Paul A M van Leeuwen

VU University Amsterdam, Amsterdamo, North Holland, Netherlands

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Publications (158)793.27 Total impact

  • No preview · Article · Jan 2016 · Journal of Parenteral and Enteral Nutrition
  • C. Oude Ophuis · C. Verhoef · P. Rutkowski · C. Voit · M. Cook · P. Van Leeuwen · A. Testori · H. Hoekstra · D. Grünhagen · A. Eggermont · A. Van Akkooi

    No preview · Article · Sep 2015

  • No preview · Article · Aug 2015 · Plastic & Reconstructive Surgery
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    ABSTRACT: Major surgery induces a long fasting time and provokes an inflammatory response which increases the risk of infections. Nutrition given before and during surgery can avoid fasting and has been shown to increase the arginine/asymmetric dimetlhylarginine ratio, a marker of nitric oxide availability, in cardiac tissue and increased concentrations of branched chain amino acids in blood plasma. However, the effect of this new nutritional strategy on organ inflammatory response is unknown. Therefore, we studied the effect of nutrition before and during cardiac surgery on myocardial inflammatory response. In this trial, 32 patients were randomised between enteral, parenteral, and no nutrition supplementation (control) from 2 days before, during, up to 2 days after coronary artery bypass grafting. Both solutions included proteins or amino acids, glucose, vitamins, and minerals. Myocardial atrial tissue was sampled before and after revascularization and was analysed immunohistochemically, subdivided into cardiomyocytic, fatty, and fibrotic areas. Inflammatory cells, especially leukocytes, were present in cardiac tissue in all study groups. No significant differences were found in the myocardial inflammatory response between the enteral, parenteral, and control groups. In conclusion, nutrition given before and during surgery neither stimulates nor diminishes the myocardial inflammatory response in patients undergoing coronary artery bypass grafting. The trial was registered in Netherlands Trial Register (NTR): NTR2183 .
    No preview · Article · Aug 2015 · Journal of nutrition and metabolism
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    ABSTRACT: Excision followed by adjuvant irradiation is considered safe and most efficacious for treatment of keloid scars. Recently, different authors published successful treatment protocols and recommended the following: (1) the use of high-dose-rate brachytherapy instead of low-dose-rate brachytherapy or external radiation; (2) a short-time interval between operation and irradiation; (3) single fraction instead of multifraction irradiation; and (4) a minimum of 12- to 24-month follow-up post treatment. This study evaluates the above recommendations with a systematic review of the English-language literature, based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. Both PubMed and EMBASE were searched. Studies were graded according to the American Society of Plastic Surgeons Rating Levels of Evidence. Thirty-three studies were selected. Six studies were graded as level of evidence type II studies and 27 as type III. High-dose-rate brachytherapy showed lower recurrence rates compared with low-dose-rate brachytherapy and external radiation. A short-time (<7 hours) interval between scar excision and irradiation results in a lower recurrence rate compared with long-time intervals (>24 hours). Single-fraction irradiation showed promising results in terms of recurrence rate and patient convenience. Finally, scar recurrences were seen between 2 and 36 months, with a mean of 15 months. Based on this systematic review of the literature, the evidence confirms the recommendations stated by authors in the recent years. However, due to the lack of high-quality randomized studies, the quality of this evidence is limited. More randomized studies will generate stronger recommendations.
    Full-text · Article · Jul 2015
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    ABSTRACT: Intralesional (IL) cryotherapy is a novel treatment technique for keloid scars, in which the scar is frozen from inside. Over the past decade, several studies have been published with varying outcomes. A critical analysis of the current literature is, therefore, warranted to determine whether IL cryotherapy is an alternative to established keloid scar treatments. A comprehensive review was performed, based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. PubMed and EMBASE were searched from inception. Studies and level of recommendation were graded according to the American Society of Plastic Surgeons criteria. Eight studies meeting the inclusion criteria were selected. The average scar volume decrease ranged from 51% to 