Startseite Gut microbiotas and immune checkpoint inhibitor therapy response: a causal or coincidental relationship?
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Gut microbiotas and immune checkpoint inhibitor therapy response: a causal or coincidental relationship?

  • Sok-Ja Janket , Leland K. Ackerson und Eleftherios P. Diamandis EMAIL logo
Veröffentlicht/Copyright: 17. September 2019
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Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 58 Heft 1

Abstract

As the largest immune organ, human gut microbiome could influence the efficacy of immune checkpoint inhibitor therapy (ICI). However, identifying contributory microbes from over 35,000 species is virtually impossible and the identified microbes are not consistent among studies. The reason for the disparity may be that the microbes found in feces are markers of other factors that link immune response and microbiotas. Notably, gut microbiome is influenced by stool consistency, diet and other lifestyle factors. Therefore, the ICI and microbiotas relationship must be adjusted for potential confounders and analyzed longitudinally. Moreover, a recent study where 11 low-abundance commensal bacteria induced interferon-γ-producing CD8 T cells, challenges the validity of the abundance-oriented microbiotas investigations. This study also confirmed the hierarchy in immunogenic roles among microbiotas. Fecal transplantation trials in germ-free mice provided “the proof of principle” that germ-free mice reproduce the donor’s microbiome and corresponding ICI efficacy. However, species-specific biological differences prevent direct extrapolation between the results in murine and human models. Fecal transplantation or supplementation with microbes found in ICI responders requires caution due to potential adverse events.

Keywords: causal inferences; diet; fecal microbiome; immunotherapy; multi-factorial; probiotics
*Corresponding author: Eleftherios P. Diamandis, MD, PhD, FRCP(C), FRSC, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Clinical Biochemistry, University Health Network, Toronto, ON, Canada; and Head of Clinical Biochemistry, Mount Sinai Hospital and University Health Network, 60 Murray St., Box 32, Floor 6, Rm L6-201, Toronto, ON M5T 3L9, Canada, Phone: (+416) 586-8443

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: Dr. Eleftherios P. Diamandis holds a consultant/advisory role with Abbott Diagnostics. Drs. Sok-Ja Janket and Leland K. Ackerson have nothing to declare.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 2018;359:97–103.10.1126/science.aan4236Suche in Google Scholar

2. Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, Alegre ML, et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science 2018;359:104–8.10.1126/science.aao3290Suche in Google Scholar

3. Routy B, Le Chatelier E, Derosa L, Duong CP, Alou MT, Daillere R, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 2018;359:91–7.10.1126/science.aan3706Suche in Google Scholar

4. Janket SJ, Ackerson LK. What is passing through toll gate 4: lipids or infection? Arch Oral Biol 2015;60:664–6.10.1016/j.archoralbio.2015.01.007Suche in Google Scholar

5. Thaiss CA, Zmora N, Levy M, Elinav E. The microbiome and innate immunity. Nature 2016;535:65–74.10.1038/nature18847Suche in Google Scholar

6. Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 2009;9:313–23.10.1038/nri2515Suche in Google Scholar

7. Foster KR, Schluter J, Coyte KZ, Rakoff-Nahoum S. The evolution of the host microbiome as an ecosystem on a leash. Nature 2017;548:43–51.10.1038/nature23292Suche in Google Scholar

8. Schroder JM, Harder J. Human beta-defensin-2. Int J Biochem Cell Biol 1999;31:645–51.10.1016/S1357-2725(99)00013-8Suche in Google Scholar

9. Geva-Zatorsky N, Sefik E, Kua L, Pasman L, Tan TG, Ortiz-Lopez A, et al. Mining the human gut microbiota for immunomodulatory organisms. Cell 2017;168:928–43.e911.10.1016/j.cell.2017.01.022Suche in Google Scholar PubMed PubMed Central

