TY - JOUR
A1 - Ferreira, Manuel A.
A1 - Gamazon, Eric R.
A1 - Al-Ejeh, Fares
A1 - Aittomäki, Kristiina
A1 - Andrulis, Irene L.
A1 - Anton-Culver, Hoda
A1 - Arason, Adalgeir
A1 - Arndt, Volker
A1 - Aronson, Kristan J.
A1 - Arun, Banu K.
A1 - Asseryanis, Ella
A1 - Azzollini, Jacopo
A1 - Balmaña, Judith
A1 - Barnes, Daniel R.
A1 - Barrowdale, Daniel
A1 - Beckmann, Matthias W.
A1 - Behrens, Sabine
A1 - Benitez, Javier
A1 - Bermisheva, Marina
A1 - Bialkowska, Katarzyna
A1 - Blomqvist, Carl
A1 - Bogdanova, Natalia V.
A1 - Bojesen, Stig E.
A1 - Bolla, Manjeet K.
A1 - Borg, Ake
A1 - Brauch, Hiltrud
A1 - Brenner, Hermann
A1 - Broeks, Annegien
A1 - Burwinkel, Barbara
A1 - Caldés, Trinidad
A1 - Caligo, Maria A.
A1 - Campa, Daniele
A1 - Campbell, Ian
A1 - Canzian, Federico
A1 - Carter, Jonathan
A1 - Carter, Brian D.
A1 - Castelao, Jose E.
A1 - Chang-Claude, Jenny
A1 - Chanock, Stephen J.
A1 - Christiansen, Hans
A1 - Chung, Wendy K.
A1 - Claes, Kathleen B. M.
A1 - Clarke, Christine L.
A1 - Couch, Fergus J.
A1 - Cox, Angela
A1 - Cross, Simon S.
A1 - Czene, Kamila
A1 - Daly, Mary B.
A1 - de la Hoya, Miguel
A1 - Dennis, Joe
A1 - Devilee, Peter
A1 - Diez, Orland
A1 - Dörk, Thilo
A1 - Dunning, Alison M.
A1 - Dwek, Miriam
A1 - Eccles, Diana M.
A1 - Ejlertsen, Bent
A1 - Ellberg, Carolina
A1 - Engel, Christoph
A1 - Eriksson, Mikael
A1 - Fasching, Peter A.
A1 - Fletcher, Olivia
A1 - Flyger, Henrik
A1 - Friedman, Eitan
A1 - Frost, Debra
A1 - Gabrielson, Marike
A1 - Gago-Dominguez, Manuela
A1 - Ganz, Patricia A.
A1 - Gapstur, Susan M.
A1 - Garber, Judy
A1 - García-Closas, Montserrat
A1 - García-Sáenz, José A.
A1 - Gaudet, Mia M.
A1 - Giles, Graham G.
A1 - Glendon, Gord
A1 - Godwin, Andrew K.
A1 - Goldberg, Mark S.
A1 - Goldgar, David E.
A1 - González-Neira, Anna
A1 - Greene, Mark H.
A1 - Gronwald, Jacek
A1 - Guenél, Pascal
A1 - Haimann, Christopher A.
A1 - Hall, Per
A1 - Hamann, Ute
A1 - He, Wei
A1 - Heyworth, Jane
A1 - Hogervorst, Frans B. L.
A1 - Hollestelle, Antoinette
A1 - Hoover, Robert N.
A1 - Hopper, John L.
A1 - Hulick, Peter J.
A1 - Humphreys, Keith
A1 - Imyanitov, Evgeny N.
A1 - Isaacs, Claudine
A1 - Jakimovska, Milena
A1 - Jakubowska, Anna
A1 - James, Paul A.
A1 - Janavicius, Ramunas
A1 - Jankowitz, Rachel C.
A1 - John, Esther M.
A1 - Johnson, Nichola
A1 - Joseph, Vijai
A1 - Karlan, Beth Y.
A1 - Khusnutdinova, Elza
A1 - Kiiski, Johanna I.
A1 - Ko, Yon-Dschun
A1 - Jones, Michael E.
A1 - Konstantopoulou, Irene
A1 - Kristensen, Vessela N.
A1 - Laitman, Yael
A1 - Lambrechts, Diether
A1 - Lazaro, Conxi
A1 - Leslie, Goska
A1 - Lester, Jenny
A1 - Lesueur, Fabienne
A1 - Lindström, Sara
A1 - Long, Jirong
A1 - Loud, Jennifer T.