63%, but no complete scar eradication was achieved on average. Scar recurrence ranged from 0% to 24%. Hypopigmentation posttreatment was seen mostly in Fitzpatrick 4-6 skin type patients. Finally, complaints of pain and pruritus decreased significantly in most studies. IL cryotherapy for the treatment of keloid scars shows favorable results in terms of volume reduction and alleviated complaints of pain and pruritus. However, no complete scar eradication is established, and recurrences are seen. Also, persistent hypopigmentation proved a problem in Fitzpatrick 4-6 skin type patients. Summarized, the evidence proved limited and inconsistent resulting in an American Society of Plastic Surgeons grade C recommendation for this type of treatment of keloid scars.
    Full-text · Article · Jun 2015
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    ABSTRACT: Hip fracture patients represent a large part of the elderly surgical population and face severe postoperative morbidity and excessive mortality compared to adult surgical hip fracture patients. Low antioxidant status and taurine deficiency is common in the elderly, and may negatively affect postoperative outcome. We hypothesized that taurine, an antioxidant, could improve clinical outcome in the elderly hip fracture patient. A double blind randomized, placebo controlled, clinical trial was conducted on elderly hip fracture patients. Supplementation started after admission and before surgery up to the sixth postoperative day. Markers of oxidative status were measured during hospitalization, and postoperative outcome was monitored for one year after surgery. Taurine supplementation did not improve in-hospital morbidity, medical comorbidities during the first year, or mortality during the first year. Taurine supplementation lowered postoperative oxidative stress, as shown by lower urinary 8-hydroxy-2-deoxyguanosine levels (Generalized estimating equations (GEE) analysis average difference over time; regression coefficient (Beta): -0.54; 95% CI: -1.08--0.01; p = 0.04), blunted plasma malondialdehyde response (Beta: 1.58; 95% CI: 0.00-3.15; p = 0.05) and a trend towards lower lactate to pyruvate ratio (Beta: -1.10; 95% CI: -2.33-0.12; p = 0.08). We concluded that peri-operative taurine supplementation attenuated postoperative oxidative stress in elderly hip fracture patients, but did not improve postoperative morbidity and mortality.
    Full-text · Article · Jun 2015 · International Journal of Molecular Sciences
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    ABSTRACT: Unlabelled: Supplementation with arginine in combination with atorvastatin is more efficient in reducing the size of an atherosclerotic plaque than treatment with a statin or arginine alone in homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits. We evaluated the mechanism behind this feature by exploring the role of the arginine/asymmetric dimethylarginine (ADMA) ratio, which is the substrate and inhibitor of nitric oxide synthase (NOS) and thereby nitric oxide (NO), respectively. Methods: Rabbits were fed either an arginine diet (group A, n = 9), standard rabbit chow plus atorvastatin (group S, n = 8), standard rabbit chow plus an arginine diet with atorvastatin (group SA, n = 8) or standard rabbit chow (group C, n = 9) as control. Blood was sampled and the aorta was harvested for topographic and histological analysis. Plasma levels of arginine, ADMA, cholesterol and nitric oxide were determined and the arginine/ADMA ratio was calculated. Results: The decrease in ADMA levels over time was significantly correlated to fewer aortic lesions in the distal aorta and total aorta. The arginine/ADMA ratio was correlated to cholesterol levels and decrease in cholesterol levels over time in the SA group. A lower arginine/ADMA ratio was significantly correlated to lower NO levels in the S and C group. Discussion: A balance between arginine and ADMA is an important indicator in the prevention of the development of atherosclerotic plaques.
    Full-text · Article · May 2015 · International Journal of Molecular Sciences