10. Wang Q, Huang SQ, Li CQ, Xu Q, Zeng QP. Akkermansia muciniphila may determine chondroitin sulfate ameliorating or aggravating osteoarthritis. Front Microbiol 2017;8:1955.10.3389/fmicb.2017.01955Suche in Google Scholar PubMed PubMed Central

11. Chowell D, Morris LG, Grigg CM, Weber JK, Samstein RM, Makarov V, et al. Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy. Science 2018;359:582–7.10.1126/science.aao4572Suche in Google Scholar PubMed PubMed Central

12. Janket SJ, Ackerson LK, Meurman JH. Potential reverse causation? Int J Cancer 2017;140:2168.10.1002/ijc.30624Suche in Google Scholar PubMed

13. Cani PD. Human gut microbiome: hopes, threats and promises. Gut 2018;67:1716–2510.1136/gutjnl-2018-316723Suche in Google Scholar PubMed PubMed Central

14. Munn DH, Mellor AL. Indoleamine 2,3 dioxygenase and metabolic control of immune responses. Trends Immunol 2013;34:137–43.10.1016/j.it.2012.10.001Suche in Google Scholar PubMed PubMed Central

15. Platten M, Wick W, Van den Eynde BJ. Tryptophan catabolism in cancer: beyond IDO and tryptophan depletion. Cancer Res 2012;72:5435–40.10.1158/0008-5472.CAN-12-0569Suche in Google Scholar PubMed

16. Creelan BC, Antonia S, Bepler G, Garrett TJ, Simon GR, Soliman HH. Indoleamine 2,3-dioxygenase activity and clinical outcome following induction chemotherapy and concurrent chemoradiation in stage III non-small cell lung cancer. Oncoimmunology 2013;2:e23428.10.4161/onci.23428Suche in Google Scholar PubMed PubMed Central

17. Huang JY, Butler LM, Midttun O, Ulvik A, Wang R, Jin A. A prospective evaluation of serum kynurenine metabolites and risk of pancreatic cancer. PLoS One 2018;13:e0196465.10.1371/journal.pone.0196465Suche in Google Scholar PubMed PubMed Central

18. Rothschild D, Weissbrod O, Barkan E, Kurilshikov A, Korem T, Zeevi D, et al. Environment dominates over host genetics in shaping human gut microbiota. Nature 2018;555:210–5.10.1038/nature25973Suche in Google Scholar PubMed

19. Gupta VK, Paul S, Dutta C. Geography, Ethnicity or subsistence-specific variations in human microbiome composition and diversity. Front Microbiol 2017;8:1162.10.3389/fmicb.2017.01162Suche in Google Scholar PubMed PubMed Central

20. Falony G, Joossens M, Vieira-Silva S, Wang J, Darzi Y, Faust K, et al. Population-level analysis of gut microbiome variation. Science 2016;352:560–4.10.1126/science.aad3503Suche in Google Scholar PubMed

21. Ericsson AC, Gagliardi J, Bouhan D, Spollen WG, Givan SA, Franklin CL. The influence of caging, bedding, and diet on the composition of the microbiota in different regions of the mouse gut. Sci Rep 2018;8:4065.10.1038/s41598-018-21986-7Suche in Google Scholar PubMed PubMed Central

22. Mestas J, Hughes CC. Of mice and not men: differences between mouse and human immunology. J Immunol 2004;172:2731–8.10.4049/jimmunol.172.5.2731Suche in Google Scholar PubMed

23. Zschaler J, Schlorke D, Arnhold J. Differences in innate immune response between man and mouse. Crit Rev Immunol 2014;34:433–54.10.1615/CritRevImmunol.2014011600Suche in Google Scholar

24. Xu J, Gordon JI. Honor thy symbionts. Proc Natl Acad Sci USA 2003;100:10452–9.10.1073/pnas.1734063100Suche in Google Scholar PubMed PubMed Central

25. Lathrop SK, Bloom SM, Rao SM, Nutsch K, Lio CW, Santacruz N, et al. Peripheral education of the immune system by colonic commensal microbiota. Nature 2011;478:250–4.10.1038/nature10434Suche in Google Scholar PubMed PubMed Central

