Publications by authors named "Marcel C G van de Poll"

51 Publications

Ingestion of Free Amino Acids Compared with an Equivalent Amount of Intact Protein Results in More Rapid Amino Acid Absorption and Greater Postprandial Plasma Amino Acid Availability Without Affecting Muscle Protein Synthesis Rates in Young Adults in a Double-Blind Randomized Trial.

J Nutr 2021 Oct 12. Epub 2021 Oct 12.

Department of Human Biology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre+, Maastricht, The Netherlands.

Background: The rate of protein digestion and amino acid absorption determines the postprandial rise in circulating amino acids and modulates postprandial muscle protein synthesis rates.

Objective: We sought to compare protein digestion, amino acid absorption kinetics, and the postprandial muscle protein synthetic response following ingestion of intact milk protein or an equivalent amount of free amino acids.

Methods: Twenty-four healthy, young participants (mean ± SD age: 22 ± 3 y and BMI 23 ± 2 kg/m2; sex: 12 male and 12 female participants) received a primed continuous infusion of l-[ring-2H5]-phenylalanine and l-[ring-3,5-2H2]-tyrosine, after which they ingested either 30 g intrinsically l-[1-13C]-phenylalanine-labeled milk protein or an equivalent amount of free amino acids labeled with l-[1-13C]-phenylalanine. Blood samples and muscle biopsies were obtained to assess protein digestion and amino acid absorption kinetics (secondary outcome), whole-body protein net balance (secondary outcome), and mixed muscle protein synthesis rates (primary outcome) throughout the 6-h postprandial period.

Results: Postprandial plasma amino acid concentrations increased after ingestion of intact milk protein and free amino acids (both P < 0.001), with a greater increase following ingestion of the free amino acids than following ingestion of intact milk protein (P-time × treatment < 0.001). Exogenous phenylalanine release into plasma, assessed over the 6-h postprandial period, was greater with free amino acid ingestion (76 ± 9%) than with milk protein treatment (59 ± 10%; P < 0.001). Ingestion of free amino acids and intact milk protein increased mixed muscle protein synthesis rates (P-time < 0.001), with no differences between treatments (from 0.037 ± 0.015%/h to 0.053 ± 0.014%/h and 0.039 ± 0.016%/h to 0.051 ± 0.010%/h, respectively; P-time × treatment = 0.629).

Conclusions: Ingestion of a bolus of free amino acids leads to more rapid amino acid absorption and greater postprandial plasma amino acid availability than ingestion of an equivalent amount of intact milk protein. Ingestion of free amino acids may be preferred over ingestion of intact protein in conditions where protein digestion and amino acid absorption are compromised.
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http://dx.doi.org/10.1093/jn/nxab305DOI Listing
October 2021

Differences and Similarities Among Coronavirus Disease 2019 Patients Treated in Seven ICUs in Three Countries Within One Region: An Observational Cohort Study.

Crit Care Med 2021 Oct 12. Epub 2021 Oct 12.

Department of Intensive Care, Ziekenhuis Oost-Limburg, Genk, Belgium. UHasselt, Faculty of Medicine and Life Sciences, Diepenbeek, Belgium. Department of Intensive Care, Maastricht University Medical Center +, Maastricht, The Netherlands. Department of Intensive Care, Laurentius Ziekenhuis, Roermond, The Netherlands. Care and Public Health Research Institute, Maastricht University, Maastricht, The Netherlands. Department of Intensive Care, Jessa Hospital, Hasselt, Belgium. Department of Intensive Care, VieCuri Medisch Centrum, Venlo, The Netherlands. Department of Intensive Care, Zuyderland Medisch Centrum, Heerlen/Sittard, The Netherlands. Department of Surgery, Maastricht University Medical Center +, Maastricht, The Netherlands. School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands. Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands. Division for Acute and Emergency Medicine, Maastricht University Medical Center +, Maastricht, The Netherlands. Department of Intensive Care, University Hospital Rheinisch Westfälische Hochschule Aachen, Aachen, Germany.

Objectives: To investigate healthcare system-driven variation in general characteristics, interventions, and outcomes in coronavirus disease 2019 (COVID-19) patients admitted to the ICU within one Western European region across three countries.

Design: Multicenter observational cohort study.

Setting: Seven ICUs in the Euregio Meuse-Rhine, one region across Belgium, The Netherlands, and Germany.

Patients: Consecutive COVID-19 patients supported in the ICU during the first pandemic wave.

Interventions: None.

Measurements And Main Results: Baseline demographic and clinical characteristics, laboratory values, and outcome data were retrieved after ethical approval and data-sharing agreements. Descriptive statistics were performed to investigate country-related practice variation. From March 2, 2020, to August 12, 2020, 551 patients were admitted. Mean age was 65.4 ± 11.2 years, and 29% were female. At admission, Acute Physiology and Chronic Health Evaluation II scores were 15.0 ± 5.5, 16.8 ± 5.5, and 15.8 ± 5.3 (p = 0.002), and Sequential Organ Failure Assessment scores were 4.4 ± 2.7, 7.4 ± 2.2, and 7.7 ± 3.2 (p < 0.001) in the Belgian, Dutch, and German parts of Euregio, respectively. The ICU mortality rate was 22%, 42%, and 44%, respectively (p < 0.001). Large differences were observed in the frequency of organ support, antimicrobial/inflammatory therapy application, and ICU capacity. Mixed-multivariable logistic regression analyses showed that differences in ICU mortality were independent of age, sex, disease severity, comorbidities, support strategies, therapies, and complications.

Conclusions: COVID-19 patients admitted to ICUs within one region, the Euregio Meuse-Rhine, differed significantly in general characteristics, applied interventions, and outcomes despite presumed genetic and socioeconomic background, admission diagnosis, access to international literature, and data collection are similar. Variances in healthcare systems' organization, particularly ICU capacity and admission criteria, combined with a rapidly spreading pandemic might be important drivers for the observed differences. Heterogeneity between patient groups but also healthcare systems should be presumed to interfere with outcomes in coronavirus disease 2019.
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http://dx.doi.org/10.1097/CCM.0000000000005314DOI Listing
October 2021

Ethics of ECPR research.

Resuscitation 2021 Aug 17. Epub 2021 Aug 17.

Department of Cardiothoracic Surgery, Maastricht University Medical Centre, Maastricht, the Netherlands.

