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Why oral infections matter?

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Jukka H. Meurman
Professor and Physician emeritus
Preses, The Finnish Society of Sciences and Letters
University of Helsinki and Helsinki University Hospital
Department of Oral and Maxillofacial Diseases
Helsinki, Finland

National Academy of Sciences Belarus
May2019

Published in: Healthcare
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Why oral infections matter?

  1. 1. The Finnish Society of Sciences and Letters http://scientiarum.fi/ 27.9.2019 1
  2. 2. 27.9.2019 2 The Finnish Society of Sciences and Letters • The oldest scientific academy in Finland • Established in 1838 • Meets once a month in the House of Estates • Members present their research in public lectures
  3. 3. 27.9.2019 3 The Finnish Society of Sciences and Letters • Gives out Prizes and Awards • Supports research by grants and stipends • Gives statements and scientific expert reports • Advices the government and policymakers in evidence based results • Collaborates with other academies by being member of the Council of Finnish Academies (CoFA)* *CoFA members: The Finnish Society of Sciences and Letters The Finnish Academy of Sciences and Letters The Finnish Academy of Technology The Swedish Academy of Engineering Sciences in Finland
  4. 4. 27.9.2019 4 The Finnish Society of Sciences and Letters Executive Committee Preses Permanent Secretary Office Secretary Representatives of the four Sections • Mathematics and physics • Biosciences • Humanities • Social sciences Yearbook ”Sphinx” and other publications
  5. 5. 27.9.2019 5
  6. 6. 27.9.2019 6 Chair Professor Jukka Meurman Vice Chair Professor Risto Nieminen Members D.Sc. (Tech.) Leni von Bonsdorff Professor Markku Leskelä The Executive Committee of Council of Finnish Academies
  7. 7. www.helsinki.fi/yliopisto Why oral infections matter? Jukka H. Meurman Professor and Physician emeritus Preses, The Finnish Society of Sciences and Letters University of Helsinki and Helsinki University Hospital Department of Oral and Maxillofacial Diseases Helsinki, Finland 27.9.2019Lääke-tieteellinen tiedekunta / J H Meurman / 7 National Academy of Sciences Belarus May 2019
  8. 8. Helsinki University Hospital and Biomedicum Helsinki (Academic Medical Center Helsinki)
  9. 9. 27.9.2019 9 Lääketieteellinen tiedekunta / Henkilön nimi / Esityksen nimi Members of J H Meurman Study Group at the IADR San Francisco meeting 2017
  10. 10. Oral infection and general health Cancer • Oral microbiota and cancer Candida and oral cancer Renal diseases • Pre-dialysis, dialysis, post-transplant state Rheumatic diseases • Immunomodulatory drugs Elderly • non albicans Candida virulence mechanisms Probiotics • Mechanisms of action • Future applications • Novel strains Liver transplant project J H Meurman Study Group Oral microbiology • Endodontal infections and mortality Atheroclerosis • Oral infection and mortality Whatever systemic disease is being investigated, there always seems to be a link to oral infetions Type 2 diabetes Mother/child
  11. 11. Infection Endpoint The paradigm Chronic infection caused inflammatory reaction leads to severe systemic problems Atherosclerosis: CVD, stroke Malignancy Diabetes Pregnancy complications Etc. etc.
  12. 12. Oral infection and mortality Importance of oral infections to health has been known to man more than 3000 years. Modern research has investigated pathomechanisms involved in the association between oral infections and systemic health. 0 0,2 0,4 0,6 0,8 1 1995 1996 1997 1998 1999 No (1) Yes (2) Year Proportion surviving Log-Rank test: Log Rank = 10.52, p = .001 2 (n: 14  4) 1 (n: 79  54) In urgent need of dental treatment Hämäläinen et al. Gerodontology 2004; 21:209-215 The problem is real…
  13. 13. 27.9.2019 13 Lääke-tieteellinen tiedekunta / Henkilön nimi / Esityksen nimi Hämäläinen et al. Oral health and reduction in respiratory capacity in a cohort of community- dwelling elderly people: a population-based 5-year follow-up study. Gerodontology. 2004;21:209-15 CONCLUSION: Periodontal infections and complete prostheses may be reservoirs for pathogens which may be harmful and partly explain the observed reduction in FEV1 during ageing. ? Pneumonia!