26. Hanage WP. Microbiology: microbiome science needs a healthy dose of scepticism. Nature 2014;512:247–8.10.1038/512247aSuche in Google Scholar PubMed

27. Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 2011;472:57–63.10.1038/nature09922Suche in Google Scholar PubMed PubMed Central

28. Gregory JC, Buffa JA, Org E, Wang Z, Levison BS, Zhu W, et al. Transmission of atherosclerosis susceptibility with gut microbial transplantation. J Bio Chem 2015;290:5647–60.10.1074/jbc.M114.618249Suche in Google Scholar PubMed PubMed Central

29. Yin J, Liao SX, He Y, Wang S, Xia GH, Liu FT, et al. Dysbiosis of gut microbiota with reduced trimethylamine-N-oxide level in patients with large-artery atherosclerotic stroke or transient ischemic attack. J Am Heart Assoc 2015;4:e002699.10.1161/JAHA.115.002699Suche in Google Scholar PubMed PubMed Central

30. Carvalho BM, Guadagnini D, Tsukumo DM, Schenka AA, Latuf-Filho P, Vassallo J, et al. Modulation of gut microbiota by antibiotics improves insulin signalling in high-fat fed mice. Diabetologia 2012;55:2823–34.10.1007/s00125-012-2648-4Suche in Google Scholar PubMed

31. Reijnders D, Goossens GH, Hermes GD, Neis EP, van der Beek CM, Most J, et al. Effects of gut microbiota manipulation by antibiotics on host metabolism in obese humans: a randomized double-blind placebo-controlled trial. Cell Metab 2016;24:63–74.10.1016/j.cmet.2016.06.016Suche in Google Scholar PubMed

32. Cavenee WK, Dryja TP, Phillips RA, Benedict WF, Godbout R, Gallie BL, et al. Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. Nature 1983;305:779–84.10.1038/305779a0Suche in Google Scholar PubMed

33. Vooijs M, Berns A. Developmental defects and tumor predisposition in Rb mutant mice. Oncogene 1999;18:5293–303.10.1038/sj.onc.1202999Suche in Google Scholar PubMed

34. Passamano L, Taglia A, Palladino A, Viggiano E, D’Ambrosio P, Scutifero M, et al. Improvement of survival in Duchenne Muscular Dystrophy: retrospective analysis of 835 patients. Acta Myol 2012;31:121–5.Suche in Google Scholar

35. McGreevy JW, Hakim CH, McIntosh MA, Duan D. Animal models of Duchenne muscular dystrophy: from basic mechanisms to gene therapy. Dis Models Mech 2015;8:195–213.10.1242/dmm.018424Suche in Google Scholar PubMed PubMed Central

36. Samuel BS, Shaito A, Motoike T, Rey FE, Backhed F, Manchester JK, et al. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Nat Acad Sci USA 2008;105:16767–72.10.1073/pnas.0808567105Suche in Google Scholar PubMed PubMed Central

37. Dewulf EM, Ge Q, Bindels LB, Sohet FM, Cani PD, Brichard SM, et al. Evaluation of the relationship between GPR43 and adiposity in human. Nutr Metab (Lond) 2013;10:11.10.1186/1743-7075-10-11Suche in Google Scholar PubMed PubMed Central

38. Gibbons DL, Spencer J. Mouse and human intestinal immunity: same ballpark, different players; different rules, same score. Mucosal Immunol 2011;4:148–57.10.1038/mi.2010.85Suche in Google Scholar PubMed

39. Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV, Xu W, et al. Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Nat Acad Sci USA 2013;110:3507–12.10.1073/pnas.1222878110Suche in Google Scholar PubMed PubMed Central

40. Ang Z, Ding JL. GPR41 and GPR43 in obesity and inflammation – protective or causative? Front Immunol 2016;7:28.10.3389/fimmu.2016.00028Suche in Google Scholar PubMed PubMed Central

