placebo/usual care/no treatment in participants with heart failure with HFrEF. Nevertheless, due to indirectness (male predominance), the certainty of the available evidence is rated as moderate.

Hypothermic oxygenated machine perfusion (HOPE) was recently tested in preclinical trials in kidney transplantation (KT). Here we investigate the effects of HOPE on extended-criteria-donation (ECD) kidney allografts (KA). Fifteen ECD-KA were submitted to 152 ± 92 min of end-ischemic HOPE and were compared to a matched group undergoing conventional-cold-storage (CCS) KT (n = 30). Primary (delayed graft function-DGF) and secondary (e.g. postoperative complications, perfusion parameters) endpoints were analyzed within 6-months follow-up. There was no difference in the development of DGF between the HOPE and CCS groups (53% vs. 33%, respectively; p = 0.197). Serum urea was lower following HOPE compared to CCS (p = 0.003), whereas the CCS group displayed lower serum creatinine and higher eGFR rates on postoperative days (POD) 7 and 14. The relative decrease of renal vascular resistance (RR) following HOPE showed a significant inverse association with serum creatinine on POD1 (r = − 0.682; p = 0.006) as well as with serum urea and eGFR. Besides, the relative RR decrease was more prominent in KA with primary function when compared to KA with DGF (p = 0.013). Here we provide clinical evidence on HOPE in ECD-KT after brain death donation. Relative RR may be a useful predictive marker for KA function. Further validation in randomized controlled trials is warranted.Trial registration: clinicaltrials.gov (NCT03378817, Date of first registration: 20/12/2017).

Background: Macrophage Migration Inhibitory Factor (MIF) is highly elevated after cardiac surgery and impacts the postoperative inflammation. The aim of this study was to analyze whether the polymorphisms CATT5&ndash, 7 (rs5844572/rs3063368,&ldquo, 794&rdquo, ) and G&gt, C single-nucleotide polymorphism (rs755622,-173) in the MIF gene promoter are related to postoperative outcome. Methods: In 1116 patients undergoing cardiac surgery, the MIF gene polymorphisms were analyzed and serum MIF was measured by ELISA in 100 patients. Results: Patients with at least one extended repeat allele (CATT7) had a significantly higher risk of acute kidney injury (AKI) compared to others (23% vs. 13%, OR 2.01 (1.40&ndash, 2.88), p = 0.0001). Carriers of CATT7 were also at higher risk of death (1.8% vs. 0.4%, OR 5.12 (0.99&ndash, 33.14), p = 0.026). The GC genotype was associated with AKI (20% vs. GG/CC:13%, OR 1.71 (1.20&ndash, 2.43), p = 0.003). Multivariate analyses identified CATT7 predictive for AKI (OR 2.13 (1.46&ndash, 3.09), p &lt, 0.001) and death (OR 5.58 (1.29&ndash, 24.04), p = 0.021). CATT7 was associated with higher serum MIF before surgery (79.2 vs. 50.4 ng/mL, p = 0.008). Conclusion: The CATT7 allele associates with a higher risk of AKI and death after cardiac surgery, which might be related to chronically elevated serum MIF. Polymorphisms in the MIF gene may constitute a predisposition for postoperative complications and the assessment may improve risk stratification and therapeutic guidance.

The goal of nutrition support is to provide the substrates required to match the bioenergetic needs of the patient and promote the net synthesis of macromolecules required for the preservation of lean mass, organ function, and immunity. Contemporary observational studies have exposed the pervasive undernutrition of critically ill patients and its association with adverse clinical outcomes. The intuitive hypothesis is that optimization of nutrition delivery should improve ICU clinical outcomes. It is therefore surprising that multiple large randomized controlled trials have failed to demonstrate the clinical benefit of restoring or maximizing nutrient intake. This may be in part due to the absence of biological markers that identify patients who are most likely to benefit from nutrition interventions and that monitor the effects of nutrition support. Here, we discuss the need for practical risk stratification tools in critical care nutrition, a proposed rationale for targeted biomarker development, and potential approaches that can be adopted for biomarker identification and validation in the field., SCOPUS: re.j, info:eu-repo/semantics/published

