“Young Stroke” Risks Potentially Linked to the Flammer Syndrome Phenotype: Facts and Hypotheses

  • Jiri PolivkaJr
  • Jiri Polivka
  • Martin Pesta
  • Vladimir Rohan
  • Libuse Celedova
  • Rostislav Cevela
  • Ondrej Topolcan
  • Olga GolubnitschajaEmail author
Part of the Advances in Predictive, Preventive and Personalised Medicine book series (APPPM, volume 11)


Currently, the stroke is registered amongst the five leading causes of death and disability worldwide. From the European perspective approximately 1.1 million individuals become stroke diagnosed each year. The disorder demonstrates severe socioeconomic consequences: the associated total EU costs are as high as €45 billion annually.

Even if the majority of the stroke cases are diagnosed in the elderly, about 10% of all patients experience the disorder at the age below 50 years – so-called “young strokes”. Moreover, the incidence as well prevalence of stroke in young adults is dramatically increasing worldwide. Further, the proportion of strokes with unknown etiology among the youngest subgroup of patients reaches up to 39.6–42% that remains largely unexplained. Therefore, specifically modifiable risk factors such as suboptimal heath conditions are proposed to be considered for innovative risk assessment in the “young stroke” prediction and prevention.

Due to symptoms characteristic for the Flammer syndrome (FS), we hypothesised a potential relationship between FS phenotype and increased risks for the “young stroke” predisposition. FS characteristic symptoms and signs analysed in the chapter may further synergistically contribute to the cerebrovascular events being potentially indicative for the stroke predisposition in young individuals.

If the hypothesised association become confirmed by multi-centre studies run, FS phenotype may get of great clinical utility for creating innovative strategies of predictive, preventive and personalised medicine for the stroke management utilising novel screening programmes, individualised patient profiling, specialised questionnaires and novel biomarker patterns for an effective risk assessment, targeted prevention, and therapy monitoring tailored to the person.


Young adults Flammer Syndrome Phenotype Risk factors Individualised patient profile Aetiology Vascular Abnormal BMI Blood flow Microcirculation Life style Sleep patterns Migraine Hormonal regulation Psychology Stress Screening program Questionnaire Risk assessment Baroreceptor sensitivity Cardiac Circadian rhythm Tinnitus Thermoregulation Altered sensation Body dehydration Predictive preventive personalised medicine 


  1. 1.
    Johnston SC, Mendis S, Mathers CD (2009) Global variation in stroke burden and mortality: estimates from monitoring, surveillance, and modelling. Lancet Neurol 8:345–354CrossRefGoogle Scholar
  2. 2.
    Béjot Y, Bailly H, Durier J, Giroud M (2016) Epidemiology of stroke in Europe and trends for the 21st century. Presse Med 45:e391–e398CrossRefGoogle Scholar
  3. 3.
    Polivka J, Polivka J, Rohan V (2018) Predictive and individualized management of stroke—success story in Czech Republic. EPMA J [Internet]. [cited 2018 Nov 26]. Available from: CrossRefGoogle Scholar
  4. 4.
    Maaijwee NAMM, Rutten-Jacobs LCA, Schaapsmeerders P, van Dijk EJ, de Leeuw F-E (2014) Ischaemic stroke in young adults: risk factors and long-term consequences. Nat Rev Neurol 10:315–325CrossRefGoogle Scholar
  5. 5.
    Béjot Y, Delpont B, Giroud M (2016) Rising stroke incidence in young adults: more epidemiological evidence, more questions to be answered. J Am Heart Assoc 5Google Scholar
  6. 6.
    Aigner A, Grittner U, Rolfs A, Norrving B, Siegerink B, Busch MA (2017) Contribution of established stroke risk factors to the burden of stroke in young adults. Stroke 48:1744–1751CrossRefGoogle Scholar
  7. 7.
    von Sarnowski B, Putaala J, Grittner U, Gaertner B, Schminke U, Curtze S et al (2013) Lifestyle risk factors for ischemic stroke and transient ischemic attack in young adults in the Stroke in Young Fabry Patients study. Stroke 44:119–125CrossRefGoogle Scholar
  8. 8.
    Goeggel Simonetti B, Mono M-L, Huynh-Do U, Michel P, Odier C, Sztajzel R et al (2015) Risk factors, aetiology and outcome of ischaemic stroke in young adults: the Swiss Young Stroke Study (SYSS). J Neurol 262:2025–2032CrossRefGoogle Scholar
  9. 9.