A1 - Lubiński, Jan
A1 - Makalic, Enes
A1 - Mannermaa, Arto
A1 - Manoochehri, Mehdi
A1 - Margolin, Sara
A1 - Maurer, Tabea
A1 - Mavroudis, Dimitrios
A1 - McGuffog, Lesley
A1 - Meindl, Alfons
A1 - Menon, Usha
A1 - Michailidou, Kyriaki
A1 - Miller, Austin
A1 - Montagna, Marco
A1 - Moreno, Fernando
A1 - Moserle, Lidia
A1 - Mulligan, Anna Marie
A1 - Nathanson, Katherine L.
A1 - Neuhausen, Susan L.
A1 - Nevanlinna, Heli
A1 - Nevelsteen, Ines
A1 - Nielsen, Finn C.
A1 - Nikitina-Zake, Liene
A1 - Nussbaum, Robert L.
A1 - Offit, Kenneth
A1 - Olah, Edith
A1 - Olopade, Olufunmilayo I.
A1 - Olsson, Håkan
A1 - Osorio, Ana
A1 - Papp, Janos
A1 - Park-Simon, Tjoung-Won
A1 - Parsons, Michael T.
A1 - Pedersen, Inge Sokilde
A1 - Peixoto, Ana
A1 - Peterlongo, Paolo
A1 - Pharaoh, Paul D. P.
A1 - Plaseska-Karanfilska, Dijana
A1 - Poppe, Bruce
A1 - Presneau, Nadege
A1 - Radice, Paolo
A1 - Rantala, Johanna
A1 - Rennert, Gad
A1 - Risch, Harvey A.
A1 - Saloustros, Emmanouil
A1 - Sanden, Kristin
A1 - Sawyer, Elinor J.
A1 - Schmidt, Marjanka K.
A1 - Schmutzler, Rita K.
A1 - Sharma, Priyanka
A1 - Shu, Xiao-Ou
A1 - Simard, Jaques
A1 - Singer, Christian F.
A1 - Soucy, Penny
A1 - Southey, Melissa C.
A1 - Spinelli, John J.
A1 - Spurdle, Amanda B.
A1 - Stone, Jennifer
A1 - Swerdlow, Anthony J.
A1 - Tapper, William J.
A1 - Taylor, Jack A.
A1 - Teixeira, Manuel R.
A1 - Terry, Mary Beth
A1 - Teulé, Alex
A1 - Thomassen, Mads
A1 - Thöne, Kathrin
A1 - Thull, Darcy L.
A1 - Tischkowitz, Marc
A1 - Toland, Amanda E.
A1 - Torres, Diana
A1 - Truong, Thérèse
A1 - Tung, Nadine
A1 - Vachon, Celine M.
A1 - van Asperen, Christi J.
A1 - van den Ouweland, Ans M. W.
A1 - van Rensburg, Elizabeth J.
A1 - Vega, Ana
A1 - Viel, Alexandra
A1 - Wang, Qin
A1 - Wappenschmidt, Barbara
A1 - Weitzel, Jeffrey N.
A1 - Wendt, Camilla
A1 - Winqvist, Robert
A1 - Yang, Xiaohong R.
A1 - Yannoukakos, Drakoulis
A1 - Ziogas, Argyrios
A1 - Kraft, Peter
A1 - Antoniou, Antonis C.
A1 - Zheng, Wei
A1 - Easton, Douglas F.
A1 - Milne, Roger L.
A1 - Beesley, Jonathan
A1 - Chenevix-Trench, Georgia
T1 - Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer
JF - Nature Communications
N2 - Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
KW - cancer
KW - genetics
Y1 - 2019
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228024
VL - 10
ER -
TY - JOUR
A1 - Dörk, Thilo
A1 - Peterlongo, Peter
A1 - Mannermaa, Arto
A1 - Bolla, Manjeet K.
A1 - Wang, Qin
A1 - Dennis, Joe
A1 - Ahearn, Thomas
A1 - Andrulis, Irene L.
A1 - Anton-Culver, Hoda
A1 - Arndt, Volker
A1 - Aronson, Kristan J.
A1 - Augustinsson, Annelie
A1 - Beane Freeman, Laura E.
A1 - Beckmann, Matthias W.