The design of emergency medicine trials can raise several ethical concerns - risks may be greater, and randomisation may have to occur before consent. Research in emergency medicine is thus an illuminating context to explore the interplay between risk and randomisation, and the consequences for consent. Using a currently running trial, we describe possible concerns, considerations, and solutions to reconcile the conflicting interests of scientific inquiry, ethical principles, and clinical reality in emergency medicine research.
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http://dx.doi.org/10.1016/j.resuscitation.2021.08.007DOI Listing
August 2021

Systemic inflammation down-regulates glyoxalase-1 expression: an experimental study in healthy males.

Biosci Rep 2021 Jul;41(7)

Department of Intensive Care Medicine, Maastricht University Medical Center +, Maastricht, The Netherlands.

Background: Hypoxia and inflammation are hallmarks of critical illness, related to multiple organ failure. A possible mechanism leading to multiple organ failure is hypoxia- or inflammation-induced down-regulation of the detoxifying glyoxalase system that clears dicarbonyl stress. The dicarbonyl methylglyoxal (MGO) is a highly reactive agent produced by metabolic pathways such as anaerobic glycolysis and gluconeogenesis. MGO leads to protein damage and ultimately multi-organ failure. Whether detoxification of MGO into D-lactate by glyoxalase functions appropriately under conditions of hypoxia and inflammation is largely unknown. We investigated the effect of inflammation and hypoxia on the MGO pathway in humans in vivo.

Methods: After prehydration with glucose 2.5% solution, ten healthy males were exposed to hypoxia (arterial saturation 80-85%) for 3.5 h using an air-tight respiratory helmet, ten males to experimental endotoxemia (LPS 2 ng/kg i.v.), ten males to LPS+hypoxia and ten males to none of these interventions (control group). Serial blood samples were drawn, and glyoxalase-1 mRNA expression, MGO, methylglyoxal-derived hydroimidazolone-1 (MG-H1), D-lactate and L-lactate levels, were measured serially.

Results: Glyoxalase-1 mRNA expression decreased in the LPS (β (95%CI); -0.87 (-1.24; -0.50) and the LPS+hypoxia groups; -0.78 (-1.07; -0.48) (P<0.001). MGO was equal between groups, whereas MG-H1 increased over time in the control group only (P=0.003). D-Lactate was increased in all four groups. L-Lactate was increased in all groups, except in the control group.

Conclusion: Systemic inflammation downregulates glyoxalase-1 mRNA expression in humans. This is a possible mechanism leading to cell damage and multi-organ failure in critical illness with potential for intervention.
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http://dx.doi.org/10.1042/BSR20210954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411911PMC
July 2021

Functional Outcomes and Their Association With Physical Performance in Mechanically Ventilated Coronavirus Disease 2019 Survivors at 3 Months Following Hospital Discharge: A Cohort Study.

Crit Care Med 2021 10;49(10):1726-1738

Department of Intensive Care Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands.

Objectives: We performed a comprehensive health assessment in mechanically ventilated coronavirus disease 2019 survivors to assess the impact of respiratory and skeletal muscle injury sustained during ICU stay on physical performance at 3 months following hospital discharge.

Design: Preregistered prospective observational cohort study.

Setting: University hospital ICU.

Patients: All mechanically ventilated coronavirus disease 2019 patients admitted to our ICU during the first European pandemic wave.

Measurements And Main Results: At 3 months after hospital discharge, 46 survivors underwent a comprehensive physical assessment (6-min walking distance, Medical Research Council sum score and handgrip strength), a full pulmonary function test, and a chest CT scan which was used to analyze skeletal muscle architecture. In addition, patient-reported outcomes measures were collected. Physical performance assessed by 6-minute walking distance was below 80% of predicted in 48% of patients. Patients with impaired physical performance had more muscle weakness (Medical Research Council sum score 53 [51-56] vs 59 [56-60]; p < 0.001), lower lung diffusing capacity (54% [44-66%] vs 68% of predicted [61-72% of predicted]; p = 0.002), and higher intermuscular adipose tissue area (p = 0.037). Reduced lung diffusing capacity and increased intermuscular adipose tissue were independently associated with physical performance.

Conclusions: Physical disability is common at 3 months in severe coronavirus disease 2019 survivors. Lung diffusing capacity and intermuscular adipose tissue assessed on CT were independently associated with walking distance, suggesting a key role for pulmonary function and muscle quality in functional disability.
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http://dx.doi.org/10.1097/CCM.0000000000005089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439632PMC
October 2021

Edema in critically ill patients leads to overestimation of skeletal muscle mass measurements using computed tomography scans.

Nutrition 2021 09 7;89:111238. Epub 2021 Mar 7.

Department of Intensive Care Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands; School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands; Department of Surgery, Maastricht University Medical Centre, Maastricht, the Netherlands.

Objectives: Changes in muscle mass and quality are important targets for nutritional intervention in critical illness. Effects of such interventions may be assessed using sequential computed tomography (CT) scans. However, fluid and lipid infiltration potentially affects muscle area measurements. The aim of this study was to evaluate changes in muscle mass and quality in critical illness with special emphasis on the influence of edema on this assessment.

Methods: Changes in skeletal muscle area index (SMI) and radiation attenuation (RA) at the level of vertebra L3 were analyzed using sequential CT scans of 77 patients with abdominal sepsis. Additionally, the relation between these changes and disease severity using the maximum Sequential Organ Failure Assessment (SOFA) score and change in edema were studied.

Results: SMI declined on average 0.35%/d (±1.22%; P = 0.013). However, SMI increased in 41.6% of the study population. Increasing edema formation was significantly associated with increased SMI and with a higher SOFA score. Muscle RA decreased during critical illness, but was not significantly associated with changes in SMI or changes in edema.

Conclusion: In critically ill patients, edema affects skeletal muscle area measurements, which leads to an overestimation of skeletal muscle area. A higher SOFA score was associated with edema formation. Because both edema and fat infiltration may affect muscle RA, the separate effects of these on muscle quality are difficult to distinguish. When using abdominal CT scans to changes in muscle mass and quality in critically ill patients, researchers must be aware and careful with the interpretation of the results.
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http://dx.doi.org/10.1016/j.nut.2021.111238DOI Listing
September 2021

Postprandial rise of essential amino acids is impaired during critical illness and unrelated to small-intestinal function.

JPEN J Parenter Enteral Nutr 2021 Mar 5. Epub 2021 Mar 5.

Department of Surgery, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.

