nach oben

Intensive Care Medicine

Erschienen in:

01.11.2008 | Review

Immunonutrition in critically ill patients: a systematic review and analysis of the literature

verfasst von: Paul E. Marik, Gary P. Zaloga

Erschienen in: Intensive Care Medicine | Ausgabe 11/2008

Einloggen, um Zugang zu erhalten

Abstract

Background

The role of immuno-modulating diets (IMDs) in critically ill patients is controversial.

Objective

The goal of this meta-analysis was to determine the impact of IMD’s on hospital mortality, nosocomial infections and length of stay (LOS) in critically ill patients. Outcome was stratified according to type of IMD and patient setting.

Data sources

MEDLINE, Embase, Cochrane Register of Controlled Trials.

Study selection

RCT’s that compared the outcome of critically ill patients randomized to an IMD or a control diet.

Data synthesis

Twenty-four studies (with a total of 3013 patients) were included in the meta-analysis; 12 studies included ICU patients, 5 burn patients and 7 trauma patients. Four of the studies used formulas supplemented with arginine, two with arginine and glutamine, nine with arginine and fish oil (FO), two with arginine, glutamine and FO, six with glutamine alone and three studies used a formula supplemented with FO alone. Overall IMD’s had no effect on mortality or LOS, but reduced the number of infections (OR 0.63; 95% CI 0.47–0.86, P = 0.004, I ² = 49%). Mortality, infections and LOS were significantly lower only in the ICU patients receiving the FO IMD (OR 0.42, 95% CI 0.26–0.68; OR 0.45, 95% CI 0.25–0.79 and WMD -6.28 days, 95% CI −9.92 to −2.64, respectively).

Conclusions

An IMD supplemented with FO improved the outcome of medical ICU patients (with SIRS/sepsis/ARDS). IMDs supplemented with arginine with/without additional glutamine or FO do not appear to offer an advantage over standard enteral formulas in ICU, trauma and burn patients.

Marik PE, Zaloga GP (2001) Early enteral nutrition in acutely ill patients: a systematic review. Crit Care Med 29:2264–2270PubMedCrossRef

Artinian V, Krayem H, DiGiovine B (2006) Effects of early enteral feeding on the outcome of critically ill mechanically ventialted medical patients. Chest 129:960–967PubMedCrossRef

Siddiqui RA, Shaikh SR, Sech LA, Yount HR, Stillwell W, Zaloga GP (2004) Omega 3-fatty acids: health benefits and cellular mechanisms of action. Mini Rev Med Chem 4:859–871PubMed

Zaloga GP, Siddiqui RA (2004) Biologically active dietary peptides. Mini Rev Med Chem 4:815–821PubMed

Zaloga GP (1999) Dietary lipids: ancestral ligands and regulators of cell signaling pathways. Crit Care Med 27:1646–1648PubMedCrossRef

Zhou M, Martindale RG (2007) Immune-modulating enteral formulations: optimum components, appropriate patients, and controversial use of arginine in sepsis. Curr Gastroenterol Rep 9:329–337PubMedCrossRef

Wischmeyer PE (2008) Glutamine: role in critical illness and ongoing clinical trials. Curr Opin Gastroenterol 24:190–197PubMedCrossRef

Vermeulen MA, van de Poll MC, Ligthart-Melis GC, Dejong CH, van den Tol MP, Boelens PG, van Leeuwen PA (2007) Specific amino acids in the critically ill patient–exogenous glutamine/arginine: a common denominator? Crit Care Med 35:S568–S576PubMedCrossRef

Mayer K, Seeger W (2008) Fish oil in critical illness. Curr Opin Clin Nutr Metab Care 11:121–127PubMedCrossRef

10.

Montejo JC, Zarazaga A, Lopez-Martinez J, Urrutia G, Roque M, Blesa AL, Celaya S, Conejero R, Galban C, de Garcia LA, Grau T, Mesejo A, Ortiz-Leyba C, Planas M, Ordonez J, Jimenez FJ (2003) Immunonutrition in the intensive care unit. A systematic review and consensus statement. Clin Nutr 22:221–233PubMedCrossRef

11.