Organoprotective effects of noble gases are subject of current research. One important field of interest is the effect of noble gases on hepatic regenerative capacity. For the noble gas argon, promising studies demonstrated remarkable experimental effects in neuronal and renal cells. The aim of this study was to investigate the effects of argon on the regenerative capacity of the liver after ischemia/reperfusion injury (IRI). Male, Sprague-Dawley rats underwent hepatic IRI by clamping of the hepatic artery. Expression of hepatoproliferative genes (HGF, IL-1&beta, IL-6, TNF), cell cycle markers (BrdU, TUNEL, Ki-67), and liver enzymes (ALT, AST, Bilirubin, LDH) were assessed 3, 36, and 96 h after IRI. Expression of IL-1&beta, and IL-6 was significantly higher after argon inhalation after 36 h (IL-1&beta, 5.0 vs. 8.7 fold, p = 0.001, IL-6 9.6 vs. 19.1 fold, p = 0.05). Ki-67 was higher in the control group compared to the argon group after 36 h (214.0 vs. 38.7 positive cells/1000 hepatocytes, p = 0.045). Serum levels of AST and ALT did not differ significantly between groups. Our data indicate that argon inhalation has detrimental effects on liver regeneration after IRI as measured by elevated levels of the proinflammatory cytokines IL-1&beta, and IL-6 after 36 h. In line with these results, Ki-67 is decreased in the argon group, indicating a negative effect on liver regeneration in argon inhalation.

BACKGROUND: Gastrointestinal (GI) dysfunction is frequent in the critically ill but can be overlooked as a result of the lack of standardization of the diagnostic and therapeutic approaches. We aimed to develop a research agenda for GI dysfunction for future research. We systematically reviewed the current knowledge on a broad range of subtopics from a specific viewpoint of GI dysfunction, highlighting the remaining areas of uncertainty and suggesting future studies. METHODS: This systematic scoping review and research agenda was conducted following successive steps: (1) identify clinically important subtopics within the field of GI function which warrant further research; (2) systematically review the literature for each subtopic using PubMed, CENTRAL and Cochrane Database of Systematic Reviews; (3) summarize evidence for each subtopic; (4) identify areas of uncertainty; (5) formulate and refine study proposals that address these subtopics; and (6) prioritize study proposals via sequential voting rounds. RESULTS: Five major themes were identified: (1) monitoring, (2) associations between GI function and outcome, (3) GI function and nutrition, (4) management of GI dysfunction and (5) pathophysiological mechanisms. Searches on 17 subtopics were performed and evidence summarized. Several areas of uncertainty were identified, six of them needing consensus process. Study proposals ranked among the first ten included: prevention and management of diarrhoea; management of upper and lower feeding intolerance, including indications for post-pyloric feeding and opioid antagonists; acute gastrointestinal injury grading as a bedside tool; the role of intra-abdominal hypertension in the development and monitoring of GI dysfunction and in the development of non-occlusive mesenteric ischaemia; and the effect of proton pump inhibitors on the microbiome in critical illness. CONCLUSIONS: Current evidence on GI dysfunction is scarce, partially due to the lack of precise definitions. The use of core sets of monitoring and outcomes are required to improve the consistency of future studies. We propose several areas for consensus process and outline future study projects., SCOPUS: ar.j, info:eu-repo/semantics/published