  14. 14. Oral infection and general diseases Interaction between oral infection and systemic health was first described in Ancient Egypt. Mandible found in Saqqara dating back 1570 – 1085 B.C. shows two cylindrical holes drilled in bone presumably to relieve pus. ”There is nothing new under the sun”
  15. 15. 15 Oral infection – systemic health Cardiovascular diseases Diabetes Rheumatic diseases Psoriasis Arthritis and other musculoskeletal diseases Renal diseases Liver diseases Autoimmune diseases Geriatric patients Pregancy complications Malignant diseases
  16. 16. Mouth as a source of infections Oral cavity biofilms contain a fairly stable microbiota with potentially pathogenic and opportunistic micro-organisms 1 mg plaque = 1011 bacteria >1000 species
  17. 17. Oral infection – systemic health • Hematogenic spread of oral infections • Bacteremia of oral origin • Medically compromised patients
  18. 18. Dentogenic sepsis treated at the Surgical Hospital in Helsinki
  19. 19. Intensive care unit at the Surgical Hospital, Helsinki University Central Hospital, adjacent to the Department of Oral and Maxillofacial Diseases Life threatening dentogenic infections Intensive care Common ward Periapical osteitis 67% Post-extraction state 28% Pericoronitis 5% Periapical osteitis 71% Post-extraction state 12% Pericoronitis 4% Bone cyst 3% Ylijoki et al. J Oral Maxillofac Surg 2001;59:867
  20. 20. 27.9.2019 20 Helsinki Sudden Death Study 300 acutely died 33-69 year-old men examined post mortem Reason of death OR with 95%CI Significance Coronary thrombosis Heart infarction 7.9 (2.2- 28.6) 3.1 (1.2 – 8.0) P<0.01 P<0.05 Association between unseccussful endodontic treatment with mortality In cases where no signs of periapical lesions were found in the x-rays the endodontic treatment did not link to mortality Karhunen et al. J Dent Res 2006;85:89
  21. 21. Summary relative risk of periodontal disease and coronary heart disease Janket et al. Oral Surg Oral Med Oral Pathol 2003;95:559-569 RR .5 1 1.5 Genco et al. (1997) Beck et al. (1996) Joshipura et al. (1996) Howell et al. (2001) Morrison et al. (1999) Wu et al. (2000a) Mattila et al. (1995) Hujoel et al. (2000) DeStephano et al. (1993) Combined Sok-Ja Janket
  22. 22. 27.9.2019 22 Lääke-tieteellinen tiedekunta / Henkilön nimi / Esityksen nimi JHM & Maha Yakob Explanatory factor Odds ratio Significance Periodontitis High BMI Male gender Low socioeconomic status Porphyromonas gingivalis 4.22 5.78 3.30 4.34 7.63 P<0.05 P<0.0 p<0.05 P<0.05 P<0.01 Yakob et al. J Periodontal Res 2011;46:749 Explanatory factors for increased carotid artery intima media thickness in subjects with and without periodontitis Periodontal disease associates with early signs of atherosclerosis
  23. 23. Janket et al. J Dent Res 2015;94 Suppl:119S-27S The association between oral infections and systemic diseases, such as cardiovascular diseases, can be explained by a variety of mechanisms.
  24. 24. Association of HBA1c with periodontitis in type-2 diabetic patients (Collin et al. J Periodontol 1998;69: 962-6) Poor periodontal status associates significantly with poor glucose metabolic balance in patients with type-2 diabetes Bascones-Martinez et al. Periodontal disease and diabetes. Med Oral Patol Oral Cir Bucal 2011;16:e722-9.
  25. 25. Liver transplant patients • 51 acute liver failure patients • 16 had and 35 did not have dental examination before transplantation • Post-transplant infections recorded and their reasons analyzed • Survival of chirrotic patients analyzed (unpublished) OR (95% CI) No dental screening 2.46 (1.06- 5.69) Helenius et al. Hepatol Res 2014;44:349 Jaana Helenius-Hietala
  26. 26. 27.9.2019 26 Lääke-tieteellinen tiedekunta / Henkilön nimi / Esityksen nimi Steven Offenbacher, published the first studies showing an association between mothers´ poor oral health and adverse pregnancy outcomes. (J Periodontol 1996;67:1103). Misscarriages (Heimonen et al. 2008) Premature (Heimonen et al. 2009) Low birth weight babies Pre-eclampsia Periodontal treatment may reduce adverse pregnancy outcomes (Polyzos et al. 2009)