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    ABSTRACT: Malignancies induce disposal of arginine, an important substrate for the immune system. To sustain immune function, the tumor-bearing host accelerates arginine's intestinal-renal axis by glutamine mobilization from skeletal muscle and this may promote cachexia. Glutamine supplementation stimulates argi-nine production in healthy subjects. Arginine's intestinal-renal axis and the effect of glutamine supplementation in cancer cach-exia have not been investigated. This study evaluated the long-term adaptations of the interorgan pathway for arginine production following the onset of cachexia and the metabolic effect of glutamine supplementation in the cachectic state. Fischer-344 rats were randomly divided into a tumor-bearing group (n = 12), control group (n = 7) and tumor-bearing group receiving a glutamine-enriched diet (n = 9). Amino acid fluxes and net fractional extractions across intestine, kidneys, and liver were studied. Compared to controls, the portal-drained viscera of tumor-bearing rats took up significantly more glutamine and released significantly less citrulline. Renal metabolism was unchanged in the cachectic tumor-bearing rats compared with controls. Glutamine supplementation had no effects on intestinal and renal adaptations. In conclusion, in the cachectic state, an increase in intestinal glutamine uptake is not accompanied by an increase in renal arginine production. The adaptations found in the cachectic, tumor-bearing rat do not depend on glutamine availability.
    No preview · Article · Apr 2015 · Nutrition and Cancer
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    ABSTRACT: Intralesional cryotherapy is a novel treatment for keloid scars in which the scar is frozen from inside. Published results are promising, but the treatment has only been tested in a Caucasian patient population. Therefore, the authors evaluated intralesional cryotherapy in a patient population including different Fitzpatrick skin types (I through VI). This prospective multicenter study with a 1-year follow-up included 27 patients with 29 keloid scars. Intralesional cryotherapy was administered with a disposable liquid nitrogen-based device called CryoShape. Scar assessment was performed using the Patient and Observer Scar Assessment Scale and four objective devices to determine scar color, scar elasticity, scar volume, and patient skin type. Keloid scars showed an average volume decrease of 63 percent (range, 16 to 100 percent) after 12 months, compared with baseline (p < 0.01). Recurrence was seen in seven keloids (24 percent) and hypopigmentation recovered in 69 percent of all keloid scars within 12 months. Scar assessment with the Patient and Observer Scar Assessment Scale showed an overall improvement according to both doctors and patients. In addition, complaints of pain and itching were reduced. When analyzing the results per Fitzpatrick skin type, African American patients showed a higher incidence of persistent hypopigmentation (p = 0.02). Intralesional cryotherapy for the treatment of keloid scars shows favorable results in terms of reduction of volume and complaints of pain and pruritus. However, no complete eradication was obtained in some cases and recurring scars were seen. In addition, persistent hypopigmentation proved a problem in non-Caucasian patients. Therapeutic, IV.
    No preview · Article · Feb 2015 · Plastic & Reconstructive Surgery
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    ABSTRACT: Background: Nutrition studies in the intensive care unit (ICU) have shown that adequate enteral nutrition (EN) support has clinical benefits. However, the course of amino acid concentrations in plasma has never been investigated in patients admitted with shock receiving EN. We hypothesized that plasma concentrations, when deficit, increase during EN and that persistent deficiency is associated with poor outcome. Methods: In 33 septic or cardiogenic shock patients receiving EN, plasma amino acid concentrations were measured during 5 days. Changes in amino acid concentrations, correlations with clinical outcome variables, and regression analyses were studied. Results: On ICU admission, several plasma concentrations were deficient. Plasma concentrations of almost all amino acids increased. In contrast, taurine decreased by >50%, from 47.6 µmol/L on admission to 20.0 µmol/L at day 1, and remained low at day 5. Taurine (admission) correlated with time on mechanical ventilation (R = -0.42, P = .015). Taurine decrease within 24 hours correlated with Acute Physiology and Chronic Health Evaluation II predicted mortality (R = 0.43, P = .017) and Sequential Organ Failure Assessment score (R = 0.36, P = .05). Regression analyses confirmed correlations. Conclusions: Several amino acids were deficient in plasma on ICU admission but increased during EN. Taurine concentrations declined and were associated with longer periods of mechanical ventilation and ICU support. Fast taurine decline correlated with severity of organ failure. These findings support the role of taurine during ischemia, reperfusion, and inflammation. Taurine may be an essential candidate to enrich nutrition support for critically ill patients, although more research is required. © 2015 American Society for Parenteral and Enteral Nutrition.
    Full-text · Article · Jan 2015 · Journal of Parenteral and Enteral Nutrition
  • Nikki Buijs · Paul A M van Leeuwen