Acute kidney injury (AKI) is a relevant complication following thoracoabdominal aortic aneurysm repair (TAAA). Biomarkers, such as secretory leucocyte peptidase inhibitor (SLPI), may enable a more accurate diagnosis. In this study, we tested if SLPI measured in serum is an appropriate biomarker of AKI after TAAA repair. In a prospective observational single-center study including 33 patients (51.5% women, mean age 63.0 ± 16.2 years) undergoing open and endovascular aortic aneurysm repair in 2017, SLPI was measured peri-operatively (until 72 h after surgery). After surgery, the postoperative complications AKI, as defined according to the KDIGO diagnostic criteria, sepsis, death, MACE (major cardiovascular events) and, pneumonia were assessed. In a subgroup analysis, patients with preexisting kidney disease were excluded. Of 33 patients, 51.5% (n = 17) of patients developed AKI. Twelve hours after admission to the intensive care unit (ICU), SLPI serum levels were significantly increased in patients who developed AKI. Multivariable logistic regression revealed a significant association between SLPI 12 hours after admission to ICU and AKI (P = 0.0181, OR = 1.055, 95% CI = 1.009–1.103). The sensitivity of SLPI for AKI prediction was 76.47% (95% CI = 50.1–93.2) and the specificity was 87.5% (95% CI = 61.7–98.4) with an AUC = 0.838 (95% CI = 0.7–0.976) for an optimal cut-off 70.03 ng/ml 12 hours after surgery. In patients without pre-existing impaired renal function, an improved diagnostic quality of SLPI for AKI was observed (Sensitivities of 45.45–91.67%, Specificities of 77.7–100%, AUC = 0.716–0.932). There was no association between perioperative SLPI and the incidence of sepsis, death, MACE (major cardiovascular events), pneumonia. This study suggests that SLPI might be a post-operative biomarker of AKI after TAAA repair, with a superior diagnostic accuracy for patients without preexisting impaired renal function.

Background & Aims Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine and an important regulator of innate immune responses. We hypothesised that serum concentrations of MIF are associated with disease severity and outcome in patients with decompensated cirrhosis and acute-on-chronic liver failure (ACLF). Methods Circulating concentrations of MIF and its soluble receptor CD74 (sCD74) were determined in sera from 292 patients with acute decompensation of cirrhosis defined as new onset or worsening of ascites requiring hospitalisation. Of those, 78 (27%) had ACLF. Short-term mortality was assessed 90 days after inclusion. Results Although serum concentrations of MIF and sCD74 did not correlate with liver function parameters or ACLF, higher MIF (optimum cut-off >2.3 ng/ml) and lower concentrations of sCD74 (optimum cut-off, Graphical abstract, Highlights • MIF serum concentrations do not correlate with hepatic function but with systemic inflammation in decompensated cirrhosis patients. • MIF serum concentrations are independent of genetic MIF promoter polymorphisms in patients with decompensated cirrhosis. • MIF and sCD74 serum concentrations predict transplant-free 90-day survival in patients with decompensated cirrhosis. • Patients with decompensated cirrhosis and both high MIF and low sCD74 serum concentrations have impaired survival. • Patients with decompensated cirrhosis show a transhepatic gradient with higher MIF concentrations in right atrial blood.

Selenoprotein P (SELENOP) is an established biomarker of selenium (Se) status. Serum SELENOP becomes saturated with increasing Se intake, reaching maximal concentrations of 5&ndash, 7 mg SELENOP/L at intakes of ca. 100&ndash, 150 &micro, g Se/d. A biomarker for higher Se intake is missing. We hypothesized that SELENOP may also reflect Se status in clinical applications of therapeutic dosages of selenite. To this end, blood samples from two supplementation studies employing intravenous application of selenite at dosages &gt, 1 mg/d were analyzed. Total Se was quantified by spectroscopy, and SELENOP by a validated ELISA. The high dosage selenite infusions increased SELENOP in parallel to elevated Se concentrations relatively fast to final values partly exceeding 10 mg SELENOP/L. Age or sex were not related to the SELENOP increase. Western blot analyses of SELENOP verified the results obtained by ELISA, and indicated an unchanged pattern of immunoreactive protein isoforms. We conclude that the saturation of SELENOP concentrations observed in prior studies with moderate Se dosages (&lt, 400 &micro, g/d) may reflect an intermediate plateau of expression, rather than an absolute upper limit. Circulating SELENOP seems to be a suitable biomarker for therapeutic applications of selenite exceeding the recommended upper intake levels. Whether SELENOP is also capable of reflecting other supplemental selenocompounds in high dosage therapeutic applications remains to be investigated.