    Tatlisumak T, Cucchiara B, Kuroda S, Kasner SE, Putaala J (2018) Nontraumatic intracerebral haemorrhage in young adults. Nat Rev Neurol 14:237–250CrossRefGoogle Scholar
  10. 10.
    Ji R, Schwamm LH, Pervez MA, Singhal AB (2013) Ischemic stroke and transient ischemic attack in young adults: risk factors, diagnostic yield, neuroimaging, and thrombolysis. JAMA Neurol 70:51–57CrossRefGoogle Scholar
  11. 11.
    Kwon SU, Kim JS, Lee JH, Lee MC (2000) Ischemic stroke in Korean young adults. Acta Neurol Scand 101:19–24CrossRefGoogle Scholar
  12. 12.
    de los Ríos F, Kleindorfer DO, Khoury J, Broderick JP, Moomaw CJ, Adeoye O et al (2012) Trends in substance abuse preceding stroke among young adults: a population-based study. Stroke 43:3179–3183CrossRefGoogle Scholar
  13. 13.
    Yesilot Barlas N, Putaala J, Waje-Andreassen U, Vassilopoulou S, Nardi K, Odier C et al (2013) Etiology of first-ever ischaemic stroke in European young adults: the 15 cities young stroke study. Eur J Neurol 20:1431–1439PubMedGoogle Scholar
  14. 14.
    Mallick AA, Ganesan V, Kirkham FJ, Fallon P, Hedderly T, McShane T et al (2014) Childhood arterial ischaemic stroke incidence, presenting features, and risk factors: a prospective population-based study. Lancet Neurol 13:35–43CrossRefGoogle Scholar
  15. 15.
    Gerstl L, Weinberger R, von Kries R, Heinen F, Schroeder AS, Bonfert MV et al (2018) Risk factors in childhood arterial ischaemic stroke: findings from a population-based study in Germany. Eur J Paediatr Neurol 22:380–386CrossRefGoogle Scholar
  16. 16.
    Riel-Romero RMS, Kalra AA, Gonzalez-Toledo E (2009) Childhood and teenage stroke. Neurol Res 31:775–784CrossRefGoogle Scholar
  17. 17.
    Riel-Romero RMS (2008) Neonatal stroke. Neurol Res 30:839–844CrossRefGoogle Scholar
  18. 18.
    Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL et al (1993) Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 24:35–41CrossRefGoogle Scholar
  19. 19.
    Schneider S, Kornejeva A, Vibo R, Kõrv J (2017) Risk factors and etiology of young ischemic stroke patients in Estonia. Stroke Res Treat 2017:8075697PubMedPubMedCentralGoogle Scholar
  20. 20.
    Ferro JM, Massaro AR, Mas J-L (2010) Aetiological diagnosis of ischaemic stroke in young adults. Lancet Neurol 9:1085–1096CrossRefGoogle Scholar
  21. 21.
    Berghöfer A, Pischon T, Reinhold T, Apovian CM, Sharma AM, Willich SN (2008) Obesity prevalence from a European perspective: a systematic review. BMC Public Health 8:200CrossRefGoogle Scholar
  22. 22.
    Wild S, Roglic G, Green A, Sicree R, King H (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27:1047–1053CrossRefGoogle Scholar
  23. 23.
    Wijnhoven TMA, van Raaij JMA, Spinelli A, Rito AI, Hovengen R, Kunesova M et al (2013) WHO European Childhood Obesity Surveillance Initiative 2008: weight, height and body mass index in 6-9-year-old children. Pediatr Obes 8:79–97CrossRefGoogle Scholar
  24. 24.
    O’Donnell MJ, Chin SL, Rangarajan S, Xavier D, Liu L, Zhang H et al (2016) Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study. Lancet 388:761–775CrossRefGoogle Scholar
  25. 25.
    Konieczka K, Ritch R, Traverso CE, Kim DM, Kook MS, Gallino A et al (2014) Flammer syndrome. EPMA J 5:11CrossRefGoogle Scholar
  26. 26.
    Flammer Syndrome [Internet]. [cited 2018 Jul 12]. Available from:
  27. 27.