A1 - Beeghly-Fadiel, Alicia
A1 - Behrens, Sabine
A1 - Bermisheva, Marina
A1 - Blomqvist, Carl
A1 - Bogdanova, Natalia V.
A1 - Bojesen, Stig E.
A1 - Brauch, Hiltrud
A1 - Brenner, Hermann
A1 - Burwinkel, Barbara
A1 - Canzian, Federico
A1 - Chan, Tsun L.
A1 - Chang-Claude, Jenny
A1 - Chanock, Stephen J.
A1 - Choi, Ji-Yeob
A1 - Christiansen, Hans
A1 - Clarke, Christine L.
A1 - Couch, Fergus J.
A1 - Czene, Kamila
A1 - Daly, Mary B.
A1 - dos-Santos-Silva, Isabel
A1 - Dwek, Miriam
A1 - Eccles, Diana M.
A1 - Ekici, Arif B.
A1 - Eriksson, Mikael
A1 - Evans, D. Gareth
A1 - Fasching, Peter A.
A1 - Figueroa, Jonine
A1 - Flyger, Henrik
A1 - Fritschi, Lin
A1 - Gabrielson, Marike
A1 - Gago-Dominguez, Manuela
A1 - Gao, Chi
A1 - Gapstur, Susan M.
A1 - García-Closas, Montserrat
A1 - García-Sáenz, José A.
A1 - Gaudet, Mia M.
A1 - Giles, Graham G.
A1 - Goldberg, Mark S.
A1 - Goldgar, David E.
A1 - Guenél, Pascal
A1 - Haeberle, Lothar
A1 - Haimann, Christopher A.
A1 - Håkansson, Niclas
A1 - Hall, Per
A1 - Hamann, Ute
A1 - Hartman, Mikael
A1 - Hauke, Jan
A1 - Hein, Alexander
A1 - Hillemanns, Peter
A1 - Hogervorst, Frans B. L.
A1 - Hooning, Maartje J.
A1 - Hopper, John L.
A1 - Howell, Tony
A1 - Huo, Dezheng
A1 - Ito, Hidemi
A1 - Iwasaki, Motoki
A1 - Jakubowska, Anna
A1 - Janni, Wolfgang
A1 - John, Esther M.
A1 - Jung, Audrey
A1 - Kaaks, Rudolf
A1 - Kang, Daehee
A1 - Kapoor, Pooja Middha
A1 - Khusnutdinova, Elza
A1 - Kim, Sung-Won
A1 - Kitahara, Cari M.
A1 - Koutros, Stella
A1 - Kraft, Peter
A1 - Kristensen, Vessela N.
A1 - Kwong, Ava
A1 - Lambrechts, Diether
A1 - Le Marchand, Loic
A1 - Li, Jingmei
A1 - Lindström, Sara
A1 - Linet, Martha
A1 - Lo, Wing-Yee
A1 - Long, Jirong
A1 - Lophatananon, Artitaya
A1 - Lubiński, Jan
A1 - Manoochehri, Mehdi
A1 - Manoukian, Siranoush
A1 - Margolin, Sara
A1 - Martinez, Elena
A1 - Matsuo, Keitaro
A1 - Mavroudis, Dimitris
A1 - Meindl, Alfons
A1 - Menon, Usha
A1 - Milne, Roger L.
A1 - Mohd Taib, Nur Aishah
A1 - Muir, Kenneth
A1 - Mulligan, Anna Marie
A1 - Neuhausen, Susan L.
A1 - Nevanlinna, Heli
A1 - Neven, Patrick
A1 - Newman, William G.
A1 - Offit, Kenneth
A1 - Olopade, Olufunmilayo I.
A1 - Olshan, Andrew F.
A1 - Olson, Janet E.
A1 - Olsson, Håkan
A1 - Park, Sue K.
A1 - Park-Simon, Tjoung-Won
A1 - Peto, Julian
A1 - Plaseska-Karanfilska, Dijana
A1 - Pohl-Rescigno, Esther
A1 - Presneau, Nadege
A1 - Rack, Brigitte
A1 - Radice, Paolo
A1 - Rashid, Muhammad U.
A1 - Rennert, Gad
A1 - Rennert, Hedy S.
A1 - Romero, Atocha
A1 - Ruebner, Matthias
A1 - Saloustros, Emmanouil
A1 - Schmidt, Marjanka K.