Scientific reports 10, 947 (2020). doi:10.1038/s41598-020-57700-9, Published by Macmillan Publishers Limited, part of Springer Nature, [London]

Nutrients 12(12), 3910 (2020). doi:10.3390/nu12123910, Published by MDPI, Basel

Journal of parenteral and enteral nutrition : JPEN 43(6), 768-779 (2019). doi:10.1002/jpen.1486, Published by Wiley, Hoboken, NJ

Vitamin C, an enzyme cofactor and antioxidant, could hasten the resolution of inflammation, oxidative stress, and microvascular dysfunction. While observational studies have demonstrated that critical illness is associated with low levels of vitamin C, randomized controlled trials (RCTs) of vitamin C, alone or in combination with other antioxidants, have yielded contradicting results. We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials (inception to December 2017) for RCTs comparing vitamin C, by enteral or parenteral routes, with placebo or none, in intensive care unit (ICU) patients. Two independent reviewers assessed study eligibility without language restrictions and abstracted data. Overall mortality was the primary outcome; secondary outcomes were incident infections, ICU length of stay (LOS), hospital LOS, and duration of mechanical ventilation (MV). We prespecified 5 subgroups hypothesized to benefit more from vitamin C. Eleven randomized trials were included. When 9 RCTs (n = 1322) reporting mortality were pooled, vitamin C was not associated with reduced risk of mortality (risk ratio [RR] 0.72, 95% confidence interval [CI]: 0.43-1.20, P = .21). No effect was found on infections, ICU or hospital LOS, or duration of MV. In multiple subgroup comparison, no statistically significant subgroup effects were observed. However, we did observe a tendency towards a mortality reduction (RR 0.21; 95% CI: 0.04-1.05; P = .06) when intravenous high-dose vitamin C monotherapy was administered. Current evidence does not support supplementing critically ill patients with vitamin C. A moderately large treatment effect may exist, but further studies, particularly of monotherapy administration, are warranted.

Extracorporeal life support (ECLS) including venovenous and venoarterial extracorporeal membrane oxygenation (ECMO) and ventricular assist devices (VAD) provide mechanical pulmonary and circulatory support, respectively, in patients with acute pulmonary or cardiovascular failure. This review discusses recently published data regarding specific topics of nutritional support in patients with ECLS and VAD.ECLS may aggravate loss of endogenous and exogenous micronutrients and macronutrients. Observational studies have shown that enteral nutrition is feasible and most commonly used in patients with ECLS. Indirect calorimetry may be feasible for measuring energy expenditure during ECLS. Specific tools are available to assess malnutrition or nutrition risk in patients with VAD but require further validation in the perioperative setting. If parenteral nutrition is indicated, the use of intravenous lipid emulsions may be associated with membrane oxygenator dysfunction of the ECLS device or increased infectious risk in patients with VAD.Despite the exponential use of ECLS and VAD over the last decade, the role of nutrition on clinical outcome in this patient population remains an important but yet underinvestigated field.

Cardiac surgery with cardiopulmonary bypass (CPB) triggers myocardial ischemia/reperfusion injury contributing to organ dysfunction. Preclinical studies revealed that dipeptidyl peptidase (DPP4) inhibition is protective during myocardial infarction. Here, we assessed for the first time the relation of peri-operative DPP4-activity in serum of 46 patients undergoing cardiac surgery with patients’ post-operative organ dysfunction during intensive care unit (ICU) stay. Whereas a prior myocardial infarction significantly reduced pre-operative DDP4-activity, patients with preserved left ventricular function showed an intra-operative decrease of DPP4-activity. The latter correlated with aortic cross clamping time, indicative for the duration of surgery-induced myocardial ischemia. As underlying mechanism, mass-spectrometry revealed increased DPP4 oxidation by cardiac surgery, with DPP4 oxidation reducing DPP4-activity in vitro. Further, post-operative DPP4-activity was negatively correlated with the extent of post-operative organ injury as measured by SAPS II and SOFA scoring, circulating levels of creatinine and lactate, as well as patients’ stay on the ICU. In conclusion, cardiac surgery reduces DPP4-activity through oxidation, with low post-operative DPP4-activity being associated with organ dysfunction and worse outcome of patients during the post-operative ICU stay. This likely reflects the severity of myocardial ischemia/reperfusion injury and may suggest potential beneficial effects of anti-oxidative treatments during cardiac surgery.