    Flammer J, Konieczka K (2017) The discovery of the Flammer syndrome: a historical and personal perspective. EPMA J 8:75–97CrossRefGoogle Scholar
  28. 28.
    Konieczka K, Koch S, Binggeli T, Schoetzau A, Kesselring J (2016) Multiple sclerosis and primary vascular dysregulation (Flammer syndrome). EPMA J 7:13PubMedPubMedCentralGoogle Scholar
  29. 29.
    Smokovski I, Risteski M, Polivka J, Zubor P, Konieczka K, Costigliola V et al (2017) Postmenopausal breast cancer: European challenge and innovative concepts. EPMA J 8:159–169CrossRefGoogle Scholar
  30. 30.
    Zubor P, Gondova A, Polivka J, Kasajova P, Konieczka K, Danko J et al (2017) Breast cancer and Flammer syndrome: any symptoms in common for prediction, prevention and personalised medical approach? EPMA J 8:129–140CrossRefGoogle Scholar
  31. 31.
    Bubnov R, Polivka J, Zubor P, Konieczka K, Golubnitschaja O (2017) “Pre-metastatic niches” in breast cancer: are they created by or prior to the tumour onset? “Flammer Syndrome” relevance to address the question. EPMA J 8:141–157CrossRefGoogle Scholar
  32. 32.
    Polivka J, Kralickova M, Polivka J, Kaiser C, Kuhn W, Golubnitschaja O (2017) Mystery of the brain metastatic disease in breast cancer patients: improved patient stratification, disease prediction and targeted prevention on the horizon? EPMA J 8:119–127CrossRefGoogle Scholar
  33. 33.
    Kunin A, Polivka J, Moiseeva N, Golubnitschaja O (2018) “Dry mouth” and “Flammer” syndromes-neglected risks in adolescents and new concepts by predictive, preventive and personalised approach. EPMA J 9:307–317CrossRefGoogle Scholar
  34. 34.
    Barthelmes J, Nägele MP, Ludovici V, Ruschitzka F, Sudano I, Flammer AJ (2017) Endothelial dysfunction in cardiovascular disease and Flammer syndrome-similarities and differences. EPMA J 8:99–109CrossRefGoogle Scholar
  35. 35.
    Gugleta K, Zawinka C, Rickenbacher I, Kochkorov A, Katamay R, Flammer J et al (2006) Analysis of retinal vasodilation after flicker light stimulation in relation to vasospastic propensity. Invest Ophthalmol Vis Sci 47:4034–4041CrossRefGoogle Scholar
  36. 36.
    Donnelly J, Budohoski KP, Smielewski P, Czosnyka M (2016) Regulation of the cerebral circulation: bedside assessment and clinical implications. Crit Care 20:129CrossRefGoogle Scholar
  37. 37.
    Golubnitschaja O (2017) Feeling cold and other underestimated symptoms in breast cancer: anecdotes or individual profiles for advanced patient stratification? EPMA J 8:17–22CrossRefGoogle Scholar
  38. 38.
    Flammer J, Konieczka K, Flammer AJ (2013) The primary vascular dysregulation syndrome: implications for eye diseases. EPMA J 4:14CrossRefGoogle Scholar
  39. 39.
    Konieczka K, Erb C (2017) Diseases potentially related to Flammer syndrome. EPMA J 8:327–332CrossRefGoogle Scholar
  40. 40.
    Wesselink EM, Kappen TH, Torn HM, Slooter AJC, van Klei WA (2018) Intraoperative hypotension and the risk of postoperative adverse outcomes: a systematic review. Br J Anaesth 121:706–721CrossRefGoogle Scholar
  41. 41.
    Golubnitschaja O, Flammer J (2018) Individualised patient profile: clinical utility of Flammer syndrome phenotype and general lessons for predictive, preventive and personalised medicine. EPMA J 9:15–20CrossRefGoogle Scholar
  42. 42.
    Allais G, Chiarle G, Sinigaglia S, Airola G, Schiapparelli P, Benedetto C (2018) Estrogen, migraine, and vascular risk. Neurol Sci 39:11–20CrossRefGoogle Scholar
  43. 43.
    Fridman S, Sposato LA (2018) Migraine with visual aura, incident AF, and stroke risk: is migraine with aura an embolic TIA? Neurology 91:1077–1078CrossRefGoogle Scholar
  44. 44.