41. Heinsen FA, Knecht H, Neulinger SC, Schmitz RA, Knecht C, Kuhbacher T, et al. Dynamic changes of the luminal and mucosa-associated gut microbiota during and after antibiotic therapy with paromomycin. Gut Microbes 2015;6:243–54.10.1080/19490976.2015.1062959Suche in Google Scholar PubMed PubMed Central

42. Marteau P, Pochart P, Dore J, Bera-Maillet C, Bernalier A, Corthier G. Comparative study of bacterial groups within the human cecal and fecal microbiota. Appl Environ Microbiol 2001;67:4939–42.10.1128/AEM.67.10.4939-4942.2001Suche in Google Scholar PubMed PubMed Central

43. Janket S, Nunn ME, Salih E, Baird AE. Evidence-based approach in transaltional dental research. In: Meurman JH, editor. Translational oral health research. Berlin, Germany: Springer, 2018.10.1007/978-3-319-78205-8_8Suche in Google Scholar

44. Romano-Keeler J, Moore DJ, Wang C, Brucker RM, Fonnesbeck C, Slaughter JC, et al. Early life establishment of site-specific microbial communities in the gut. Gut Microbes 2014;5: 192–201.10.4161/gmic.28442Suche in Google Scholar PubMed PubMed Central

45. Falony G, Vieira-Silva S, Raes J. Richness and ecosystem development across faecal snapshots of the gut microbiota. Nat Microbiol 2018;3:526–8.10.1038/s41564-018-0143-5Suche in Google Scholar PubMed

46. Bressa C, Bailen-Andrino M, Perez-Santiago J, Gonzalez-Soltero R, Perez M, Montalvo-Lominchar MG, et al. Differences in gut microbiota profile between women with active lifestyle and sedentary women. PLoS One 2017;12:e0171352.10.1371/journal.pone.0171352Suche in Google Scholar PubMed PubMed Central

47. Aggarwal BB, Vijayalekshmi RV, Sung B. Targeting inflammatory pathways for prevention and therapy of cancer: short-term friend, long-term foe. Clin Cancer Res 2009;15:425–30.10.1158/1078-0432.CCR-08-0149Suche in Google Scholar PubMed

48. Patyar S, Joshi R, Byrav DS, Prakash A, Medhi B, Das BK. Bacteria in cancer therapy: a novel experimental strategy. J Biomed Sci 2010;17:21.10.1186/1423-0127-17-21Suche in Google Scholar PubMed PubMed Central

49. Minton NP. Clostridia in cancer therapy. Nat Rev Microbiol 2003;1:237–42.10.1002/3527600108.ch8Suche in Google Scholar

50. Riviere A, Selak M, Lantin D, Leroy F, De Vuyst L. Bifidobacteria and butyrate-producing colon bacteria: importance and strategies for their stimulation in the human gut. Front Microbiol 2016;7:979.10.3389/fmicb.2016.00979Suche in Google Scholar PubMed PubMed Central

51. Duncan SH, Louis P, Thomson JM, Flint HJ. The role of pH in determining the species composition of the human colonic microbiota. Environ Microbiol 2009;11:2112–22.10.1111/j.1462-2920.2009.01931.xSuche in Google Scholar PubMed

52. Van Herreweghen F, De Paepe K, Roume H, Kerckhof FM, Van de Wiele T. Mucin degradation niche as a driver of microbiome composition and Akkermansia muciniphila abundance in a dynamic gut model is donor independent. FEMS Microbiol Ecol 2018;94:1–13.10.1093/femsec/fiy186Suche in Google Scholar PubMed

53. Derrien M, Vaughan EE, Plugge CM, de Vos WM. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int J Syst Evol Microbiol 2004;54:1469–76.10.1099/ijs.0.02873-0Suche in Google Scholar

54. Desai MS, Seekatz AM, Koropatkin NM, Kamada N, Hickey CA, Wolter M, et al. A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell 2016;167:1339–53.10.1016/j.cell.2016.10.043Suche in Google Scholar

