{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T05:21:15Z","timestamp":1771305675274,"version":"3.50.1"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100006447","name":"University of Zurich","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006447","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pathologe"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Zusammenfassung<\/jats:title><jats:p>Das Fumarat-Hydratase(FH)-defiziente Nierenzellkarzinom (NZK) ist eine distinkte Entit\u00e4t, welche eine biallelische Inaktivierung des <jats:italic>FH<\/jats:italic>-Gens zeigt, die konsekutiv mit einem Expressions- bzw. Funktionsverlust des FH-Proteins einhergeht. Diese Alteration f\u00fchrt zu einer Akkumulation des Onkometaboliten Fumarat im Citratzyklus und vielf\u00e4ltigen St\u00f6rungen des Zellhaushaltes und der DNA-Prozessierung. Das FH-defiziente NZK zeigt h\u00e4ufig ein morphologisch \u00fcberlappendes Spektrum mit papill\u00e4ren NZK (Typ\u00a02), wobei typischerweise ein Wechsel verschiedener Wachstumsmuster inkl. tubulozystischer, kribriformer und\/oder solider Differenzierung zu beobachten ist. Eine typische, jedoch nicht spezifische morphologische Eigenschaft sind die prominenten eosinophilen, Viruseinschlu\u00dfk\u00f6rperchen-artigen Nukleolen mit perinukleol\u00e4rem Halo. Der immunhistochemische Verlust der FH-Expression untermauert die Diagnose, kann in seltenen F\u00e4llen jedoch erhalten sein. Zumeist zeigen FH-defiziente NZK ein sehr aggressives biologisches Verhalten mit oftmalig prim\u00e4rer Metastasierung bei Diagnosestellung. Die initiale Beschreibung erfolgte als NZK in Assoziation mit dem Heredit\u00e4ren-Leiomyomatose-und-Nierenzellkarzinom(HLRCC)-Syndrom, welches zus\u00e4tzlich kutane und uterine Leiomyome umfasst. Aktuelle Daten zeigen jedoch auch einen steigenden Anteil an sporadischen F\u00e4llen, sodass eine Unterscheidung (heredit\u00e4r vs. sporadisch) angemessen erscheint. Bisher sind wenige, aber vielversprechende Daten bez\u00fcglich wirksamer systemischer therapeutischer Optionen beschrieben. Zusammenfassend ist eine korrekte Diagnose aufgrund des typischerweise biologisch aggressiven Verhaltens, gegebenenfalls vom Standard abweichender therapeutischer Optionen und m\u00f6glichem Indikator einer heredit\u00e4ren Erkrankung von gro\u00dfer Bedeutung.<\/jats:p>","DOI":"10.1007\/s00292-021-00977-y","type":"journal-article","created":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T12:03:02Z","timestamp":1630065782000},"page":"560-564","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Das FH-defiziente Nierenzellkarzinom erweitert das Spektrum der papill\u00e4ren Tumoren in der Niere","FH-deficient renal cell carcinoma expands the spectrum of renal papillary tumors"],"prefix":"10.1007","volume":"42","author":[{"given":"N.","family":"Rupp","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Moch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,8,27]]},"reference":[{"key":"977_CR1","volume-title":"WHO classification of tumours of the urinary system and male genital organs","author":"H Moch","year":"2016","unstructured":"Moch\u00a0H, Humphrey\u00a0P, Ulbright\u00a0T, Reuter\u00a0V (2016) WHO classification of tumours of the urinary system and male genital organs. IARC, Lyon"},{"key":"977_CR2","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1097\/PAS.0000000000000617","volume":"40","author":"K Trpkov","year":"2016","unstructured":"Trpkov\u00a0K, Hes\u00a0O, Agaimy\u00a0A, Bonert\u00a0M, Martinek\u00a0P, Magi-Galluzzi\u00a0C, Kristiansen\u00a0G, L\u00fcders\u00a0C, Nesi\u00a0G, Comp\u00e9rat\u00a0E et al (2016) Fumarate hydratase-deficient renal cell carcinoma is strongly correlated with fumarate hydratase mutation and hereditary leiomyomatosis and renal cell carcinoma