Background: Postprandial rise of plasma essential amino acids (EAAs) determines the anabolic effect of dietary protein. Disturbed gastrointestinal function could impair the anabolic response in critically ill patients. Aim was to investigate the postprandial EAA response in critically ill patients and its relation to small-intestinal function.

Methods: Twenty-one mechanically ventilated patients and 9 healthy controls received a bolus containing 100 ml of a formula feed (Ensure) and 2 g of 3-O-Methyl-d-glucose (3-OMG) via postpyloric feeding tube. Fasting and postprandial plasma concentrations of EAAs, 3-OMG, total bile salts, and the gut-released hormone fibroblast growth factor 19 (FGF19) were measured over a 4-hour period. Changes over time and between groups were assessed with linear mixed-effects analysis. Early (0-60 minutes) and total postprandial responses are summarized as the incremental area under the curve (iAUC).

Results: At baseline, fasting EAA levels were similar in both groups: 1181 (1055-1276) vs 1150 (1065-1334) μmol·L-1, P = .87. The early postprandial rise in EAA was not apparent in critically ill patients compared with healthy controls (iAUC , -4858 [-6859 to 2886] vs 5406 [3099-16,853] µmol·L ·60 minutes; P = .039). Impaired EAA response did not correlate with impaired 3-OMG response (Spearman ρ 0.32, P = .09). There was a limited increase in total bile salts but no relevant FGF19 response in either group.

Conclusion: Postprandial rise of EAA is blunted in critically ill patients and unrelated to glucose absorption measured with 3-OMG. Future studies should aim to delineate governing mechanisms of macronutrient malabsorption.
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http://dx.doi.org/10.1002/jpen.2103DOI Listing
March 2021

Decreased serial scores of severe organ failure assessments are associated with survival in mechanically ventilated patients; the prospective Maastricht Intensive Care COVID cohort.

J Crit Care 2021 04 17;62:38-45. Epub 2020 Nov 17.

Department of Intensive Care, Maastricht University Medical Centre+, P. Debyelaan 25, 6202 AZ Maastricht, the Netherlands; Care and Public Health Research Institute (CAPHRI), Maastricht University, Universiteitssingel 40, 6229 ER Maastricht, the Netherlands. Electronic address:

Background: The majority of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are admitted to the Intensive Care Unit (ICU) for mechanical ventilation. The role of multi-organ failure during ICU admission as driver for outcome remains to be investigated yet.

Design And Setting: Prospective cohort of mechanically ventilated critically ill with SARS-CoV-2 infection.

Participants And Methods: 94 participants of the MaastrICCht cohort (21% women) had a median length of stay of 16 days (maximum of 77). After division into survivors (n = 59) and non-survivors (n = 35), we analysed 1555 serial SOFA scores using linear mixed-effects models.

Results: Survivors improved one SOFA score point more per 5 days (95% CI: 4-8) than non-survivors. Adjustment for age, sex, and chronic lung, renal and liver disease, body-mass index, diabetes mellitus, cardiovascular risk factors, and Acute Physiology and Chronic Health Evaluation II score did not change this result. This association was stronger for women than men (P-interaction = 0.043).

Conclusions: The decrease in SOFA score associated with survival suggests multi-organ failure involvement during mechanical ventilation in patients with SARS-CoV-2. Surviving women appeared to improve faster than surviving men. Serial SOFA scores may unravel an unfavourable trajectory and guide decisions in mechanically ventilated patients with SARS-CoV-2.
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http://dx.doi.org/10.1016/j.jcrc.2020.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669472PMC
April 2021

Anti-C5a antibody IFX-1 (vilobelimab) treatment versus best supportive care for patients with severe COVID-19 (PANAMO): an exploratory, open-label, phase 2 randomised controlled trial.

Lancet Rheumatol 2020 Dec 28;2(12):e764-e773. Epub 2020 Sep 28.

Department of Neurology, Amsterdam Neuroscience, University of Amsterdam, Amsterdam UMC, Amsterdam, Netherlands.

Background: Severe COVID-19 is characterised by inflammation and coagulation in the presence of complement system activation. We aimed to explore the potential benefit and safety of selectively blocking the anaphylatoxin and complement protein C5a with the monoclonal antibody IFX-1 (vilobelimab), in patients with severe COVID-19.

Methods: We did an exploratory, open-label, randomised phase 2 trial (part of the adaptive phase 2/3 PANAMO trial) of intravenous IFX-1 in adults with severe COVID-19 at three academic hospitals in the Netherlands. Eligibility criteria were age 18 years or older; severe pneumonia with pulmonary infiltrates consistent with pneumonia, a clinical history of severe shortness of breath within the past 14 days, or a need for non-invasive or invasive ventilation; severe disease defined as a ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air (PaO/FiO) between 100 mm Hg and 250 mm Hg in the supine position; and severe acute respiratory syndrome coronavirus 2 infection confirmed by RT-PCR. Patients were randomly assigned 1:1 to receive IFX-1 (up to seven doses of 800 mg intravenously) plus best supportive care (IFX-1 group) or best supportive care only (control group). The primary outcome was the percentage change in PaO/FiO in the supine position between baseline and day 5. Mortality at 28 days and treatment-emergent and serious adverse events were key secondary outcomes. The primary analysis was done in the intention-to-treat population and safety analyses were done in all patients according to treatment received. This trial is registered at ClinicalTrials.gov (NCT04333420).

Findings: Between March 31 and April 24, 2020, 30 patients were enrolled and randomly assigned to the IFX-1 group (n=15) or the control group (n=15). During the study it became clear that several patients could not be assessed regularly in the supine position because of severe hypoxaemia. It was therefore decided to focus on all PaO/FiO assessments (irrespective of position). At day 5 after randomisation, the mean PaO/FiO (irrespective of position) was 158 mm Hg (SD 63; range 84-265) in the IFX-1 group and 189 mm Hg (89; 71-329) in the control group. Analyses of the least squares mean relative change in PaO/FiO at day 5 showed no differences between treatment groups (17% change in the IFX-1 group 41% in the control group; difference -24% [95% CI -58 to 9], p=0·15. Kaplan-Meier estimates of mortality by 28 days were 13% (95% CI 0-31) for the IFX-1 group and 27% (4-49) for the control group (adjusted hazard ratio for death 0·65 [95% CI 0·10-4·14]). The frequency of serious adverse events were similar between groups (nine [60%] in the IFX-1 group seven [47%] in the control group) and no deaths were considered related to treatment assignment. However, a smaller proportion of patients had pulmonary embolisms classed as serious in the IFX-1 group (two [13%]) than in the control group (six [40%]). Infections classed as serious were reported in three (20%) patients in the IFX-1 group versus five (33%) patients in the control group.