A1 - Schmutzler, Rita K.
A1 - Schneider, Michael O.
A1 - Schoemaker, Minouk J.
A1 - Scott, Christopher
A1 - Shen, Chen-Yang
A1 - Shu, Xiao-Ou
A1 - Simard, Jaques
A1 - Slager, Susan
A1 - Smichkoska, Snezhana
A1 - Southey, Melissa C.
A1 - Spinelli, John J.
A1 - Stone, Jennifer
A1 - Surowy, Harald
A1 - Swerdlow, Anthony J.
A1 - Tamimi, Rulla M.
A1 - Tapper, William J.
A1 - Teo, Soo H.
A1 - Terry, Mary Beth
A1 - Toland, Amanda E.
A1 - Tollenaar, Rob A. E. M.
A1 - Torres, Diana
A1 - Torres-Mejía, Gabriela
A1 - Troester, Melissa A.
A1 - Truong, Thérèse
A1 - Tsugane, Shoichiro
A1 - Untch, Michael
A1 - Vachon, Celine M.
A1 - van den Ouweland, Ans M. W.
A1 - van Veen, Elke M.
A1 - Vijai, Joseph
A1 - Wendt, Camilla
A1 - Wolk, Alicja
A1 - Yu, Jyh-Cherng
A1 - Zheng, Wei
A1 - Ziogas, Argyrios
A1 - Ziv, Elad
A1 - Dunnig, Alison
A1 - Pharaoh, Paul D. P.
A1 - Schindler, Detlev
A1 - Devilee, Peter
A1 - Easton, Douglas F.
T1 - Two truncating variants in FANCC and breast cancer risk
JF - Scientific Reports
N2 - Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44–1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
KW - oncology
KW - risk factors
Y1 - 2019
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222838
VL - 9
ER -
TY - JOUR
A1 - Markgraf, J. H.
A1 - Cort, J. R.
A1 - Davis, H. A.
A1 - Lindeman, N. I.
A1 - Myers, C. R.
A1 - Kraft, A.
A1 - Christl, Manfred
T1 - Strained Heterocyclic Systems. 20. Basicities of Bicyclic Quinoxalines
N2 - No abstract available
KW - Organische Chemie
Y1 - 1991
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-58584
ER -
TY - JOUR
A1 - Christl, Manfred
A1 - Kraft, A.
T1 - Tricyclo[3.1.1.0\(^{2,6}\)]hexandion (das Valen des o-Benzochinons), Bicyclo[2.1.1]hexan-2,3-dion und Valene eines Chinoxalins, des Phenazins sowie eines Benzophenazins
N2 - No abstract available
KW - Organische Chemie
Y1 - 1988
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-58459
ER -
TY - JOUR
A1 - Christl, Manfred
A1 - Kraft, A.
T1 - Tricyclo[3.1.1.0\(^{2,6}\)]hexandion (the Valen of o-Benzochinons), Bicyclo[2.1.1]hexan-2,3-dion and Valene of a Chinoxalins, of Phenazins and of a Benzophenazine
N2 - No abstract available
KW - Organische Chemie
Y1 - 1988
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-58462
ER -
TY - JOUR
A1 - Christl, Manfred
A1 - Brunn, E.
A1 - Kraft, A.
A1 - Irngartinger, H.
A1 - Huber-Patz, U.
T1 - Nichtbindende Wechselwirkungen in zwei 7-Spirotetracyclo[4.1.0.0\(^{2,4}\).0\(^{3,5}\)]heptanen
T1 - Nonbonded Interactions in two 7-Spirotetracyclo[4.1.0.0\(^{2,4}\).0\(^{3,5}\)]beptanes
N2 - Die Reaktion von Tetrachlordiazocyclopentadien mit Be.nzvalen (2) ergab das Fulven-Derivat 3. Dagegen führten die Umsetzungen von Diazoßuoren und 5-Diazo-10,1 1-dihydro-SH-dibenzo[ a.d]cyclohepten mit 2 zu den erwarteten Spiro-1-pyrazolinen 4 bzw. 5. Die photolytische Abspaltung von Stickstoff aus 4 und 5 lieferte die Spirotetracycloheptane 6 bzw. 7. Die Röntgenstrukturanalyse von 6 beweist einen engen Kontakt zwischen je eineßl Wasserstoffatom der Tetracycloheptan- und der Fluoren-Einheit. Dieser kurze Abstand (2.15 A) ruft Winkelaufweitungen hervor und wird auch als Grund für starke Entschirmungen der betreffenden Protonen und eine formal über sieben Bindungen reichende 0.6-Hz-Kopplung zwischen ihnen angesehen. 7 ist das erste chiralc Tetracyclohcptan. Ursache dafür ist eine nichtebene Konformation des Siebenrings, der bei Raumtemperatur nicht invertiert. Auf der Basis von NOE-Messungen gelang die Zuordnung der tH-NMR-Signale von 6 und 7.