syndrome. Am J Surg Pathol 40:865\u2013875. https:\/\/doi.org\/10.1097\/PAS.0000000000000617","journal-title":"Am J Surg Pathol"},{"key":"977_CR3","doi-asserted-by":"publisher","first-page":"3387","DOI":"10.1073\/pnas.051633798","volume":"98","author":"V Launonen","year":"2001","unstructured":"Launonen\u00a0V, Vierimaa\u00a0O, Kiuru\u00a0M, Isola\u00a0J, Roth\u00a0S, Pukkala\u00a0E, Sistonen\u00a0P, Herva\u00a0R, Aaltonen\u00a0LA (2001) Inherited susceptibility to uterine leiomyomas and renal cell cancer. Proc Natl Acad Sci U S\u00a0A 98:3387\u20133392. https:\/\/doi.org\/10.1073\/pnas.051633798","journal-title":"Proc Natl Acad Sci U S A"},{"key":"977_CR4","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1038\/ng849","volume":"30","author":"IPM Tomlinson","year":"2002","unstructured":"Tomlinson\u00a0IPM, Alam\u00a0NA, Rowan\u00a0AJ, Barclay\u00a0E, Jaeger\u00a0EEM, Kelsell\u00a0D, Leigh\u00a0I, Gorman\u00a0P, Lamlum\u00a0H, Rahman\u00a0S et\u00a0al (2002) Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat Genet 30:406\u2013410. https:\/\/doi.org\/10.1038\/ng849","journal-title":"Nat Genet"},{"key":"977_CR5","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1093\/hmg\/ddg148","volume":"12","author":"NA Alam","year":"2003","unstructured":"Alam\u00a0NA, Rowan\u00a0AJ, Wortham\u00a0NC, Pollard\u00a0PJ, Mitchell\u00a0M, Tyrer\u00a0JP, Barclay\u00a0E, Calonje\u00a0E, Manek\u00a0S, Adams\u00a0SJ et\u00a0al (2003) Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency. Hum Mol Genet 12:1241\u20131252. https:\/\/doi.org\/10.1093\/hmg\/ddg148","journal-title":"Hum Mol Genet"},{"key":"977_CR6","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1016\/S0002-9440(10)61757-9","volume":"159","author":"M Kiuru","year":"2001","unstructured":"Kiuru\u00a0M, Launonen\u00a0V, Hietala\u00a0M, Aittom\u00e4ki\u00a0K, Vierimaa\u00a0O, Salovaara\u00a0R, Arola\u00a0J, Pukkala\u00a0E, Sistonen\u00a0P, Herva\u00a0R et al (2001) Familial cutaneous leiomyomatosis is a\u00a0two-hit condition associated with renal cell cancer of characteristic histopathology. Am J Pathol 159:825\u2013829. https:\/\/doi.org\/10.1016\/S0002-9440(10)61757-9","journal-title":"Am J Pathol"},{"key":"977_CR7","doi-asserted-by":"publisher","first-page":"2910","DOI":"10.1158\/1078-0432.CCR-20-4367","volume":"27","author":"JP Gleeson","year":"2021","unstructured":"Gleeson\u00a0JP, Nikolovski\u00a0I, Dinatale\u00a0R, Zucker\u00a0M, Knezevic\u00a0A, Patil\u00a0S, Ged\u00a0Y, Kotecha\u00a0RR, Shapnik\u00a0N, Murray\u00a0S et al (2021) Comprehensive molecular characterization and response to therapy in fumarate hydratase-deficient renal cell carcinoma. Clin Cancer Res 27:2910\u20132919. https:\/\/doi.org\/10.1158\/1078-0432.CCR-20-4367","journal-title":"Clin Cancer Res"},{"key":"977_CR8","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1038\/s41379-018-0017-7","volume":"31","author":"M Muller","year":"2018","unstructured":"Muller\u00a0M, Guillaud-Bataille\u00a0M, Salleron\u00a0J, Genestie\u00a0C, Deveaux\u00a0S, Slama\u00a0A, de Paillerets\u00a0BB, Richard\u00a0S, Benusiglio\u00a0PR, Ferlicot\u00a0S (2018) Pattern multiplicity and fumarate hydratase (FH)\/S-(2-succino)-cysteine (2SC) staining but not eosinophilic nucleoli with perinucleolar halos differentiate hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinomas from kidney tumors without FH gene alteration. Mod Pathol 31:974\u2013983. https:\/\/doi.org\/10.1038\/s41379-018-0017-7","journal-title":"Mod Pathol"},{"key":"977_CR9","first-page":"244","volume":"55","author":"K Pivovar\u010d\u00edkov\u00e1","year":"2019","unstructured":"Pivovar\u010d\u00edkov\u00e1\u00a0K, Mart\u00ednek\u00a0P, Trpkov\u00a0K, Alaghehbandan\u00a0R, Magi-Galluzzi\u00a0C, Mundo\u00a0EC, Berney\u00a0D, Suster\u00a0S, Gill\u00a0A, Rychl\u00fd\u00a0B