Interpretation: In this small exploratory phase 2 part of the PANAMO trial, C5a inhibition with IFX-1 appears to be safe in patients with severe COVID-19. The secondary outcome results in favour of IFX-1 are preliminary because the study was not powered on these endpoints, but they support the investigation of C5a inhibition with IFX-1 in a phase 3 trial using 28-day mortality as the primary endpoint.

Funding: InflaRx.
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http://dx.doi.org/10.1016/S2665-9913(20)30341-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521913PMC
December 2020

Serial measurements in COVID-19-induced acute respiratory disease to unravel heterogeneity of the disease course: design of the Maastricht Intensive Care COVID cohort (MaastrICCht).

BMJ Open 2020 09 29;10(9):e040175. Epub 2020 Sep 29.

Department of Intensive Care, Maastricht University Medical Center+, Maastricht, The Netherlands.

Introduction: The course of the disease in SARS-CoV-2 infection in mechanically ventilated patients is unknown. To unravel the clinical heterogeneity of the SARS-CoV-2 infection in these patients, we designed the prospective observational Maastricht Intensive Care COVID cohort (MaastrICCht). We incorporated serial measurements that harbour aetiological, diagnostic and predictive information. The study aims to investigate the heterogeneity of the natural course of critically ill patients with a SARS-CoV-2 infection.

Methods And Analysis: Mechanically ventilated patients admitted to the intensive care with a SARS-CoV-2 infection will be included. We will collect clinical variables, vital parameters, laboratory variables, mechanical ventilator settings, chest electrical impedance tomography, ECGs, echocardiography as well as other imaging modalities to assess heterogeneity of the course of a SARS-CoV-2 infection in critically ill patients. The MaastrICCht is also designed to foster various other studies and registries and intends to create an open-source database for investigators. Therefore, a major part of the data collection is aligned with an existing national intensive care data registry and two international COVID-19 data collection initiatives. Additionally, we create a flexible design, so that additional measures can be added during the ongoing study based on new knowledge obtained from the rapidly growing body of evidence. The spread of the COVID-19 pandemic requires the swift implementation of observational research to unravel heterogeneity of the natural course of the disease of SARS-CoV-2 infection in mechanically ventilated patients. Our study design is expected to enhance aetiological, diagnostic and prognostic understanding of the disease. This paper describes the design of the MaastrICCht.

Ethics And Dissemination: Ethical approval has been obtained from the medical ethics committee (Medisch Ethische Toetsingscommissie 2020-1565/3 00 523) of the Maastricht University Medical Centre+ (Maastricht UMC+), which will be performed based on the Declaration of Helsinki. During the pandemic, the board of directors of Maastricht UMC+ adopted a policy to inform patients and ask their consent to use the collected data and to store serum samples for COVID-19 research purposes. All study documentation will be stored securely for fifteen years after recruitment of the last patient. The results will be published in peer-reviewed academic journals, with a preference for open access journals, while particularly considering deposition of the manuscripts on a preprint server early.

Trial Registration Number: The Netherlands Trial Register (NL8613).
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http://dx.doi.org/10.1136/bmjopen-2020-040175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526030PMC
September 2020

Early ICU-mortality in sepsis - causes, influencing factors and variability in clinical judgement: a retrospective cohort study.

Infect Dis (Lond) 2021 Jan 15;53(1):61-68. Epub 2020 Sep 15.

Department of Intensive Care Medicine, Maastricht University Medical Center +, Maastricht, The Netherlands.

Background: Sepsis is a global health care problem with a high mortality. Early death seems common; however, data are sparse. The objective of the present study was to report causes and influencing factors of early death in sepsis and septic shock.

Methods: All septic ICU patients were included from 2012 to 2017. Early death was predefined as occurring within 48 h. Causes and factors leading up to death were reported by a panel of four intensivists, independently reviewing the medical files. Following factors were assessed: (1) delay in ICU admission; (2) futile ICU treatment; (3) missed diagnosis or inadequate treatment on the ICU. Fleiss kappa was used to assess inter-observer agreement.

Results: 1107 septic patients (APACHE II score 25 ± 8) were included. 344 patients died of which 97 (28%) within 48 h. In 33% an autopsy was performed. Primary causes of early death were multiple organ failure, mesenteric ischaemia and death after cardio-pulmonary resuscitation (CPR). Delay in ICU admission was scored in 32% of early deaths with slight agreement (κ = 0.180), futile ICU treatment in 29% with moderate agreement (κ = 0.415) and missed diagnosis or treatment in 7% of cases with slight agreement (κ = 0.122).

Conclusions: Early death after ICU admission in sepsis is common and primarily caused by multiple organ failure, mesenteric ischaemia and death after unsuccessful CPR. Influencing factors were delay in ICU admission and futile ICU admission. Fleiss kappa indicates substantial variability in clinical judgement between intensivists, strengthening the necessity for shared decision making.
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http://dx.doi.org/10.1080/23744235.2020.1821912DOI Listing
January 2021

Preoperative Risk Assessment: A Poor Predictor of Outcome in Critically ill Elderly with Sepsis After Abdominal Surgery.

World J Surg 2020 Dec 30;44(12):4060-4069. Epub 2020 Aug 30.

Department of Surgery, Maastricht University Medical Centre+, Postbus 5800, 6202 AZ, Maastricht, The Netherlands.

Background: Postoperative outcome prediction in elderly is based on preoperative physical status but its predictive value is uncertain. The goal was to evaluate the value of risk assessment performed perioperatively in predicting outcome in case of admission to an intensive care unit (ICU).

Methods: A total of 108 postsurgical patients were retrospectively selected from a prospectively recorded database of 144 elderly septic patients (>70 years) admitted to the ICU department after elective or emergency abdominal surgery between 2012 and 2017. Perioperative risk assessment scores including Portsmouth Physiological and Operative Severity Score for the enumeration of Mortality (P-POSSUM) and American Society of Anaesthesiologists Physical Status classification (ASA) were determined. Acute Physiology and Chronic Health Evaluation IV (APACHE IV) was obtained at ICU admission.