55. David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 2014;505:559–63.10.1038/nature12820Suche in Google Scholar

56. Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science 2011;334:105–8.10.1126/science.1208344Suche in Google Scholar

57. Tanoue T, Morita S, Plichta DR, Skelly AN, Suda W, Sugiura Y, et al. A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. Nature 2019;565:600–5.10.1038/s41586-019-0878-zSuche in Google Scholar

58. Chitapanarux I, Chitapanarux T, Traisathit P, Kudumpee S, Tharavichitkul E, Lorvidhaya V. Randomized controlled trial of live lactobacillus acidophilus plus bifidobacterium bifidum in prophylaxis of diarrhea during radiotherapy in cervical cancer patients. Radiat Oncol 2010;5:31.10.1186/1748-717X-5-31Suche in Google Scholar

59. Wada M, Nagata S, Saito M, Shimizu T, Yamashiro Y, Matsuki T, et al. Effects of the enteral administration of Bifidobacterium breve on patients undergoing chemotherapy for pediatric malignancies. Support Care Cancer 2010;18:751–9.10.1007/s00520-009-0711-6Suche in Google Scholar

60. Allen SJ, Wareham K, Wang D, Bradley C, Hutchings H, Harris W, et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2013;382:1249–57.10.1016/S0140-6736(13)61218-0Suche in Google Scholar

61. Freedman SB, Williamson-Urquhart S, Farion KJ, Gouin S, Willan AR, Poonai N, et al. Multicenter trial of a combination probiotic for children with gastroenteritis. N Engl J Med 2018;379:2015–26.10.1056/NEJMoa1802597Suche in Google Scholar PubMed

62. Schnadower D, Tarr PI, Casper TC, Gorelick MH, Dean JM, O’Connell KJ, et al. Lactobacillus rhamnosus GG versus placebo for acute gastroenteritis in children. N Engl J Med 2018;379:2002–14.10.1056/NEJMoa1802598Suche in Google Scholar PubMed PubMed Central

63. Worthley DL, Le Leu RK, Whitehall VL, Conlon M, Christophersen C, Belobrajdic D, et al. A human, double-blind, placebo-controlled, crossover trial of prebiotic, probiotic, and synbiotic supplementation: effects on luminal, inflammatory, epigenetic, and epithelial biomarkers of colorectal cancer. Am J Clin Nutr 2009;90:578–86.10.3945/ajcn.2009.28106Suche in Google Scholar

64. Besselink MG, van Santvoort HC, Buskens E, Boermeester MA, van Goor H, Timmerman HM, et al. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet 2008;371:651–9.10.1016/S0140-6736(08)60207-XSuche in Google Scholar

65. Bafeta A, Koh M, Riveros C, Ravaud P. Harms reporting in randomized controlled trials of interventions aimed at modifying microbiota: a systematic review. Ann Intern Med 2018;169:240–7.10.7326/M18-0343Suche in Google Scholar

66. Abbasi J. Are probiotics money down the toilet? or worse? J Am Med Assoc 2019;321(7):633–5.10.1001/jama.2018.20798Suche in Google Scholar

67. Harty DW, Oakey HJ, Patrikakis M, Hume EB, Knox KW. Pathogenic potential of lactobacilli. Int J Food Microbiol 1994;24:179–89.10.1016/0168-1605(94)90117-1Suche in Google Scholar

68. Husni RN, Gordon SM, Washington JA, Longworth DL. Lactobacillus bacteremia and endocarditis: review of 45 cases. Clin Infect Dis 1997;25:1048–55.10.1086/516109Suche in Google Scholar PubMed

69. Salminen MK, Rautelin H, Tynkkynen S, Poussa T, Saxelin M, Valtonen V, et al. Lactobacillus bacteremia, clinical significance, and patient outcome, with special focus on probiotic L. rhamnosus GG. Clin Infect Dis 2004;38:62–9.10.1086/380455Suche in Google Scholar PubMed