    No preview · Article · Dec 2014 · JAMA The Journal of the American Medical Association

  • No preview · Article · Sep 2014

  • No preview · Article · Sep 2014
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    ABSTRACT: Background: Keloids cause aesthetic disfigurement and physical complaints, mainly pain and pruritus. Treatment of these scars is difficult, with high recurrence rates forming the main issue. Surgical excision with adjuvant radiotherapy is considered the most efficacious treatment. At their institution, the authors have been treating keloids with a high-dose-rate brachytherapy procedure for over 10 years, using a protocol with the lowest total radiation dosage known in the literature. Methods: This prospective study included 43 patients of all Fitzpatrick skin types, with 67 keloids in total. After extralesional excision, a radiation scheme of 2 x 6 Gy was administered in two fractions: the first within 4 hours after surgery and the second within 24 hours. Scars were measured and recurrence was judged. Scar appearance was evaluated using the Patient and Observer Scar Assessment Scale. Results: The recurrence rate was 3.1 percent at a mean follow-up of 33.6 months. A significant average scar surface decrease of 56.7 percent was measured (p = 0.01). Complaints of pain and pruritus decreased by 82.9 and 87.2 percent, respectively. Patients were satisfied with the treatment in 88.6 percent of the cases and with the cosmetic result in 77.1 percent. Pigmentation problems were seen in 21.4 percent of the patients, mostly in Fitzpatrick type V and VI/African American individuals. Conclusions: The results of this prospective study show a good cosmetic outcome with a low recurrence rate. The unique radiation schedule proves the efficacy and safety of high-dose-rate brachytherapy and suggests the importance of immediate postoperative irradiation. In addition, only one outpatient treatment is required after surgery, enhancing patient convenience.
    No preview · Article · Sep 2014 · Plastic & Reconstructive Surgery
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    ABSTRACT: Background Intralesional (IL) cryotherapy is a new promising technique for the treatment of keloid scars, in which the scar is frozen from inside. Multiple devices are available, mostly based on a simple liquid nitrogen Dewar system, which have a limited freezing capacity. Argon gas based systems ensure accurate and highly controlled freezing and have shown effective within the field of oncologic surgery. However, this technique has never been used for treatment of keloid scars. Objective This prospective study evaluates an argon gas based system for the treatment of keloids in a patient population including all Fitzpatrick skin types with a 1 year follow-up. Methods Twenty-five patients with 30 keloid scars were included and treated with a device called Seednet. Scar quality and possible scar recurrence were assessed pre- and post-treatment (6 and 12 months) with objective devices determining scar color, scar elasticity, scar volume and patient’s skin type. In addition, scars were evaluated using the Patient and Observer Scar Assessment Scale. Results After 12 months, a significant volume reduction of 62% was obtained, p=0,05. Moreover, complaints of pain and itching were alleviated and scar quality had improved according to the Patient and Observer Scar Assessment Scale. Scar pigmentation recovered in 62% of all keloid scars within 12 months. Five out of 30 (17%) scars recurred within 12 months, 3 of which had previously been treated with liquid nitrogen-based IL cryotherapy. Both recurrence and persistent hypopigmentation were mainly seen in Afro-American patients. Conclusions Intralesional cryotherapy with the use of an argon gas based system proves to be effective in the treatment of keloid scars, yielding volume reduction and low recurrence rates. Although hypopigmentation recovered in most cases, it is strongly related to non- Caucasian patients. Finally, additional treatment of keloid scars previously unresponsive to IL cryotherapy, are predisposed to a high recurrence rate. Trial number NCT02063243.
    Full-text · Article · Aug 2014 · Journal of Plastic Reconstructive & Aesthetic Surgery
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    ABSTRACT: A serious complication seen in critically ill patients is the solidification of enteral nutrition causing gastrointestinal obstruction. It has been suggested that enteral nutrition enriched with insoluble fibers may increase the risk of this complication. Therefore, we investigate the effect of soluble and insoluble dietary fibers on the coagulation of a casein-based enteral nutrition in an artificial gastric digestion model. A 100% casein-based enteral nutrition was enriched with increasing concentrations of soluble fibers (acacia fiber, oligofructose and inulin) and insoluble fibers (soy polysaccharide, resistant starch and alpha cellulose). After digestion in an artificial gastric model, the chyme was poured over sequentially placed sieves, separating the coagulate into size fractions of larger than 2 mm, between 1 and 2 mm, and between 0.25 and 1 mm. Of these fractions we measured wet weight, dry weight and protein content. A significant effect on the fraction larger than 2 mm was considered to be clinically relevant. Addition of high concentrations soy polysaccharide and resistant starch to a casein-based enteral nutrition, did not alter the wet weight, whereas dry weight and protein content of the coagulate was significantly reduced. When high concentrations of soy polysaccharide and resistant starch are added to a 100% casein-based enteral nutrition, the coagulate consist of more water and less proteins, which may lead to an increased protein digestion and absorption in a clinical setting. The suggestion that insoluble fibers increase the risk of gastrointestinal obstruction in critically ill patients is not supported by these data.