Results: In-hospital mortality was 48.9% in elderly requiring ICU admission after elective surgery (n = 45), compared to 49.2% after emergency surgery (n = 63). APACHE IV significantly predicted in-hospital mortality after complicated elective surgery [area under the curve 0.935 (p < 0.001)] where outpatient ASA physical status and P-POSSUM did not. In contrast, P-POSSUM and APACHE IV significantly predicted in-hospital mortality when based on current physical state in elderly requiring emergency surgery (AUC 0.769 (p = 0.002) and 0.736 (p = 0.006), respectively).

Conclusions: Perioperative risk assessment reflecting premorbid physical status of elderly loses its value when complications occur requiring unplanned ICU admission. Risks in elderly should be re-assessed based on current clinical condition prior to ICU admission, because outcome prediction is more reliable then.
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http://dx.doi.org/10.1007/s00268-020-05742-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599195PMC
December 2020

Diarrhea and elevation of plasma markers of cholestasis are common and often occur concomitantly in critically ill patients.

J Crit Care 2020 12 8;60:120-126. Epub 2020 Aug 8.

Department of Anaesthesiology and Intensive Care, University of Tartu, Tartu, Estonia; Department of Intensive Care Medicine, Lucerne Cantonal Hospital, Lucerne, Switzerland. Electronic address:

Purpose: We aimed to describe epidemiology of diarrhea and cholestasis in critically ill patients and explore associations between these two conditions.

Material And Methods: We performed a retrospective study including all consecutive patients who stayed in the ICU for at least 3 days and in whom plasma measurements of liver enzymes/cholestasis parameters were performed. Diarrhea was defined as 3 or more loose or liquid stools per day and cholestasis as increase of alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GGT) 1.5 times above the upper limit of normality.

Results: Diarrhea was observed in 26.1% and cholestasis in 27.9% of study patients, about one third of the cases in both diarrhea and cholestasis occurred beyond the first week of patient's ICU stay. Cholestasis occurred in 45.6% of patients with diarrhea vs 28.0% of patients without diarrhea (p < 0.001). In 94 patients (13.1%) both diarrhea and cholestasis occurred, cholestasis was more commonly (2/3 of cases) documented before manifestation of diarrhea.

Conclusions: Cholestasis is more common in patients with diarrhea and vice versa. Diarrhea and cholestasis both occur in approximately one quarter of ICU patients, with significant proportion manifesting beyond the first week in the ICU.
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http://dx.doi.org/10.1016/j.jcrc.2020.08.004DOI Listing
December 2020

Whole Body CT Imaging in Deceased Donor Screening for Malignancies.

Transplant Direct 2019 Dec 15;5(12):e509. Epub 2019 Nov 15.

Department of Surgery, Division of Transplantation, Leiden University Medical Center, Leiden University, Leiden, The Netherlands.

Background: In most western countries, the median donor age is increasing. The incidence of malignancies in older populations is increasing as well. To prevent donor-derived malignancies we evaluated radiologic donor screening in a retrospective donor cohort.

Methods: This study analyzes the efficacy of a preoperative computed tomography (CT) scan on detecting malignancies. All deceased organ donors in the Netherlands between January 2013 and December 2017 were included. Donor reports were analyzed to identify malignancies detected before or during organ procurement. Findings between donor screening with or without CT-scan were compared.

Results: Chest or abdominal CT-scans were performed in 17% and 18% of the 1644 reported donors respectively. Screening by chest CT-scan versus radiograph resulted in 1.5% and 0.0% detected thoracic malignancies respectively. During procurement no thoracic malignancies were found in patients screened by chest CT compared with 0.2% malignancies in the radiograph group. Screening by abdominal CT-scan resulted in 0.0% malignancies, compared with 0.2% in the abdominal ultrasound group. During procurement 1.0% and 1.3% malignancies were found in the abdominal CT-scan and ultrasound groups, respectively.

Conclusions: Screening by CT-scan decreased the perioperative detection of tumors by 30%. A preoperative CT-scan may be helpful by providing additional information on (aberrant) anatomy to the procuring or transplanting surgeon. In conclusion, donor screening by CT-scan could decrease the risk of donor-derived malignancies and prevents unnecessary procurements per year in the Netherlands.
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http://dx.doi.org/10.1097/TXD.0000000000000953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004587PMC
December 2019

Metabolic aspects of muscle wasting during critical illness.

Curr Opin Clin Nutr Metab Care 2020 03;23(2):96-101

Department of Intensive Care Medicine.

Purpose Of Review: Skeletal muscle wasting during critical illness is the result of disturbed metabolism. No proven effective interventions targeting skeletal muscle mass and function during critical illness currently exist. This review summarizes recent advances regarding the complexity of metabolic factors involved and the challenge of establishing the clinical effects of metabolic interventions targeting the muscle.

Recent Findings: Although the catabolic state is limited to the acute phase of critical illness, its subsequent impact on muscle mass and function persists long after ICU discharge. Immobilization, inflammation and disturbed muscle energy and nutrient metabolism are key drivers of muscle protein loss. Current research focuses on the effects of enhanced protein provision, specific substrate delivery and physical exercise. Whilst some interventions have been successful at improving muscle mass, these effects do not always carry over into muscle function or strength.

Summary: Increased understanding of metabolic derangements during critical illness provides new potential targets for treatment. The potential of dietary protein to attenuate the muscle protein catabolic state has yet to be established in clinical trials. Basic research should focus on ways to further improve the anabolic potential of nutrition by unravelling mechanisms that regulate anabolic and catabolic pathways and energy metabolism.
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http://dx.doi.org/10.1097/MCO.0000000000000628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015189PMC
March 2020

Muscle wasting associated co-morbidities, rather than sarcopenia are risk factors for hospital mortality in critical illness.

J Crit Care 2020 04 26;56:31-36. Epub 2019 Nov 26.

Department of Intensive Care Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands; School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands; Department of Surgery, Maastricht University Medical Centre, Maastricht, the Netherlands.

Background: Low skeletal muscle mass on intensive care unit admission is related to increased mortality. It is however unknown whether this association is influenced by co-morbidities that are associated with skeletal muscle loss. The aim of this study was to investigate whether sarcopenia is an independent risk factor for hospital mortality in critical illness in the presence of co-morbidities associated with muscle wasting.

Methods: Data of 155 patients with abdominal sepsis were retrospectively analyzed. Skeletal muscle area was assessed using CT-scans at the level of vertebra L3. Demographic and clinical data were retrieved from electronic patient files. Sarcopenia was defined as a muscle area index below the 5th percentile of the general population. Uni- and multivariable analyses were performed to assess the association between sarcopenia and hospital mortality, correcting for age and comorbidities.