70. Lee MR, Tsai CJ, Liang SK, Lin CK, Huang YT, Hsueh PR. Clinical characteristics of bacteraemia caused by Lactobacillus spp. and antimicrobial susceptibilities of the isolates at a medical centre in Taiwan, 2000–2014. Int J Antimicrob Agents 2015;46:439–45.10.1016/j.ijantimicag.2015.06.017Suche in Google Scholar PubMed

71. Janket SJ, Javaheri H, Ackerson LK, Ayilavarapu S, Meurman JH. Oral infections, metabolic inflammation, genetics, and cardiometabolic diseases. J Dent Res 2015;94:119s–27s.10.1177/0022034515580795Suche in Google Scholar PubMed

72. Dai C, Jiang M, Sun MJ. The safety of probiotics in IBS and CIC is worthy of further discussion. Am J Gastroenterol 2014;109:1838–9.10.1038/ajg.2014.304Suche in Google Scholar PubMed

73. Didari T, Solki S, Mozaffari S, Nikfar S, Abdollahi M. A systematic review of the safety of probiotics. Expert Opin Drug Saf 2014;13:227–39.10.1517/14740338.2014.872627Suche in Google Scholar PubMed

74. Wang S, Xu M, Wang W, Cao X, Piao M, Khan S, et al. Systematic review: adverse events of fecal microbiota transplantation. PLoS One 2016;11:e0161174.10.1371/journal.pone.0161174Suche in Google Scholar PubMed PubMed Central

75. De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart S, et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci USA 2010;107:14691–6.10.1073/pnas.1005963107Suche in Google Scholar PubMed PubMed Central

Article note

An excerpt from this commentary has been presented at the 45th International Society of Oncology and Biomarkers, in Hamburg, Germany on November 25th, 2018.

Received: 2019-06-14
Accepted: 2019-08-06
Published Online: 2019-09-17
Published in Print: 2019-12-18

©2020 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Reflex TSH strategy: the good, the bad and the ugly
  4. Review
  5. Shortcomings in the evaluation of biomarkers in ovarian cancer: a systematic review
  6. Mini Review
  7. Clinical application of presepsin as diagnostic biomarker of infection: overview and updates
  8. Opinion Paper
  9. Gut microbiotas and immune checkpoint inhibitor therapy response: a causal or coincidental relationship?
  10. EFLM Paper
  11. Systematic review and meta-analysis of within-subject and between-subject biological variation estimates of 20 haematological parameters
  12. General Clinical Chemistry and Laboratory Medicine
  13. Pre-, post- or no acidification of urine samples for calcium analysis: does it matter?
  14. Pre-analytical and analytical confounders of serum calprotectin as a biomarker in rheumatoid arthritis
  15. Dynamics of soluble syndecan-1 in maternal serum during and after pregnancies complicated by preeclampsia: a nested case control study
  16. Multi-site performance evaluation and Sigma metrics of 20 assays on the Atellica chemistry and immunoassay analyzers
  17. Plasma creatinine medians from patients partitioned by gender and age used as a tool for assessment of analytical stability at different concentrations
  18. Two-center comparison of 10 fully-automated commercial procalcitonin (PCT) immunoassays
  19. Method comparison of four clinically available assays for serum free light chain analysis
  20. Comparison of three different chemiluminescence assays and a rapid liquid chromatography tandem mass spectrometry method for measuring serum aldosterone
  21. Repeatability and reproducibility of lipoprotein particle profile measurements in plasma samples by ultracentrifugation
  22. Reference Values and Biological Variations
  23. A study on reference interval transference via linear regression
  24. Cancer Diagnostics
  25. Unstimulated high-sensitive thyroglobulin is a powerful prognostic predictor in patients with thyroid cancer
  26. Cardiovascular Diseases
  27. Analytical validation of a highly sensitive point-of-care system for cardiac troponin I determination
  28. Acknowledgment
  29. Letters to the Editor
  30. Are icteric and lipemic indices reliable to screen for hyperbilirubinemia and hypertriglyceridemia?
  31. Anti-streptavidin antibodies as a cause of false-positive results of streptavidin-based autoantibody assays
  32. Assessment of complement interference in anti-Müllerian hormone immunoassays
  33. Validating thyroid-stimulating hormone (TSH) reflexive testing cutpoints in a tertiary care institution
  34. Results of the second external quality assessment for human papillomavirus genotyping in Shanghai, China
  35. Development of suitable external quality control material for G6PD deficiency screening with the fluorescent spot test
  36. Non-linearity in commercially available lipase assays: still gaps to close
  37. JAK2, 46/1 haplotype and chronic myelogenous leukemia: diagnostic and therapeutic potential
  38. Congress Abstracts
  39. 11th National Scientifc Congress SPML
https://doi.org/10.1515/cclm-2019-0605
Schlagwörter für diesen Artikel
causal inferences; diet; fecal microbiome; immunotherapy; multi-factorial; probiotics