Grimble RF (2005) Immunonutrition. Curr Opin Gastroenterol 21:216–222PubMedCrossRef

12.

Alvarez W, Mobarhan S (2003) Finding a place for immunonutrition. Nutr Rev 61:214–218PubMedCrossRef

13.

Curi R, Newsholme P, Procopio J, Lagranha C, Gorjao R, Pithon-Curi TC (2007) Glutamine, gene expression, and cell function. Front Biosci 12:344–357PubMedCrossRef

14.

Calder PC (2007) Immunonutrition in surgical and critically ill patients. Br J Nutr 98(Suppl 1):S133–S139PubMed

15.

Zaloga GP, Siddiqui R, Terry C, Marik PE (2004) Arginine: mediator or modulator of sepsis? Nutr Clin Pract 19:201–215PubMedCrossRef

16.

Wu G, Morris SM Jr (1998) Arginine metabolism: nitric oxide and beyond. Biochem J 336:1–17PubMed

17.

Singleton KD, Beckey VE, Wischmeyer PE (2005) Glutamine prevents activation of NF-kappaB and stress kinase pathways, attenuates inflammatory cytokine release, and prevents acute respiratory distress syndrome (ARDS) following sepsis. Shock 24:583–589PubMedCrossRef

18.

Sato N, Moore FA, Kone BC, Zou L, Smith MA, Childs MA, Moore-Olufemi S, Schultz SG, Kozar RA (2006) Differential induction of PPAR-gamma by luminal glutamine and iNOS by luminal arginine in the rodent postischemic small bowel. Am J Physiol Gastrointest Liver Physiol 290:G616–G623PubMedCrossRef

19.

Melis GC, Ter WN, Boelens PG, van Leeuwen PA (2004) Glutamine: recent developments in research on the clinical significance of glutamine. Curr Opin Clin Nutr Metab Care 7:59–70PubMedCrossRef

20.

Ziegler TR, Ogden LG, Singleton KD, Luo M, Fernandez-Estivariz C, Griffith DP, Galloway JR, Wischmeyer PE (2005) Parenteral glutamine increases serum heat shock protein 70 in critically ill patients. Intensive Care Med 31:1079–1086PubMedCrossRef

21.

Bakalar B, Duska F, Pachl J, Fric M, Otahal M, Pazout J, Andel M (2006) Parenterally administered dipeptide alanyl-glutamine prevents worsening of insulin sensitivity in multiple-trauma patients. Crit Care Med 34:381–386PubMedCrossRef

22.

Zaloga G, Marik P (2001) Lipid modulation and systemic inflammation. Crit Care Clin 17:201–218PubMedCrossRef

23.

Ariel A, Serhan CN (2007) Resolvins and protectins in the termination program of acute inflammation. Trends Immunol 28:176–183PubMedCrossRef

24.

Bansal V, Syres KM, Makarenkova V, Brannon R, Matta B, Harbrecht BG, Ochoa JB (2005) Interactions between fatty acids and arginine metabolism: implications for the design of immune-enhancing diets. JPEN 29:S75–S80

25.

Heyland D, Dhaliwal R (2005) Immunonutrition in the critically ill: from old approaches to new paradigms. Intensive Care Med 31:501–503PubMedCrossRef

26.

Heyland DK, Samis A (2003) Does immunonutrition in patients with sepsis do more harm than good? Intensive Care Med 29:669–671PubMed

27.

Heyland DK, Dhaliwal R, Drover JW, Gramlich L, Dodek P, Canadian critical care clinical practice guidelines committee, Heyland DK, Dhaliwal R, Drover JW, Gramlich L, Dodek P (2003) Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients. JPEN 27:355–373

28.

Heyland DK, Novak F, Drover JW, Jain M, Su X, Suchner U (2001) Should immunonutrition become routine in critically ill patients? A systematic review of the evidence. JAMA 286:944–953PubMedCrossRef

29.

Beale RJ, Bryg DJ, Bihari DJ (1999) Immunonutrition in the critically ill: a systematic review of clinical outcome. Crit Care Med 27:2799–2805PubMedCrossRef

30.

Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF (1999) Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses. Lancet 354:1896–1900PubMedCrossRef

31.