Results: The prevalence of sarcopenia was higher in patients that did not survive until hospital discharge. However, it appeared that this relation was confounded by the presence of chronic renal insufficiency and cancer. These were independent risk factors for hospital mortality, whereas sarcopenia was not.

Conclusion: In critically ill patients with abdominal sepsis, muscle wasting associated co-morbidities rather than sarcopenia were risk factors for hospital mortality.
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http://dx.doi.org/10.1016/j.jcrc.2019.11.016DOI Listing
April 2020

Variability of Microcirculatory Measurements in Critically Ill Patients.

Shock 2020 07;54(1):9-14

Department of Biochemistry, Maastricht University, Maastricht, the Netherlands.

Introduction: Monitoring the microcirculation may be helpful in guiding resuscitation in patients with circulatory shock. Sublingual side-stream dark field imaging cameras allow for noninvasive, bedside evaluation of the microcirculation, although their use in clinical practice has not yet been validated. The GlycoCheck system automatically analyzes images to determine glycocalyx thickness, red blood cell filling percentage, and vessel density. Although GlycoCheck has been used to study microcirculation in critically ill patients, little is known about the reproducibility of measurements in this population.

Materials And Methods: A total of 60 critically ill patients were studied. Three consecutive microcirculation measurements were performed with the GlycoCheck system in 40 of these patients by one of two experienced observers. Twenty patients were assessed by both observers. Intra- and interobserver variability were assessed using intraclass correlation coefficients (ICCs).

Results: ICCs of single measurements were poor for glycocalyx thickness and good for filling percentage and vessel density. Reproducibility could be substantially increased for all parameters when three consecutive measurements were performed and averaged.

Discussion: GlycoCheck can be used to study microcirculation. However, to obtain reliable results three consecutive measurements should be performed and averaged. The variation of the measurements currently hampers the clinical application in individual patients.
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http://dx.doi.org/10.1097/SHK.0000000000001470DOI Listing
July 2020

Early initiation of extracorporeal life support in refractory out-of-hospital cardiac arrest: Design and rationale of the INCEPTION trial.

Am Heart J 2019 04 14;210:58-68. Epub 2018 Dec 14.

Department of Intensive Care, Maastricht University Medical Center, Maastricht, The Netherlands; NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands; Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands.

Return of spontaneous circulation occurs in less than 10% of patients with cardiac arrest undergoing cardiopulmonary resuscitation (CPR) for more than 15 minutes. Studies suggest that extracorporeal life support during cardiopulmonary resuscitation (ECPR) improves survival rate in these patients. These studies, however, are hampered by their non-randomized, observational design and are mostly single-center. A multicenter, randomized controlled trial is urgently warranted to evaluate the effectiveness of ECPR.

Hypothesis: We hypothesize that early initiation of ECPR in refractory out-of-hospital cardiac arrest (OHCA) improves the survival rate with favorable neurological status.

Study Design: The INCEPTION trial is an investigator-initiated, prospective, multicenter trial that will randomly allocate 110 patients to either continued CPR or ECPR in a 1:1 ratio. Patients eligible for inclusion are adults (≤ 70 years) with witnessed OHCA presenting with an initial rhythm of ventricular fibrillation (VF) or ventricular tachycardia (VT), who received bystander basic life support and who fail to achieve sustained return of spontaneous circulation within 15 minutes of cardiopulmonary resuscitation by emergency medical services. The primary endpoint of the study is 30-day survival rate with favorable neurological status, defined as 1 or 2 on the Cerebral Performance Category score. The secondary endpoints include 3, 6 and 12-month survival rate with favorable neurological status and the cost-effectiveness of ECPR compared to CCPR.

Summary: The INCEPTION trial aims to determine the clinical benefit for the use of ECPR in patients with refractory OHCA presenting with VF/VT. Additionally, the feasibility and cost-effectiveness of ECPR will be evaluated.
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http://dx.doi.org/10.1016/j.ahj.2018.12.008DOI Listing
April 2019

Clinical implementation of electric impedance tomography in the treatment of ARDS: a single centre experience.

J Clin Monit Comput 2019 Apr 29;33(2):291-300. Epub 2018 May 29.

Department of Intensive Care, Maastricht University Medical Centre+, P. Debyelaan 25, 6229HX, Maastricht, The Netherlands.

To report on our clinical experience using EIT in individualized PEEP titration in ARDS. Using EIT assessment, we optimized PEEP settings in 39 ARDS patients. The EIT PEEP settings were compared with the physicians' PEEP settings and the PEEP settings according to the ARDS network. We defined a PEEP difference equal to or greater than 4 cm HO as clinically relevant. Changes in lung compliance and PaO/FiO-ratio were compared in patients with EIT-based PEEP adjustments and in patients with unaltered PEEP. In 28% of the patients, the difference in EIT-based PEEP and physician-PEEP was clinically relevant; in 36%, EIT-based PEEP and physician-PEEP were equal. The EIT-based PEEP disagreed with the PEEP settings according to the ARDS network. Adjusting PEEP based upon EIT led to a rapid increase in lung compliance and PaO/FiO-ratio. However, this increase was also observed in the group where the PEEP difference was less than 4 cm HO. We hypothesize that this can be attributed to the alveolar recruitment during the PEEP trial. EIT based individual PEEP setting appears to be a promising method to optimize PEEP in ARDS patients. The clinical impact, however, remains to be established.
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http://dx.doi.org/10.1007/s10877-018-0164-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420412PMC
April 2019

A Modified Technique to Create a Standardized Floppy Nissen Fundoplication Without a Bougie.

J Laparoendosc Adv Surg Tech A 2018 Jul 21;28(7):853-858. Epub 2018 Feb 21.

4 Department of Surgery, Catharina Hospital Eindhoven , Eindhoven, The Netherlands .

Introduction: Nissen fundoplication is frequently applied in the surgical treatment of patients with gastroesophageal reflux disease (GERD). When the gastroesophageal junction remains too large or becomes too narrow, persistent GERD or dysphagia may occur. To assure a correct size of the gastroesophageal junction, the fundoplication can be created over a bougie. However, this increases the risk of esophageal perforation. Therefore, we have modified a previously described technique to create a standardized fundoplication without the use of a bougie. In this article, we describe this technique and demonstrate the initial results.