    Sen S, Androulakis XM, Duda V, Alonso A, Chen LY, Soliman EZ et al (2018) Migraine with visual aura is a risk factor for incident atrial fibrillation: a cohort study. Neurology 91:e2202–e2210CrossRefGoogle Scholar
  45. 45.
    Sadrameli SS, Gadhia RR, Kabir R, Volpi JJ (2018) Patent foramen ovale in cryptogenic stroke and migraine with aura: does size matter? Cureus 10:e3213PubMedPubMedCentralGoogle Scholar
  46. 46.
    Zhang DP, Li HR, Ma QK, Yin S, Peng YF, Zhang HL et al (2018) Prevalence of stroke and hypoperfusion in patients with isolated vertigo and vascular risk factors. Front Neurol 9:974CrossRefGoogle Scholar
  47. 47.
    Konieczka K, Ritch R, Traverso CE, Kim DM, Kook MS, Gallino A et al (2014) Flammer syndrome. EPMA J 5:11CrossRefGoogle Scholar
  48. 48.
    Huang Y-S, Koo M, Chen J-C, Hwang J-H (2017) The association between tinnitus and the risk of ischemic cerebrovascular disease in young and middle-aged patients: a secondary case-control analysis of a nationwide, population-based health claims database. PLoS One 12:e0187474CrossRefGoogle Scholar
  49. 49.
    Dehkharghani S, Fleischer CC, Qiu D, Yepes M, Tong F (2017) Cerebral temperature dysregulation: MR thermographic monitoring in a nonhuman primate study of acute ischemic stroke. AJNR Am J Neuroradiol 38:712–720CrossRefGoogle Scholar
  50. 50.
    Bahouth MN, Hillis A, Gottesman R (2015) Abstract T MP86: a prospective study of the effect of dehydration on stroke severity and short term outcome. Stroke 46:ATMP86Google Scholar
  51. 51.
    Yong WC, Sanguankeo A, Upala S (2018) Association between primary Sjögren’s syndrome, cardiovascular and cerebrovascular disease: a systematic review and meta-analysis. Clin Exp Rheumatol 36(Suppl 112):190–197PubMedGoogle Scholar
  52. 52.
    Yang D, Qiao L, Zhao LD (2016) Cerebral infarction in a patient with primary Sjogren’s syndrome: a case report and literature review. Beijing Da Xue Xue Bao 48:1077–1080PubMedGoogle Scholar
  53. 53.
    Baban B, Golubnitschaja O (2017) The potential relationship between Flammer and Sjögren syndromes: the chime of dysfunction. EPMA J 8:333–338CrossRefGoogle Scholar
  54. 54.
    Bhaskaran K, Dos-Santos-Silva I, Leon DA, Douglas IJ, Smeeth L (2018) Association of BMI with overall and cause-specific mortality: a population-based cohort study of 3·6 million adults in the UK. Lancet Diabetes Endocrinol 6:944–953CrossRefGoogle Scholar
  55. 55.
    Pache M, Kräuchi K, Cajochen C, Wirz-Justice A, Dubler B, Flammer J et al (2001) Cold feet and prolonged sleep-onset latency in vasospastic syndrome. Lancet 358:125–126CrossRefGoogle Scholar
  56. 56.
    Duss SB, Brill A-K, Bargiotas P, Facchin L, Alexiev F, Manconi M et al (2018) Sleep-wake disorders in stroke-increased stroke risk and deteriorated recovery? An evaluation on the necessity for prevention and treatment. Curr Neurol Neurosci Rep 18:72CrossRefGoogle Scholar
  57. 57.
    Sabel BA, Wang J, Cárdenas-Morales L, Faiq M, Heim C (2018) Mental stress as consequence and cause of vision loss: the dawn of psychosomatic ophthalmology for preventive and personalized medicine. EPMA J 9:133–160CrossRefGoogle Scholar
  58. 58.
    Yeghiazaryan K, Flammer J, Golubnitschaja O (2010) Predictive molecular profiling in blood of healthy vasospastic individuals: clue to targeted prevention as personalised medicine to effective costs. EPMA J 1:263–272CrossRefGoogle Scholar
  59. 59.
    Golubnitschaja O, Yeghiazaryan K, Flammer J (2019) Multiomic signature of glaucoma predisposition in Flammer syndrome affected individuals – innovative PPPM strategies in disease management. Flammer Syndrome and Associated Pathologies. SpringerGoogle Scholar
  60. 60.