Cochran W (1954) The combination of estimates from different experiments. Biometrics 10:101–129CrossRef

32.

Berlin JA, Laird NM, Sacks HS, Chalmers TC (1989) A comparison of statistical methods for combining event rates from clinical trials. Stat Med 8:141–151PubMedCrossRef

33.

Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558PubMedCrossRef

34.

Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. Br Med J 327:557–560CrossRef

35.

Dent DL, Heyland DK, Levy H, Martindale R, Tayek J, Schloerb P, Kelley MJ (2003) Immunonutrition may increase mortality in critically ill patients with pneumonia: results of a randomized trial. Crit Care Med 30:A17

36.

Brantley S, Pierce J (2000) Effects of enteral nutrition on trauma patients. Nutr Clin Pract 15:S13

37.

Cerra FB, Lehman S, Konstantinides N, Konstantinides F, Shronts EP, Holman R (1990) Effect of enteral nutrient on in vitro tests of immune function in ICU patients: a preliminary report. Nutrition 6:84–87PubMed

38.

Murray JF, Mattay MA, Luce J, Flick M (1988) An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis 138:720–723PubMed

39.

Bower RH, Cerra FB, Bershadsky B, Licari JJ, Hoyt DB, Jensen GL, van Buuren CT, Rothkopf MM, Daly JM, Adelsberg BR (1995) Early enteral administration of a formula (impact) supplemented with arginine, nucleotides, and fish oil in intensive care unit patients: results of a multicenter, prospective, randomized, clinical trial. Crit Care Med 23:436–449PubMedCrossRef

40.

Rodrigo CM, Garcia PJ (1997) THe effect of the composition of the enteral nutrition on infection in the critical patient (Spanish). Nutr Hosp 12:80–84

41.

Atkinson S, Sieffert E, Bihari D (1998) A prospective, randomized, double-blind, controlled clinical trial of enteral immunonutrition in the critically ill. Guy’s Hospital Intensive Care Group. Crit Care Med 26:1164–1172PubMedCrossRef

42.

Gadek JE, DeMichele SJ, Karlstad MD, Pacht ER, Donahoe M, Albertson TE, Van Hoozen C, Wennberg AK, Nelson JL, Noursalehi M (1999) Effect of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in patients with acute respiratory distress syndrome. Enteral Nutrition in ARDS Study Group. Crit Care Med 27:1409–1420PubMedCrossRef

43.

Jones C, Palmer TE, Griffiths RD (1999) Randomized clinical outcome study of critically ill patients given glutamine-supplemented enteral nutrition. Nutrition 15:108–115PubMedCrossRef

44.

Galban C, Montejo JC, Mesejo A, Marco P, Celaya S, Sanchez-Segura JM, Farre M, Bryg DJ (2000) An immune-enhancing enteral diet reduces mortality rate and episodes of bacteremia in septic intensive care unit patients. Crit Care Med 28:643–648PubMedCrossRef

45.

Caparros T, Lopez J, Grau T (2001) Early enteral nutrition in critically ill patients with a high-protein diet enriched with arginine, fiber, and antioxidants compared with a standard high-protein diet. The effect on nosocomial infections and outcome. JPEN 25:299–308

46.

Conejero R, Bonet A, Grau T, Esteban A, Mesejo A, Montejo JC, Lopez J, Acosta JA (2002) Effect of a glutamine-enriched enteral diet on intestinal permeability and infectious morbidity at 28 days in critically ill patients with systemic inflammatory response syndrome: a randomized, single-blind, prospective, multicenter study. Nutrition 18:716–721PubMedCrossRef

47.

Hall JC, Dobb G, Hall J, de Souza R, Brennan L, McCauley R (2003) A prospective randomized trial of enteral glutamine in critical illness. Intensive Care Med 29:1710–1716PubMedCrossRef

48.

Kieft H, Roos AN, van Drunen JD, Bindels AJ, Bindels JG, Hofman Z (2005) Clinical outcome of immunonutrition in a heterogeneous intensive care population. Intensive Care Med 31:524–532PubMedCrossRef

49.