et al (2019) Fumarate hydratase deficient renal cell carcinoma and fumarate hydratase deficient-like renal cell carcinoma: morphologic comparative study of 23 genetically tested cases. Cesk Patol 55:244\u2013249","journal-title":"Cesk Patol"},{"key":"977_CR10","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1097\/PAS.0000000000000719","volume":"40","author":"SC Smith","year":"2016","unstructured":"Smith\u00a0SC, Trpkov\u00a0K, Chen\u00a0Y\u2011B, Mehra\u00a0R, Sirohi\u00a0D, Ohe\u00a0C, Cani\u00a0AK, Hovelson\u00a0DH, Omata\u00a0K, McHugh\u00a0JB et al (2016) Tubulocystic carcinoma of the kidney with poorly differentiated foci: a frequent morphologic pattern of fumarate hydratase-deficient renal cell carcinoma. Am J Surg Pathol 40:1457\u20131472. https:\/\/doi.org\/10.1097\/PAS.0000000000000719","journal-title":"Am J Surg Pathol"},{"key":"977_CR11","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1097\/PAS.0000000000001000","volume":"42","author":"C Ohe","year":"2018","unstructured":"Ohe\u00a0C, Smith\u00a0SC, Sirohi\u00a0D, Divatia\u00a0M, de Peralta-Venturina\u00a0M, Paner\u00a0GP, Agaimy\u00a0A, Amin\u00a0MB, Argani\u00a0P, Chen\u00a0Y\u2011B et al (2018) Reappraisal of morphologic differences between renal medullary carcinoma, collecting duct carcinoma, and fumarate hydratase-deficient renal cell carcinoma. Am J Surg Pathol 42:279\u2013292. https:\/\/doi.org\/10.1097\/PAS.0000000000001000","journal-title":"Am J Surg Pathol"},{"key":"977_CR12","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1111\/his.13183","volume":"71","author":"SC Smith","year":"2017","unstructured":"Smith\u00a0SC, Sirohi\u00a0D, Ohe\u00a0C, McHugh\u00a0JB, Hornick\u00a0JL, Kalariya\u00a0J, Karia\u00a0S, Snape\u00a0K, Hodgson\u00a0SV, Cani\u00a0AK et al (2017) A distinctive, low-grade oncocytic fumarate hydratase-deficient renal cell carcinoma, morphologically reminiscent of succinate dehydrogenase-deficient renal cell carcinoma. Histopathology 71:42\u201352. https:\/\/doi.org\/10.1111\/his.13183","journal-title":"Histopathology"},{"key":"977_CR13","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1002\/gcc.22878","volume":"59","author":"N Wyvekens","year":"2020","unstructured":"Wyvekens\u00a0N, Valtcheva\u00a0N, Mischo\u00a0A, Helmchen\u00a0B, Hermanns\u00a0T, Choschzick\u00a0M, H\u00f6tker\u00a0AM, Rauch\u00a0A, M\u00fchleisen\u00a0B, Akhoundova\u00a0D et\u00a0al (2020) Novel morphological and genetic features of fumarate hydratase deficient renal cell carcinoma in HLRCC syndrome patients with a\u00a0tailored therapeutic approach. Genes Chromosomes Cancer 59:611\u2013619. https:\/\/doi.org\/10.1002\/gcc.22878","journal-title":"Genes Chromosomes Cancer"},{"key":"977_CR14","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1002\/path.2932","volume":"225","author":"C Bardella","year":"2011","unstructured":"Bardella\u00a0C, El-Bahrawy\u00a0M, Frizzell\u00a0N, Adam\u00a0J, Ternette\u00a0N, Hatipoglu\u00a0E, Howarth\u00a0K, O\u2019Flaherty\u00a0L, Roberts\u00a0I, Turner\u00a0G et al (2011) Aberrant succination of proteins in fumarate hydratase-deficient mice and HLRCC patients is a\u00a0robust biomarker of mutation status. J\u00a0Pathol 225:4\u201311. https:\/\/doi.org\/10.1002\/path.2932","journal-title":"J Pathol"},{"key":"977_CR15","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.semcdb.2019.05.002","volume":"98","author":"C Schmidt","year":"2020","unstructured":"Schmidt\u00a0C, Sciacovelli\u00a0M, Frezza\u00a0C (2020) Fumarate hydratase in cancer: a multifaceted tumour suppressor. Semin Cell Dev Biol 98:15\u201325. https:\/\/doi.org\/10.1016\/j.semcdb.2019.05.002","journal-title":"Semin Cell Dev Biol"},{"key":"977_CR16","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1038\/s41586-020-2363-0","volume":"582","author":"PL