    No preview · Article · Jun 2014 · Food & Function
  • Saskia J.H. Brinkmann · Myrte C de Boer · Nikki Buijs · Paul A.M. van Leeuwen
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    ABSTRACT: Asymmetric dimethylarginine (ADMA) is an analog of arginine and functions as an endogenous inhibitor of the nitric oxide synthase, which forms nitric oxide. Nitric oxide is crucial for perfusion of vital organs and is an important signaling agent in the development of critical illness. The role of ADMA in the pathophysiological mechanisms underlying critical illness is widely studied in the last decades, and recently it has become clear that ADMA should not be overlooked by clinicians working at the ICU. The aim of this review is to describe new insights into the role of ADMA in critical illness and its clinical relevance. High levels of ADMA are found in critically ill patients, because of higher levels of protein methylation, increased rate of protein turnover, decreased activity of dimethylamine dimethylaminohydrolase, and impaired renal and hepatic clearance capacity. These high levels are an independent risk factor for cardiac dysfunction, organ failure, and ICU mortality. The arginine : ADMA ratio in particular is of clinical importance and the restoration of this ratio is expedient to restore several functions that are disturbed during critical illness. Elevated ADMA levels occur in critically ill patients, which is detrimental for morbidity and mortality. The arginine : ADMA ratio should be restored to maintain nitric oxide production and therewith improve the clinical outcome of the patient.
    No preview · Article · Nov 2013
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    Nikki Buijs · Mechteld A R Vermeulen · Paul A M van Leeuwen
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    ABSTRACT: To the Editor: Heyland et al. (April 18 issue)(1) have shown that glutamine supplementation (approximately 65 g daily) of a diet that does not supply adequate energy (910 kcal) or protein (45 g) did not affect clinical outcome and increased mortality. However, the addition of a supplement that constituted 60% of total dietary protein introduced an amino acid imbalance with the potential for toxicity. Other, similar examples, such as the lack of arginine as part of dietary protein(2) or the use of essential amino acids only(3) in otherwise complete diets, have been shown to produce hyperammonemia in humans. Furthermore, glutamine . . .
    Full-text · Article · Aug 2013 · New England Journal of Medicine
  • Joanna Luttikhold · Klaske van Norren · Nikki Buijs · Herman Rijna · Paul A.M. van Leeuwen
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    ABSTRACT: Introduction: Solidification of enteral nutrition may cause gastrointestinal obstruction, with severe complications. The effect of the composition of enteral nutrition on the tendency of casein to coagulate is increasingly acknowledged and new formulas may prevent solidification. To recognize patients in need of specific enteral nutrition, we have to identify the clinical risk factors for the development of gastrointestinal obstruction by the solidification of enteral nutrition. Materials and methods: The 58 cases summarized in this review were identified through a PubMed search. Results: Critically ill patients have several risk factors, including impaired digestion, and they are treated with medication that interferes with gastrointestinal function. Surgery of the upper gastrointestinal tract is thought to be the most important risk factor, leading to changes in both the anatomical structure and neurohormonal functioning of the gastrointestinal tract, and to altered secretion of digestive enzymes. Conclusions: Awareness of risk factors in critically ill patients may help intensivists and surgeons take appropriate measures to prevent this complication. Critically ill patients with impaired digestion (e.g. after Whipple surgery) should be considered for alternative enteral nutrition formulas with noncoagulating proteins or hydrolyzed proteins.
    No preview · Article · Jul 2013 · Nutritional Therapy and Metabolism

Publication Stats

4k Citations
793.27 Total Impact Points


  • 1999-2016
    • VU University Amsterdam
      • Department of Surgery
      Amsterdamo, North Holland, Netherlands
  • 2015
    • Academisch Medisch Centrum Universiteit van Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 2002-2015
    • VU University Medical Center
      • • Department of Surgery
      • • Department of Pathology
      • • Department of Molecular Cell Biology and Immunology
      Amsterdamo, North Holland, Netherlands
    • Technische Universität München
      München, Bavaria, Germany
  • 1999-2008
    • University of Amsterdam
      • • Department of Surgery
      • • Department of Chemistry
      • • Department of Plant Physiology
      • • Institute for Neurobiology
      Amsterdamo, North Holland, Netherlands
  • 2005
    • Erasmus MC
      Rotterdam, South Holland, Netherlands
  • 2000
    • Freie Universität Berlin
      Berlín, Berlin, Germany