Materials And Methods: We describe a technique to create a standardized Nissen fundoplication. After suture repair of the hiatal hernia, three marking sutures were placed on the gastric fundus, based on an equilateral triangle. The size of this triangle determines the final diameter of the fundoplication. With these measurements, we assure sufficient patency, minimize rotation, and create a more reproducible fundoplication that may reduce postoperative dysphagia.

Results: We have operated 15 patients according to this technique. Mean operative time was 69.5 (SD 8.4) minutes, no complications occurred. There was no early dysphagia and the mean length of stay was 1.3 days (1-2). Quality of life after 1 year was excellent.

Conclusions: This modified method for standardized Nissen fundoplication is safe and might reduce postoperative dysphagia. Quality of life after 1 year is excellent. The effect on postoperative dysphagia and the reproducibility of this technique should be established in a large prospective study.
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http://dx.doi.org/10.1089/lap.2017.0734DOI Listing
July 2018

The influence of a change in septic shock definitions on intensive care epidemiology and outcome: comparison of sepsis-2 and sepsis-3 definitions.

Infect Dis (Lond) 2018 03 26;50(3):207-213. Epub 2017 Sep 26.

a Department of Intensive Care Medicine , Maastricht University Medical Centre , Maastricht , The Netherlands.

Background: Clear definitions for septic shock assist clinicians regarding recognition, treatment and standardized reporting of characteristics and outcome of this entity. Sepsis-3 definition of septic shock incorporates a new criterion, a lactate level >2 mmol/L. Differences in epidemiology and outcome of septic shock based upon both definitions were studied in an intensive care (ICU) population of septic patients.

Methods: We analyzed a prospectively collected cohort of data in the ICU of the Maastricht University Medical Centre. 632 septic patients were included. ICU mortality was compared between the patient group fulfilling Sepsis-3 definition for septic shock and those that met Sepsis-2 definition. Furthermore, association between lactate levels and ICU mortality was studied.

Results: Of 632 septic patients, 482 (76.3%) had septic shock according to Sepsis-2 and 300 patients (48.4%) according to Sepsis-3 definition, respectively. Patients meeting Sepsis-3 definition had a higher mortality than patients meeting Sepsis-2 definition (38.9 vs. 34.0%). Serum lactate levels between 2 and 4 mmol/L (25.0 vs. 26.2%, OR 0.94 (0.5-1.5)) and between 4 and 6 mmol/L (23.8 vs. 26.2%, OR 0.88 (0.4-1.7)) compared to levels ≤2 mmol/L were not associated with significantly higher ICU mortality. Serum lactate values ≥6 mmol/L, were significantly associated with increased ICU mortality.

Conclusion: Patients classified according to Sepsis-3 criteria had a higher ICU mortality compared with Sepsis-2 criteria. Lactate levels <6 mmol/L were not able to identify patients with increased ICU mortality. Lactate threshold of 2 mmol/L may be too low to point out patients with actual increased ICU mortality.
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http://dx.doi.org/10.1080/23744235.2017.1383630DOI Listing
March 2018

Increased Dicarbonyl Stress as a Novel Mechanism of Multi-Organ Failure in Critical Illness.

Int J Mol Sci 2017 Feb 7;18(2). Epub 2017 Feb 7.

Department of Intensive Care, Maastricht University Medical Centre +, Maastricht 6229 HX, The Netherlands.

Molecular pathological pathways leading to multi-organ failure in critical illness are progressively being unravelled. However, attempts to modulate these pathways have not yet improved the clinical outcome. Therefore, new targetable mechanisms should be investigated. We hypothesize that increased dicarbonyl stress is such a mechanism. Dicarbonyl stress is the accumulation of dicarbonyl metabolites (i.e., methylglyoxal, glyoxal, and 3-deoxyglucosone) that damages intracellular proteins, modifies extracellular matrix proteins, and alters plasma proteins. Increased dicarbonyl stress has been shown to impair the renal, cardiovascular, and central nervous system function, and possibly also the hepatic and respiratory function. In addition to hyperglycaemia, hypoxia and inflammation can cause increased dicarbonyl stress, and these conditions are prevalent in critical illness. Hypoxia and inflammation have been shown to drive the rapid intracellular accumulation of reactive dicarbonyls, i.e., through reduced glyoxalase-1 activity, which is the key enzyme in the dicarbonyl detoxification enzyme system. In critical illness, hypoxia and inflammation, with or without hyperglycaemia, could thus increase dicarbonyl stress in a way that might contribute to multi-organ failure. Thus, we hypothesize that increased dicarbonyl stress in critical illness, such as sepsis and major trauma, contributes to the development of multi-organ failure. This mechanism has the potential for new therapeutic intervention in critical care.
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http://dx.doi.org/10.3390/ijms18020346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343881PMC
February 2017

Steroid use is associated with clinically irrelevant biopsies in patients with suspected giant cell arteritis.

Am Surg 2012 Dec;78(12):1362-8

Department of Surgery, Catharina Hospital Eindhoven, Eindhoven, The Netherlands.

Temporal artery biopsy (TAB) is the diagnostic gold standard for giant cell arteritis (GCA). GCA is treated by high-dose corticosteroids. In cases of high clinical suspicion, steroids may be administrated despite negative TAB, making TAB clinically irrelevant. We assessed the role of TAB in clinical decision-making in patients with suspected GCA and to identify factors associated with clinically irrelevant TAB. Charts of patients who underwent TAB from 2005 to 2010 were reviewed for clinical parameters potentially associated with GCA and clinically irrelevant TAB. We studied 143 patients with 99 negative (69%), 34 positive (24%), and 10 undefined (7%) TABs. Eventually 26 patients (18% of the entire cohort and 26% of the patients with a negative TAB) received steroid treatment for GCA despite negative TAB. The start of steroid treatment before TAB was associated with clinically irrelevant TABs. If clinical suspicion of GCA is high, a TAB can be considered clinically irrelevant.
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December 2012

[13-Year old boy with abdominal pain].

Ned Tijdschr Geneeskd 2012 ;156(18):A3566

Catharina-ziekenhuis, afd. Chirurgie, Eindhoven, the Netherlands.

A 13-year old boy presents with pain in the lower right abdomen, showing clinical signs of appendicitis. During McBurney' incision an appendix sana was seen. Histologic examination showed penetrating enterobiasis. This was treated with mebendazol.
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June 2012

Urinary ammonia excretion increases acutely during living donor liver transplantation.

Liver Int 2011 Sep 12;31(8):1150-4. Epub 2011 May 12.