Sulkowski","year":"2020","unstructured":"Sulkowski\u00a0PL, Oeck\u00a0S, Dow\u00a0J, Economos\u00a0NG, Mirfakhraie\u00a0L, Liu\u00a0Y, Noronha\u00a0K, Bao\u00a0X, Li\u00a0J, Shuch\u00a0BM et\u00a0al (2020) Oncometabolites suppress DNA repair by disrupting local chromatin signalling. Nature 582:586\u2013591. https:\/\/doi.org\/10.1038\/s41586-020-2363-0","journal-title":"Nature"},{"key":"977_CR17","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.abc4436","author":"DR Crooks","year":"2021","unstructured":"Crooks\u00a0DR, Maio\u00a0N, Lang\u00a0M, Ricketts\u00a0CJ, Vocke\u00a0CD, Gurram\u00a0S, Turan\u00a0S, Kim\u00a0Y\u2011Y, Cawthon\u00a0GM, Sohelian\u00a0F et al (2021) Mitochondrial DNA alterations underlie an irreversible shift to aerobic glycolysis in fumarate hydratase-deficient renal cancer. Sci Signal. https:\/\/doi.org\/10.1126\/scisignal.abc4436","journal-title":"Sci Signal"},{"key":"977_CR18","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.4143\/crt.2019.086","volume":"51","author":"Y Choi","year":"2019","unstructured":"Choi\u00a0Y, Keam\u00a0B, Kim\u00a0M, Yoon\u00a0S, Kim\u00a0D, Choi\u00a0JG, Seo\u00a0JY, Park\u00a0I, Lee\u00a0JL (2019) Bevacizumab plus erlotinib combination therapy for advanced hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinoma: a multicenter retrospective analysis in Korean patients. Cancer Res Treat 51:1549\u20131556. https:\/\/doi.org\/10.4143\/crt.2019.086","journal-title":"Cancer Res Treat"},{"key":"977_CR19","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2020.38.15_suppl.5004","author":"R Srinivasan","year":"2020","unstructured":"Srinivasan\u00a0R, Gurram\u00a0S, Al Harthy\u00a0M, Singer\u00a0EA, Sidana\u00a0A, Shuch\u00a0BM et al (2020) Results from a\u00a0phase II study of bevacizumab and erlotinib in subjects with advanced hereditary leiomyomatosis and renal cell cancer (HLRCC) or sporadic papillary renal cell cancer. J\u00a0Clin Oncol. https:\/\/doi.org\/10.1200\/JCO.2020.38.15_suppl.5004","journal-title":"J\u00a0Clin Oncol"},{"key":"977_CR20","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1002\/gcc.22905","volume":"60","author":"K Garg","year":"2021","unstructured":"Garg\u00a0K, Rabban\u00a0J (2021) Hereditary leiomyomatosis and renal cell carcinoma syndrome associated uterine smooth muscle tumors: bridging morphology and clinical screening. Genes Chromosomes Cancer 60:210\u2013216. https:\/\/doi.org\/10.1002\/gcc.22905","journal-title":"Genes Chromosomes Cancer"},{"key":"977_CR21","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1097\/PAS.0000000000000703","volume":"40","author":"M Miettinen","year":"2016","unstructured":"Miettinen\u00a0M, Felisiak-Golabek\u00a0A, Wasag\u00a0B, Chmara\u00a0M, Wang\u00a0Z, Butzow\u00a0R, Lasota\u00a0J (2016) Fumarase-deficient uterine leiomyomas: an immunohistochemical, molecular genetic, and clinicopathologic study of 86 cases. Am J Surg Pathol 40:1661\u20131669. https:\/\/doi.org\/10.1097\/PAS.0000000000000703","journal-title":"Am J Surg Pathol"},{"key":"977_CR22","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1097\/PAS.0000000000001222","volume":"43","author":"JT Rabban","year":"2019","unstructured":"Rabban\u00a0JT, Chan\u00a0E, Mak\u00a0J, Zaloudek\u00a0C, Garg\u00a0K (2019) Prospective detection of germline mutation of fumarate hydratase in women with uterine smooth muscle tumors using pathology-based screening to trigger genetic counseling for hereditary leiomyomatosis renal cell carcinoma syndrome: a 5\u2011year single institutional experience. Am J Surg Pathol 43:639\u2013655. https:\/\/doi.org\/10.1097\/PAS.0000000000001222","journal-title":"Am J Surg Pathol"},{"key":"977_CR23","doi-asserted-by":"publisher","first-page":"2341","DOI":"10.1038\/s41379-020-0596-y","volume":"33","author":"B