  27. 27. Assessed for eligibility, 1985, subjects 30 - 40 years in the Stockholm area (n=105,798) Refused to participate (n=1597) Group B Oral clinical examination (n=1676) Group A Periodontal disease (n=286) No periodontal disease (n=1390) Randomized subjects 1594 women and 1679 men (n=3273) Analyzed, 2001 18 Malignant neoplasms 10 Women 8 Men Analyzed, 2001 71 Malignant neoplasms 46 Women 25 Men Drop out study (n=100) Analyzed, 2001 68 Malignant neoplasms 42 Women 26 Men Assessed for eligibility, 1985, subjects 30 - 40 years in the Stockholm area (n=105,798) Assessed for eligibility, 1985, subjects 30 - 40 years in the Stockholm area (n=105,798) Refused to participate (n=1597) Group B Oral clinical examination (n=1676) Group A Periodontal disease (n=286) No periodontal disease (n=1390) Randomized subjects 1594 women and 1679 men (n=3273) Analyzed, 2001 18 Malignant neoplasms 10 Women 8 Men Analyzed, 2001 18 Malignant neoplasms 10 Women 8 Men Analyzed, 2001 71 Malignant neoplasms 46 Women 25 Men Analyzed, 2001 71 Malignant neoplasms 46 Women 25 Men Drop out study (n=100) Drop out study (n=100) Analyzed, 2001 68 Malignant neoplasms 42 Women 26 Men Analyzed, 2001 68 Malignant neoplasms 42 Women 26 Men The Stockholm Study Söder et al. 2010 Chronic periodontitis may associate with malignancies JHM & Maha Yakob 2018 data now available!
  28. 28. CANCER Periodontitis (all) 6% Healthy perio 5% Severe periodontitis 20% Healthy perio 6%*** Dependent variable Explanatory variable Odds ratio 95% confidence interval Female gender 1.79 1.1 - 2.8 CANCER Periodontitis 3.71 1.5 - 8.8 Age 2.31 1.4 – 3.6 The Stockholm Study Söder et al. 2010 Chronic periodontitis may associate with malignancies • 3273 subjects • 30-40 years at baseline. • Cancer incidence registered from 1985 to 2001 Prevalence of periodontitis in cancer patients ***p<0.001 Professors Birgitta and Per-Östen Söder
  29. 29. Dental plaque and cancer Explaining variable Odds ratio with 95% CI P-value Age Male gender Dental plaque 1.98 (1.11-3.54) 1.91 (1.05-3.46) 1.79 (1.01-3.19) 0.022 0.034 0.048 • 1390 randomly selected healthy Swedes • Examined clinically in 1985 • Followed-up to 2009 (Swedish Cancer Registry) Death in cancer Independent variables in multiple regression analysis: age, gender, dental visits, dental plaque, calculus, gingival inflammation, periodontal disease, education, income, socioeconomic status, working status, smoking The Stockholm Study Söder et al. BMJ Open 2012
  30. 30. MECHANISMS OF INFLAMMATION TRIGGERED CARCINOGENESIS Meurman & Bascones-Martinesz 2011. Modified from Chang & Parsonnet Clin Microbiol Rev 2010;23:837 T-cell activation Epithelial cells Recruitment of lymphocytes, neutrophils, macrophages DNA damage TNF-α, IL-6 IL-8, INF-γ, IL-1β, IL-2 ROS RNOS Secretion of CXCL-9, CXCL-10 Increased cell division Mutations Stimulation of B-cells Impaired DNA repair NF-χB P53 tumor suppressor gene Uncontrolled proliferation Chronic inflammation and infection Cancer TNF-α = Tumor necrosis factor alpha IL = Interleukin INF = Interferon ROS = Reactive oxygen species RNOS = Reactive nitrogen oxide species CXCL = C-X-C motif chemokine NF- β = Nuclear factor kappa-light-chain enhancer of β-cells P53 = Tumor suppressor gene
  31. 31. Infection Cancer The paradigm Chronic infection caused inflammatory reaction leads to malignant transformation
  32. 32. Is there evidence of inflammation or of direct infection as the cause of atherothrombotic arterial lesions? C. pneumoniae H. pylori Cytomegalovirus Other lung infections Periodontal infections Smoking Cholesterol Obesity Homocysteine Mental stress Acute exercise Cold exposure CYTOKINE RELEASE (monocytes, lymphocytes) IL1, IL6, TNF- Endothelium, leukocytes Bone Marrow leukocytes, platelets Liver, endothelium Reactant plasma proteins ICAM-1 VCAM-I E-P-selectins CRP, SAA Endothelial dysfunction, lipid deposition, monocyte migration, smooth muscle proliferation Fibrinogen Factor VIII/ VW Tp-A / PAI-I ATHEROSCLEROSIS THROMBOSIS Fibrin D-dimer FDP Mariano Sanz 2005
  33. 33. 27.9.2019 33 Lääke-tieteellinen tiedekunta / Henkilön nimi / Esityksen nimi Research questions • Pathomechanisms explaining the statistical associations between dental infections and systemic diseases? • Is there causality involved? • Does eradication of oral infections lead to amelioration of systemic disease? • What are the special risk groups in this connection? • Are multicentric studies needed?
  34. 34. 27.9.2019 34 Lääketieteellinen tiedekunta / Henkilön nimi / Esityksen nimi IADR/Firenze 2013 – study group IADR gala dinner We need study more…
  35. 35. 27.9.2019 35 Lääke-tieteellinen tiedekunta / Henkilön nimi / Esityksen nimi Thank you!

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