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Reflex TSH strategy: the good, the bad and the ugly
  4. Review
  5. Shortcomings in the evaluation of biomarkers in ovarian cancer: a systematic review
  6. Mini Review
  7. Clinical application of presepsin as diagnostic biomarker of infection: overview and updates
  8. Opinion Paper
  9. Gut microbiotas and immune checkpoint inhibitor therapy response: a causal or coincidental relationship?
  10. EFLM Paper
  11. Systematic review and meta-analysis of within-subject and between-subject biological variation estimates of 20 haematological parameters
  12. General Clinical Chemistry and Laboratory Medicine
  13. Pre-, post- or no acidification of urine samples for calcium analysis: does it matter?
  14. Pre-analytical and analytical confounders of serum calprotectin as a biomarker in rheumatoid arthritis
  15. Dynamics of soluble syndecan-1 in maternal serum during and after pregnancies complicated by preeclampsia: a nested case control study
  16. Multi-site performance evaluation and Sigma metrics of 20 assays on the Atellica chemistry and immunoassay analyzers
  17. Plasma creatinine medians from patients partitioned by gender and age used as a tool for assessment of analytical stability at different concentrations
  18. Two-center comparison of 10 fully-automated commercial procalcitonin (PCT) immunoassays
  19. Method comparison of four clinically available assays for serum free light chain analysis
  20. Comparison of three different chemiluminescence assays and a rapid liquid chromatography tandem mass spectrometry method for measuring serum aldosterone
  21. Repeatability and reproducibility of lipoprotein particle profile measurements in plasma samples by ultracentrifugation
  22. Reference Values and Biological Variations
  23. A study on reference interval transference via linear regression
  24. Cancer Diagnostics
  25. Unstimulated high-sensitive thyroglobulin is a powerful prognostic predictor in patients with thyroid cancer
  26. Cardiovascular Diseases
  27. Analytical validation of a highly sensitive point-of-care system for cardiac troponin I determination
  28. Acknowledgment
  29. Letters to the Editor
  30. Are icteric and lipemic indices reliable to screen for hyperbilirubinemia and hypertriglyceridemia?
  31. Anti-streptavidin antibodies as a cause of false-positive results of streptavidin-based autoantibody assays
  32. Assessment of complement interference in anti-Müllerian hormone immunoassays
  33. Validating thyroid-stimulating hormone (TSH) reflexive testing cutpoints in a tertiary care institution
  34. Results of the second external quality assessment for human papillomavirus genotyping in Shanghai, China
  35. Development of suitable external quality control material for G6PD deficiency screening with the fluorescent spot test
  36. Non-linearity in commercially available lipase assays: still gaps to close
  37. JAK2, 46/1 haplotype and chronic myelogenous leukemia: diagnostic and therapeutic potential
  38. Congress Abstracts
  39. 11th National Scientifc Congress SPML
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