Department of Surgery, Maastricht University, Maastricht, the Netherlands.

Introduction: Arterial ammonia concentrations increase acutely during the anhepatic phase of a liver transplantation (LTx) and return to baseline within 1 h after reperfusion of a functioning liver graft. So far, this return to baseline has solely been attributed to hepatic ammonia clearance. No data exist on the potential contribution of altered renal ammonia handling to peritransplantation ammonia homoeostasis.

Aim: The present study investigated the consequences of a hepatectomy and subsequent implantation of a partial liver graft on arterial ammonia concentrations and urinary ammonia excretion during a living donor liver transplantation (LDLTx).

Methods: Patients with end-stage liver disease undergoing LDLTx were selected. Samples of arterial blood and urine were taken before, during and 2 h after the anhepatic phase. Differences were tested using Wilcoxon's test. Results are given as median and range.

Results: Eleven adult patients undergoing an LDLTx were included. Before hepatectomy, arterial ammonia concentrations were 89 μM (40-156 μM), increasing to 146 μM (102-229 μM) (P<0.001) during the anhepatic phase and returning to 79 μM (46-111 μM) (P<0.01) after reperfusion. Urinary ammonia excretion was initially 1.06 mmol/h (0.02-6.00 mmol/h), increasing to 3.81 mmol/h (0.32-12.55 mmol/h) (P=0.004) during the anhepatic phase and further increasing to 4.00 mmol/h (0.79-9.51 mmol/h) (P=0.013) after reperfusion.

Conclusion: The kidney significantly increased urinary ammonia excretion during the anhepatic phase, which was sustained after reperfusion, contributing to the rapid decrease of ammonia concentrations. Accordingly, the plasma ammonia concentrations measured directly after LTx cannot simply be used as a read-out of initial liver graft function.
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http://dx.doi.org/10.1111/j.1478-3231.2011.02544.xDOI Listing
September 2011

Accurate perioperative flow measurement of the portal vein and hepatic and renal artery: a role for preoperative MRI?

Eur J Radiol 2012 Sep 2;81(9):2042-8. Epub 2011 Jul 2.

Department of Surgery, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.

Background: Quantification of abdominal blood flow is essential for a variety of gastrointestinal and hepatic topics such as liver transplantation or metabolic flux measurement, but those need to be performed during surgery. It is not clear whether Duplex Doppler Ultrasound during surgery or MRI before surgery is the tool to choose.

Objective: To examine whether preoperative evaluation of abdominal blood flow using MRI could prove to be a useful and reliable alternative for the perioperative sonographic approach.

Methods: In this study portal and renal venous flow and hepatic arterial flow were sequentially quantified by preoperative MRI, preoperative and perioperative Duplex Doppler Ultrasound (DDUS). 55 Patients scheduled for major abdominal surgery were studied and methods and settings were compared. Additionally, average patient population values were compared.

Results: Mean (±SD) plasmaflow measured by perioperative DDUS, preoperative DDUS and MRI, respectively was 433±200/423±162/507±96 ml/min (portal vein); 96±70/74±41/108±91 ml/min (hepatic artery); 248±139/201±118/219±69 ml/min (renal vein). No differences between the different settings of DDUS measurement were detected. Equality of mean was observed for all measurements. Bland Altman Plots showed widespread margins. Hepatic arterial flow measurements correlated with each other, but portal and renal venous flow correlations were absent.

Conclusions: Surgery and method (DDUS vs. MRI) do not affect mean flow values. Individual comparison is restricted due to wide range in measurements. Since MRI proves to be more reliable with respect to inter-observer variability, we recommend using mean MRI results in experimental setups.
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http://dx.doi.org/10.1016/j.ejrad.2011.06.023DOI Listing
September 2012

To pee or not to pee: ammonia hypothesis of hepatic encephalopathy revisited.

Eur J Gastroenterol Hepatol 2011 Jun;23(6):449-54

Department of Surgery, Maastricht University Medical Centre, and School of Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands.

Hepatic encephalopathy is a neuropsychiatric syndrome associated with liver failure. Its aetiology has been debated for the past 100 years. Nevertheless, elevated ammonia levels are still believed to play a central role in its pathogenesis. After intestinal production, ammonia is detoxified by the liver. In liver failure, skeletal muscle and brain have been proposed to be alternative, although temporary, ammonia detoxifying organs. However, there is an increasing body of evidence that the kidney, in addition to the gut, is a pivotal organ determining systemic ammonia levels. In the last 20 years, it has been shown that the kidney can switch from an organ of systemic net ammonia production to a net ammonia excretion organ. The kidney plays a central role in the determination of ammonia levels. It is at least as important as the gut and could therefore serve as a target for new treatments for hepatic encephalopathy.
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http://dx.doi.org/10.1097/MEG.0b013e328346a7bdDOI Listing
June 2011

Gut and liver handling of interleukin-6 during liver resection in man.

HPB (Oxford) 2011 May 7;13(5):324-31. Epub 2011 Mar 7.

Department of Surgery, Maastricht University Medical Center & Nutrim School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, the Netherlands.

Background: Plasma interleukin-6 (IL-6) levels increase during liver resection. The source of this IL-6 is hitherto unclear. It has been demonstrated that the hepatosplanchnic area takes up IL-6 but the role of the gut and liver is unknown. The aim of the present study was to investigate the role of the gut and liver in IL-6 homeostasis during liver surgery.

Methods: Before and after partial hepatectomy, IL-6 was measured in blood sampled from the radial artery, and the hepatic and portal vein. Blood flow was measured to assess IL-6 fluxes (flow times AV-differences) across the gut, liver and hepatosplanchnic area.

Results: In 22 patients undergoing liver resection, IL-6 release from the gut after transection was 90.9 (30.1) ng/min (P < 0.001), whereas net IL-6 uptake by the liver equalled 83.4 (41.7) ng/min (P < 0.01). Overall hepatosplanchnic flux was 7.3 (43.5) ng/min after transection and did not differ significantly from zero. Overall hepatosplanchnic flux was 87.8 (41.5) ng/min in the major resection group and -59.8 (67.5) ng/min in the minor resection group (P < 0.05).

Discussion: The gut releases IL-6 and the liver takes up IL-6 before and after liver resection. The loss of IL-6 uptake as a result of a small functional remnant liver could lead to higher IL-6 levels after surgery.
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http://dx.doi.org/10.1111/j.1477-2574.2010.00289.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093644PMC
May 2011
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