Cardiac surgery patients regularly experience a systemic inflammation response to the surgery and a postoperative stay in the intensive care unit. Nutritional support is one strategy to improve the outcome of cardiosurgical patients. A preoperatively diagnosed malnutrition contributes to a higher morbidity and mortality in this patient group. Preoperative fasting, glucose-free infusions during long and invasive operations and delayed postoperative nutrition therapy aggravate the nutrition situation. However, conclusive evidence for this population, consisting of well-conducted clinical trials is lacking.This article outlines the main causes for malnutrition in cardiosurgical patients and summarizes possibilities to identify patients at high nutritional risk, who are most likely to profit from aggressive nutritional therapy. Despite conspicuous knowledge and evidence gaps, a rational nutritional support therapy based on current recommendations of ASPEN, ESPEN and an international multidisciplinary consensus group is presented. The amount and kind of nutrition, as well as the best time to initiate nutrition support, ways to monitor nutrition therapy and the potential use of pharmaconutrition to modulate the inflammatory response to cardiopulmonary bypass are presented to benefit patients undergoing cardiac surgery.

Objectives: Haemolysis during left ventricular assist device support is associated with thrombosis. In this retrospective study, we analysed whether low-level haemolysis (LLH) as defined by simultaneously elevated lactate dehydrogenase (LDH) and free haemoglobin (fHb) levels had an impact on thromboembolic and bleeding events and on von Willebrand factor levels in HeartMate II patients. Methods: After exclusion of patients with LDH >700 U/l and fHb >40 mg/dl at hospital discharge, 79 HeartMate II patients were included. LDH and fHb levels were measured at discharge and in 3 months interval. von Willebrand factor activity and antigen activity were measured 3 months postoperatively. Outcomes regarding ischaemic stroke (IS), pump thrombosis (PT) and gastrointestinal bleeding were recorded. Patients with LLH (400

BACKGROUND In long-term left ventricular assist device (LVAD) therapy, recurrent bleeding events may justify cessation of anticoagulation therapy (AT). However, data about THE safety and risks of AT cessation in LVAD patients are scarce.Methods and Results:Between 2010 and 2015, 128 patients received a HeartMate II (HMII). Following recurrent bleeding events, we ceased vitamin K antagonist (VKA) therapy in 13 patients (10%) (no-VKA group). To characterize the hemostatic profile, we performed von Willebrand factor (vWF), platelet function (PF), and other hemostatic tests in all HMII patients. The incidence of pump thrombosis (PT), ischemic stroke (IS) and bleeding events in this HMII population was 4.7 %, 6.2% and 36.7%, respectively. Median survival without VKA was 435 days. No cases of PT and only 1 of IS occurred after AT discontinuation. All patients had impaired PF and acquired von Willebrand syndrome (AvWS). However, the vWF collagen-binding activity to antigen ratio before and after VKA cessation was significantly lower in the no-VKA group compared with the HMII population (0.60±0.12 vs. 0.73±0.14, P=0.006). The thrombin-antithrombin III complex (TAT) value was significantly higher in the no-VKA group (P=0.0005). CONCLUSIONS We experienced good results with AT cessation in specific HMII patients. The simultaneous onset of AvWS and high TAT values could explain at least in part the low thromboembolic rate in HMII patients without VKA.

Annals of thoracic and cardiovascular surgery 24(5), 230-237 (2018). doi:10.5761/atcs.oa.18-00019, Published by Medical Tribune, Tokyo

SCOPUS: re.j, info:eu-repo/semantics/published