Pontes-Arruda A, Aragao AM, Albuquerque JD (2006) Effects of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in mechanically ventilated patients with severe sepsis and septic shock. Crit Care Med 34:2325–2333PubMedCrossRef

50.

Singer P, Theilla M, Fisher H, Gibsterin L, Grazovoski E, Cohen J (2006) Benefit of an enteral diet enriched with eicosapentaenoic acid and gallm-linolenic acid in ventilated patients with acute lung injury. Crit Care Med 34:1033–1038PubMedCrossRef

51.

Gottschlich MM, Jenkins M, Warden GD, Baumer T, Havens P, Snook JT, Alexander JW (1990) Differential effects of three enteral dietary regimens on selected outcome variables in burn patients. JPEN 14:225–236

52.

Saffle JR, Wiebke G, Jennings K, Morris SE, Barton RG (1997) Randomized trial of immune-enhancing enteral nutrition in burn patients. J Trauma 42:793–800PubMed

53.

Garrel D, Patenaude J, Nedelec B, Samson L, Dorais J, Champoux J, D’Elia M, Bernier J (2003) Decreased mortality and infectious morbidity in adult burn patients given enteral glutamine supplements: a prospective, controlled, randomized clinical trial. Crit Care Med 31:2444–2449PubMedCrossRef

54.

Zhou YP, Jiang ZM, Sun YH, Wang XR, Ma EL, Wilmore D (2003) The effect of supplemental enteral glutamine on plasma levels, gut function, and outcome in severe burns: a randomized, double-blind, controlled clinical trial. JPEN 27:241–245

55.

Wibbenmeyer LA, Mitchell MA, Newel IM, Faucher LD, Amelon MJ, Ruffin TO, Lewis RD, Latenser BA, Kealey PG (2006) Effect of a fish oil and arginine-fortified diet in thermally injured patients. J Burn Care Res 27:694–702PubMedCrossRef

56.

Brown RO, Hunt H, Mowatt-Larssen CA, Wojtysiak SL, Henningfield MF, Kudsk KA (1994) Comparison of specialized and standard enteral formulas in trauma patients. Pharmacotherapy 14:314–320PubMed

57.

Kudsk KA, Minard G, Croce MA, Brown RO, Lowrey TS, Pritchard FE, Dickerson RN, Fabian TC (1996) A randomized trial of isonitrogenous enteral diets after severe trauma. An immune-enhancing diet reduces septic complications. Ann Surg 224:531–540PubMedCrossRef

58.

Mendez C, Jurkovich GJ, Garcia I, Davis D, Parker A, Maier RV (1997) Effects of an immune-enhancing diet in critically injured patients. J Trauma 42:933–940PubMed

59.

Engel JM, Menges T, Neuhauser C, Schaefer B, Hempelmann G (1997) Effects of various feeding regimens in multiple trauma patients on septic complications and immune parameters (German). Anasthesiol Intensivmed Notfallmed Schmerzther 32:234–239PubMed

60.

Weimann A, Bastian L, Bischoff WE, Grotz M, Hansel M, Lotz J, Trautwein C, Tusch G, Schlitt HJ, Regel G (1998) Influence of arginine, omega–3 fatty acids and nucleotide-supplemented enteral support on systemic inflammatory response syndrome and multiple organ failure in patients after severe trauma. Nutrition 14:165–172PubMedCrossRef

61.

Houdijk AP, Rijnsburger ER, Emmy R, Jansen J, Wesdorp RI, Weiss KK, McCamish MA, Teerlink T, Meuwissen SG, Haarman HJ, Thijs LG, van Leeuwen PA (1998) Randomized trial of glutamine-enriched enteral nutrition on infectious morbidity in patients with mutliple trauma. Lancet 352:772–776PubMedCrossRef

62.

Tsuei BJ, Bernard AC, Barksdale AR, Rockich AK, Meier CF, Kearney PA (2005) Supplemental enteral arginine is metabolized to ornithine in injured patients. J Surg Res 123:17–24PubMedCrossRef

63.

Heyland DK, Novak F (2001) Immunonutrition in the critically ill patient: more harm than good? JPEN 25:S51–S55

64.