Popp","year":"2020","unstructured":"Popp\u00a0B, Erber\u00a0R, Kraus\u00a0C, Vasileiou\u00a0G, Hoyer\u00a0J, Burghaus\u00a0S, Hartmann\u00a0A, Beckmann\u00a0MW, Reis\u00a0A, Agaimy\u00a0A (2020) Targeted sequencing of FH-deficient uterine leiomyomas reveals biallelic inactivating somatic fumarase variants and allows characterization of missense variants. Mod Pathol 33:2341\u20132353. https:\/\/doi.org\/10.1038\/s41379-020-0596-y","journal-title":"Mod Pathol"},{"key":"977_CR24","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1111\/his.14007","volume":"76","author":"C Liu","year":"2020","unstructured":"Liu\u00a0C, Dillon\u00a0J, Beavis\u00a0AL, Liu\u00a0Y, Lombardo\u00a0K, Fader\u00a0AN, Hung\u00a0C\u2011F, Wu\u00a0T\u2011C, Vang\u00a0R, Garcia\u00a0JE et al (2020) Prevalence of somatic and germline mutations of fumarate hydratase in uterine leiomyomas from young patients. Histopathology 76:354\u2013365. https:\/\/doi.org\/10.1111\/his.14007","journal-title":"Histopathology"},{"key":"977_CR25","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1016\/j.euo.2019.11.002","volume":"3","author":"C Forde","year":"2020","unstructured":"Forde\u00a0C, Lim\u00a0DHK, Alwan\u00a0Y, Burghel\u00a0G, Butland\u00a0L, Cleaver\u00a0R, Dixit\u00a0A, Evans\u00a0DG, Hanson\u00a0H, Lalloo\u00a0F et\u00a0al (2020) Hereditary leiomyomatosis and renal cell cancer: clinical, molecular, and screening features in a\u00a0cohort of 185 affected individuals. Eur Urol Oncol 3:764\u2013772. https:\/\/doi.org\/10.1016\/j.euo.2019.11.002","journal-title":"Eur Urol Oncol"},{"key":"977_CR26","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1007\/s10689-014-9735-2","volume":"13","author":"FH Menko","year":"2014","unstructured":"Menko\u00a0FH, Maher\u00a0ER, Schmidt\u00a0LS, Middelton\u00a0LA, Aittom\u00e4ki\u00a0K, Tomlinson\u00a0I, Richard\u00a0S, Linehan\u00a0WM (2014) Hereditary leiomyomatosis and renal cell cancer (HLRCC): renal cancer risk, surveillance and treatment. Fam Cancer 13:637\u2013644. https:\/\/doi.org\/10.1007\/s10689-014-9735-2","journal-title":"Fam Cancer"}],"container-title":["Der Pathologe"],"original-title":[],"language":"de","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00292-021-00977-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00292-021-00977-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00292-021-00977-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T13:07:36Z","timestamp":1634908056000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00292-021-00977-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,27]]},"references-count":26,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["977"],"URL":"https:\/\/doi.org\/10.1007\/s00292-021-00977-y","relation":{},"ISSN":["0172-8113","1432-1963"],"issn-type":[{"value":"0172-8113","type":"print"},{"value":"1432-1963","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,27]]},"assertion":[{"value":"9 July 2021","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 August 2021","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Einhaltung ethischer Richtlinien"}},{"value":"N.\u00a0Rupp gibt eine bezahlte beraterische T\u00e4tigkeit f\u00fcr die F.\u00a0Hoffmann-La Roche AG im Rahmen eines \u201eadvisory boards\u201c an, au\u00dferhalb des Themas des Beitragsinhaltes. H.\u00a0Moch gibt eine T\u00e4tigkeit f\u00fcr die F.\u00a0Hoffmann-La Roche AG, Bayer, Merck, Visiopharm, BMS sowie Johnson und Johnson im Rahmen von \u201eadvisory boards\u201c au\u00dferhalb des Themas des Beitragsinhaltes an.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Interessenkonflikt"}},{"value":"Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren. F\u00fcr die zitierten Arbeiten gelten die jeweiligen dort deklarierten ethischen Richtlinien.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Interessenkonflikt"}}]}}