N2 - The reaction or tctrachlorodiazocyclopentadiene with benzvalene (2) gavc, the fulvene derivative 3. In contrast, treatment of diazoßuorene and 5-diazo-1 0,1 1-dihydro·SH -dibenzo[ a,d]cycloheptene with l:afl'orded the expected spiro-1-pyrazolines 4 and 5, respectively. Photolytic extrusion of nitrogen from 4 and S led to the corresponding spirotetracyclobeptanes 6 and 7. The X-ray structure analysis of 6 revealed a close contact between one hydrogen atom cach of the tetracycloheptane and the ßuorene subunits. This short distance (2.15 A) causes an increase in bond angles and is believed to produce strong deshielding of the respective protons and a 0.6-Hz coupling between them, which is formally a long-range coupling across seven bonds. Compound 7 is the first chirat tetracycloheptane. This is due to a nonplanar confonnation of the seven-membered ring, which does not invert at room temperature. On tbe basis of NOE measurements the 1H-NMR signals of 6 and 7 are assigned.
KW - Organische Chemie
KW - 5H-Dibenzo[a
KW - d]cycloheptene
KW - 10
KW - 11-dihydro- / 1-Pyrazoline
KW - Nonbonded Interactions
KW - Spirotetracyclo[4.1.0.02
KW - 4.03
KW - 5]beptanes
KW - Long-range coupling constants
KW - mtrogen extruston
Y1 - 1989
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-58489
ER -
TY - JOUR
A1 - Reuchlein, H.
A1 - Kraft, A.
A1 - Christl, Manfred
A1 - Peters, K.
A1 - Peters, E.-M.
A1 - Schnering, H. G. von
T1 - Reaktionen von Bicyclo[2.1.1]hexenen mit 1,3,4-Oxadiazin-6-onen und dynamische Effekte einem in neungliedrigen, überbrückten, α,β-ungesättigten Enollacton
N2 - No abstract available
KW - Organische Chemie
KW - 1
KW - 3
KW - 4-0xadiazin-6-ones
KW - Diels-Alder reactions
KW - Enol Iactones
KW - Lactone conformations
KW - Line-shape analysis
Y1 - 1991
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-58577
ER -
TY - JOUR
A1 - Christl, Manfred
A1 - Freund, S.
A1 - Henneberger, H.
A1 - Kraft, A.
A1 - Hauck, J.
A1 - Irngartinger, H.
T1 - Several Polycyclic Valence Isomers of Dimethyl [14]Annulene-1,8-dicarboxylate. Reactivity of a "Nonconjugated" Bis(bicyclo[1.1.0]butane)
N2 - Diels-Alder reaction of dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate (5) with benzvalene (4), norbornene, and norbornadiene afforded the azo compounds 7 and 8. Theseare derivatives of 2,3-diazabicyclo[2.2.2]oct-2-ene as is azo compound 3, which had been obtained previously from 5 and 2 equiv of benzvalene (4). The photochemical extrusion of nitrogen from 3, 7, and 8 has been studied. Whereas 7 and 8 on direct irradiation in benzene gave rise exclusively to the bicyclo[2.2.0]hexane derivatives 9 and 10, respectively, from 3 in addition to the bicyclo[2.2.0]hexane 11, the diolefin 1l was formed. Diolefin 12 has cisdouble bonds in the nine-membered ring and is fixed in a boat conformation in a manner so that the two bicyclobutane systems approach each other very closely. This geometry suggests the unusual ring opening of the intermediate 1,4-cyclohexanediyl diradical from a boat conformation, which arises by inversion of the primarily generated boat conformation. Sensitized photolysis of 3 as weilasthat of ll produced the saturated isomer 13 of 11 and 12. The proximity of the bicyclobutane systems in 1l causes unprecedented reactions leading to cage compounds. When ll was heated at 90 °C, a rearrangement to the pentacyclic product 10 took place. Utilization of tetradeuteriated substrate ll-d4 supported a pathway with two diradical intermediates. Behaving in a convcntional manncr, bicyclobutane 9 and bis(bicyclobutane) 11 took up 1 and 2 equiv of thiophenol most probably in a radical-chain addition to give the thioethers 28 and 19, respectively. In contrast, bis(bicyclobutane) ll was converted by 1 equiv of thiophenol into cagc compound 30 in a process involving both the strained a systems. Heating at 80 °C subjected 30 to a reversible Copc rearrangement, resulting in a 6:1 mixture of 31 and 30. When it was treated with bromine, 11 was transformed to cage compound 38. This addition is believed to proceed via a cationic intermediate. The structure of cage compound 10 was established by a singlc-crystal X-ray analysis of dialcohol 11 prepared from 20 and methyllithium.