Heyland DK (2002) Immunonutrition in the critically ill: Putting the cart before the horse? Nutr Clin Pract 17:267–272PubMedCrossRef

65.

Kalil AC, Sevransky JE, Myers DE, Esposito C, Vandivier RW, Eichacker P, Susla GM, Solomon SB, Csako G, Costello R, Sittler KJ, Banks S, Natanson C, Danner RL (2006) Preclinical trial of l-arginine monotherapy alone or with n-acetylcysteine in septic shock. Crit Care Med 34:2719–2728PubMedCrossRef

66.

Marik PE (2003) The cardiovascular dysfunction of sepsis: a NO· and l-arginine deficient state? Crit Care Med 31:971–973PubMedCrossRef

67.

Luiking YC, Poeze M, Dejong CH, Ramsay G, Deutz NE (2004) Sepsis: an arginine deficiency state? Crit Care Med 32:2135–2145PubMedCrossRef

68.

Spain DA, Wilson MA, Garrison RN (1994) Nitric oxide synthase inhibition exacerbates sepsis-induced renal hypoperfusion. Surgery 116:322–330PubMed

69.

Spain DA, Wilson MA, Bar-Natan MF, Garrison RN (1994) Nitric oxide synthase inhibition aggravates intestinal microvascular vasoconstriction and hypoperfusion of bacteremia. J Trauma 36:720–725PubMed

70.

Luiking YC, Poeze M, Hendrikx M (2005) Continuous l-arginine infusion does not deteriorate the hemodynamic condition in patients with severe sepsis. Clin Nutr 24:612–613

71.

Luiking YC, Poeze M, Preiser J (2006) l-arginine infusion in severely septic patients does not enhance protein nitrosylation or haemodynamic instability. e-SPEN 1:14–15

72.

Mancuso P, Whelan J, DeMichele SJ, Snider CC, Guszcza JA, Claycombe KJ, Smith GT, Gregory TJ, Karlstad MD (1997) Effects of eicosapentaenoic and gamma-linolenic acid on lung permeability and alveolar macrophage eicosanoid synthesis in endotoxic rats. Crit Care Med 25:523–532PubMedCrossRef

73.

Pacht ER, DeMichele S, Nelson JL, Hart J, Wennberg AK, Gadek JE (2003) Enteral nutrition with eicosapentaenoic acid, gamma-linolenic acid, and anti-oxidants reduces alveolar inflammatory mediators and protein influx in patients with acute respiratory distress syndrome. Crit Care Med 31:491–500PubMedCrossRef

74.

Deitch EA (1990) Bacterial translocation of the gut flora. J Trauma 30:S184–S189PubMed

75.

Deitch EA (1990) Intestinal permeability is increased in burn patients shortly after injury. Surgery 107:411–416PubMed

76.

Ziegler TR, Smith RJ, O’Dwyer ST, Demling RH, Wilmore DW, Ziegler TR, Smith RJ, O’Dwyer ST, Demling RH, Wilmore DW (1988) Increased intestinal permeability associated with infection in burn patients. Arch Surg 123:1313–1319PubMed

77.

Mainous MR, Tso P, Berg RD, Deitch EA (1991) Studies of the route, magnitude, and time course of bacterial translocation in a model of systemic inflammation. Arch Surg 126:33–37PubMed

78.

Deitch EA (1990) The role of intestinal barrier failure and bacterial translocation in the development of systemic infection and multiple organ failure. Arch Surg 125:403–404PubMed

79.

O’Dwyer ST, Smith RJ, Hwang TL, Wilmore DW (1989) Maintenance of small bowel mucosa with glutamine-enriched parenteral nutrition. JPEN 13:579–585

80.

Wischmeyer PE, Lynch J, Liedel J, Wolfson R, Riehm J, Gottlieb L, Kahana M (2001) Glutamine administration reduces Gram-negative bacteremia in severely burned patients: a prospective, randomized, double-blind trial versus isonitrogenous control. Crit Care Med 29:2075–2080PubMedCrossRef

81.

Gianotti L, Alexander JW, Gennari R, Pyles T, Babcock GF (1995) Oral glutamine decreases bacterial translocation and improves survival in experimental gut-origin sepsis. JPEN 19:69–74

82.