    Handforth A, Parker GA (2018) Conditions associated with essential tremor in veterans: a potential role for chronic stress. Tremor Other Hyperkinet Mov (NY) 8:517Google Scholar
  61. 61.
    Gowey MA, Khodneva Y, Tison SE, Carson AP, Cherrington AL, Howard VJ et al (2019) Depressive symptoms, perceived stress, and metabolic health: the REGARDS study. Int J Obes 43:615–632CrossRefGoogle Scholar
  62. 62.
    Leung LY, Caplan LR (2016) Factors associated with delay in presentation to the Hospital for Young Adults with ischemic stroke. Cerebrovasc Dis 42:10–14CrossRefGoogle Scholar
  63. 63.
    Polivka J, Krakorova K, Peterka M, Topolcan O (2016) Current status of biomarker research in neurology. EPMA J 7:14CrossRefGoogle Scholar
  64. 64.
    Polívka J, Rohan V, Sevčík P, Polívka J (2014) Personalized approach to primary and secondary prevention of ischemic stroke. EPMA J 5:9CrossRefGoogle Scholar
  65. 65.
    Rutten-Jacobs LCA, Maaijwee NAM, Arntz RM, Schoonderwaldt HC, Dorresteijn LD, van der Vlugt MJ et al (2013) Long-term risk of recurrent vascular events after young stroke: the FUTURE study. Ann Neurol 74:592–601CrossRefGoogle Scholar
  66. 66.
    Putaala J, Haapaniemi E, Kaste M, Tatlisumak T (2012) How does number of risk factors affect prognosis in young patients with ischemic stroke? Stroke 43:356–361CrossRefGoogle Scholar
  67. 67.
    Li F, Yang L, Yang R, Xu W, Chen F-P, Li N et al (2017) Ischemic stroke in young adults of Northern China: characteristics and risk factors for recurrence. Eur Neurol 77:115–122CrossRefGoogle Scholar
  68. 68.
    Renna R, Pilato F, Profice P, Della Marca G, Broccolini A, Morosetti R et al (2014) Risk factor and etiology analysis of ischemic stroke in young adult patients. J Stroke Cerebrovasc Dis 23:e221–e227CrossRefGoogle Scholar
  69. 69.
    Sarfo FS, Ovbiagele B, Gebregziabher M, Wahab K, Akinyemi R, Akpalu A et al (2018) Stroke among young West Africans: evidence from the SIREN (Stroke Investigative Research and Educational Network) large multisite case-control study. Stroke 49:1116–1122CrossRefGoogle Scholar
  70. 70.
    Montanaro VVA, Freitas DDS, Ruiz MCM, Cavalcanti EBU, Marinho PBC, Freitas MCDNB et al (2017) Ischemic stroke in young adults: profile of SARAH Hospital Brasília from 2008 to 2012. Neurologist 22:61–63CrossRefGoogle Scholar
  71. 71.
    Mitchell AB, Cole JW, McArdle PF, Cheng Y-C, Ryan KA, Sparks MJ et al (2015) Obesity increases risk of ischemic stroke in young adults. Stroke 46:1690–1692CrossRefGoogle Scholar
  72. 72.
    Park D, Lee J-H, Han S (2017) Underweight: another risk factor for cardiovascular disease?: a cross-sectional 2013 Behavioral Risk Factor Surveillance System (BRFSS) study of 491,773 individuals in the USA. Medicine (Baltimore) 96:e8769CrossRefGoogle Scholar
  73. 73.
    Cui R, Iso H, Toyoshima H, Date C, Yamamoto A, Kikuchi S et al (2005) Body mass index and mortality from cardiovascular disease among Japanese men and women: the JACC study. Stroke 36:1377–1382CrossRefGoogle Scholar
  74. 74.
    Markidan J, Cole JW, Cronin CA, Merino JG, Phipps MS, Wozniak MA et al (2018) Smoking and risk of ischemic stroke in young men. Stroke 49:1276–1278CrossRefGoogle Scholar
  75. 75.
    Bhat VM, Cole JW, Sorkin JD, Wozniak MA, Malarcher AM, Giles WH et al (2008) Dose-response relationship between cigarette smoking and risk of ischemic stroke in young women. Stroke 39:2439–2443CrossRefGoogle Scholar
  76. 76.