Ameho CK, Adjei AA, Harrison EK, Takeshita K, Morioka T, Arakaki Y, Ito E, Suzuki I, Kulkarni AD, Kawajiri A, Yamamoto S (1997) Prophylactic effect of dietary glutamine supplementation on interleukin 8 and tumour necrosis factor alpha production in trinitrobenzene sulphonic acid induced colitis. Gut 41:487–493PubMedCrossRef

83.

Houdijk AP, van Leeuwen PA, Boermeester MA, Van Lambalgen T, Teerlink T, Flinkerbusch EL, Sauerwein HP, Wesdorp RI (1994) Glutamine-enriched enteral diet increases splanchnic blood flow in the rat. Am J Physiol 267:G1035–G1040PubMed

84.

Jones NE, Heyland DK (2008) Pharmaconutrition: a new emerging paradigm. Curr Opin Gastroenterol 24:215–222PubMedCrossRef

85.

De Jonghe B, Appere-De-Vechi C, Fournier M, Tran B, Merrer J, Melchior JC, Outin H (2001) A prospective survey of nutritional support practices in intensive care unit patients: what is prescribed? What is delivered? Crit Care Med 29:8–12PubMedCrossRef

86.

Strack van Schijndel RJ, Weijs PJ, Koster C, Bissumbhar A, Melis GC, Girbes AR (2007) A closer look at enterally delivered nutrition in the ICU; what you see is not what they get. e-SPEN 2:1–3

87.

Heyland D, Cook DJ, Winder B, Brylowski L, van de Mark H, Guyatt G (1995) Enteral nutrition in the critically ill patient: a prospective survey. Crit Care Med 23:1055–1060PubMedCrossRef

88.

Beale RJ, Sherry T, Lei K, Campbell-Stephen L, McCook J, Smith J, Venetz W, Alteheld B, Stehle P, Schneider H (2008) Early enteral supplementation with key pharmaconutrients improves Sequential Organ Failure Assessment score in critically ill patients with sepsis: outcome of a randomized, controlled, double-blind trial. Crit Care Med 36:131–144PubMedCrossRef

Titel: Immunonutrition in critically ill patients: a systematic review and analysis of the literature
verfasst von: Paul E. Marik
Gary P. Zaloga
Publikationsdatum: 01.11.2008
Verlag: Springer-Verlag
Erschienen in: Intensive Care Medicine / Ausgabe 11/2008
Print ISSN: 0342-4642
Elektronische ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-008-1213-6

Neu im Fachgebiet AINS

23.04.2024 | Appendizitis | Nachrichten

Update AINS

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

hier abonnieren

Springer Medizin

Immunonutrition in critically ill patients: a systematic review and analysis of the literature

Abstract

Background

Objective

Data sources

Study selection

Data synthesis

Conclusions

Neu im Fachgebiet AINS

Hinter dieser Appendizitis steckte ein Erreger

Ärztliche Empathie hilft gegen Rückenschmerzen

Mehr Schaden als Nutzen durch präoperatives Aussetzen von GLP-1-Agonisten?

S3-Leitlinie zu Pankreaskrebs aktualisiert

Update AINS

Springer Medizin

Abstract

Background

Objective

Data sources

Study selection

Data synthesis

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 11/2008

Editors’ comments on a new trial of activated protein C for persistent septic shock

Once is not enough: clinical trials in sepsis

Assessing sedation in critically ill children by bispectral index, auditory-evoked potentials and clinical scales

Image reconstruction affects computer tomographic assessment of lung hyperinflation

Extravascular lung water volume measurement by a novel lithium-thermal indicator dilution method: comparison of three techniques to post-mortem gravimetry

Antithrombin level and circuit thrombosis during hemofiltration after cardiopulmonary bypass

Neu im Fachgebiet AINS

Hinter dieser Appendizitis steckte ein Erreger

Ärztliche Empathie hilft gegen Rückenschmerzen

Mehr Schaden als Nutzen durch präoperatives Aussetzen von GLP-1-Agonisten?

S3-Leitlinie zu Pankreaskrebs aktualisiert

Update AINS