    Magee CA, Kritharides L, Attia J, McElduff P, Banks E (2012) Short and long sleep duration are associated with prevalent cardiovascular disease in Australian adults. J Sleep Res 21:441–447CrossRefGoogle Scholar
  77. 77.
    Sloan MA, Kittner SJ, Feeser BR, Gardner J, Epstein A, Wozniak MA et al (1998) Illicit drug-associated ischemic stroke in the Baltimore-Washington Young Stroke Study. Neurology 50:1688–1693CrossRefGoogle Scholar
  78. 78.
    Wolff V, Lauer V, Rouyer O, Sellal F, Meyer N, Raul JS et al (2011) Cannabis use, ischemic stroke, and multifocal intracranial vasoconstriction: a prospective study in 48 consecutive young patients. Stroke 42:1778–1780CrossRefGoogle Scholar
  79. 79.
    Westover AN, McBride S, Haley RW (2007) Stroke in young adults who abuse amphetamines or cocaine: a population-based study of hospitalized patients. Arch Gen Psychiatry 64:495–502CrossRefGoogle Scholar
  80. 80.
    Roach REJ, Helmerhorst FM, Lijfering WM, Stijnen T, Algra A, Dekkers OM (2015) Combined oral contraceptives: the risk of myocardial infarction and ischemic stroke. Cochrane Database Syst Rev 8:CD011054Google Scholar
  81. 81.
    Plu-Bureau G, Hugon-Rodin J, Maitrot-Mantelet L, Canonico M (2013) Hormonal contraceptives and arterial disease: an epidemiological update. Best Pract Res Clin Endocrinol Metab 27:35–45CrossRefGoogle Scholar
  82. 82.
    Ban L, Sprigg N, Abdul Sultan A, Nelson-Piercy C, Bath PM, Ludvigsson JF et al (2017) Incidence of first stroke in pregnant and nonpregnant women of childbearing age: a population-based cohort study from England. J Am Heart Assoc 6(4). pii: e004601.Google Scholar
  83. 83.
    Maino A, Siegerink B, Algra A, Martinelli I, Peyvandi F, Rosendaal FR (2016) Pregnancy loss and risk of ischaemic stroke and myocardial infarction. Br J Haematol 174:302–309CrossRefGoogle Scholar
  84. 84.
    González-Gómez FJ, Pérez-Torre P, DeFelipe A, Vera R, Matute C, Cruz-Culebras A et al (2016) Stroke in young adults: incidence rate, risk factors, treatment and prognosis. Rev Clin Esp 216:345–351CrossRefGoogle Scholar
  85. 85.
    Lightbody CE, Clegg A, Patel K, Lucas JC, Storey H, Hackett ML et al (2017) Systematic review and meta-analysis of psychosocial risk factors for stroke. Semin Neurol 37:294–306CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Jiri PolivkaJr
    • 1
    • 2
    • 3
  • Jiri Polivka
    • 3
  • Martin Pesta
    • 2
    • 4
  • Vladimir Rohan
    • 3
  • Libuse Celedova
    • 5
  • Rostislav Cevela
    • 5
  • Ondrej Topolcan
    • 6
  • Olga Golubnitschaja
    • 7
    • 8
    • 9
    Email author
  1. 1.Department of Histology and Embryology, Faculty of Medicine in PilsenCharles UniversityPilsenCzech Republic
  2. 2.Biomedical Centre, Faculty of Medicine in PilsenCharles UniversityPilsenCzech Republic
  3. 3.Department of Neurology, University Hospital Pilsen, and Faculty of Medicine in PilsenCharles UniversityPilsenCzech Republic
  4. 4.Department of Biology, Faculty of Medicine in PilsenCharles UniversityPilsenCzech Republic
  5. 5.Department of Social and Assessment Medicine, Faculty of Medicine in PilsenCharles UniversityPilsenCzech Republic
  6. 6.Department of ImmunochemistryUniversity Hospital PilsenPilsenCzech Republic
  7. 7.Radiological ClinicUKB, Rheinische Friedrich-Wilhelms-Universität BonnBonnGermany
  8. 8.Breast Cancer Research CentreUKB, Rheinische Friedrich-Wilhelms-Universität BonnBonnGermany
  9. 9.Centre for Integrated Oncology, Cologne-BonnRheinische Friedrich-Wilhelms-Universität BonnBonnGermany

Personalised recommendations