KW - Organische Chemie
Y1 - 1988
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-58413
ER -
TY - JOUR
A1 - Heuschmann, Peter U.
A1 - Montellano, Felipe A.
A1 - Ungethüm, Kathrin
A1 - Rücker, Viktoria
A1 - Wiedmann, Silke
A1 - Mackenrodt, Daniel
A1 - Quilitzsch, Anika
A1 - Ludwig, Timo
A1 - Kraft, Peter
A1 - Albert, Judith
A1 - Morbach, Caroline
A1 - Frantz, Stefan
A1 - Störk, Stefan
A1 - Haeusler, Karl Georg
A1 - Kleinschnitz, Christoph
T1 - Prevalence and determinants of systolic and diastolic cardiac dysfunction and heart failure in acute ischemic stroke patients: The SICFAIL study
JF - ESC Heart Failure
N2 - Aims
Ischaemic stroke (IS) might induce alterations of cardiac function. Prospective data on frequency of cardiac dysfunction and heart failure (HF) after IS are lacking. We assessed prevalence and determinants of diastolic dysfunction (DD), systolic dysfunction (SD), and HF in patients with acute IS.
Methods and results
The Stroke‐Induced Cardiac FAILure in mice and men (SICFAIL) study is a prospective, hospital‐based cohort study. Patients with IS underwent a comprehensive assessment of cardiac function in the acute phase (median 4 days after IS) including clinical examination, standardized transthoracic echocardiography by expert sonographers, and determination of blood‐based biomarkers. Information on demographics, lifestyle, risk factors, symptoms suggestive of HF, and medical history was collected by a standardized personal interview. Applying current guidelines, cardiac dysfunction was classified based on echocardiographic criteria into SD (left ventricular ejection fraction < 52% in men or <54% in women) and DD (≥3 signs of DD in patients without SD). Clinically overt HF was classified into HF with reduced, mid‐range, or preserved ejection fraction. Between January 2014 and February 2017, 696 IS patients were enrolled. Of them, patients with sufficient echocardiographic data on SD were included in the analyses {n = 644 patients [median age 71 years (interquartile range 60–78), 61.5% male]}. In these patients, full assessment of DD was feasible in 549 patients without SD (94%). Prevalence of cardiac dysfunction and HF was as follows: SD 9.6% [95% confidence interval (CI) 7.6–12.2%]; DD in patients without SD 23.3% (95% CI 20.0–27.0%); and clinically overt HF 5.4% (95% CI 3.9–7.5%) with subcategories of HF with preserved ejection fraction 4.35%, HF with mid‐range ejection fraction 0.31%, and HF with reduced ejection fraction 0.78%. In multivariable analysis, SD and fulfilment of HF criteria were associated with history of coronary heart disease [SD: odds ratio (OR) 3.87, 95% CI 1.93–7.75, P = 0.0001; HF: OR 2.29, 95% CI 1.04–5.05, P = 0.0406] and high‐sensitive troponin T at baseline (SD: OR 1.78, 95% CI 1.31–2.42, P = 0.0003; HF: OR 1.66, 95% CI 1.17–2.33, P = 0.004); DD was associated with older age (OR 1.08, 95% CI 1.05–1.11, P < 0.0001) and treated hypertension vs. no hypertension (OR 2.84, 95% CI 1.23–6.54, P = 0.0405).
Conclusions
A substantial proportion of the study population exhibited subclinical and clinical cardiac dysfunction. SICFAIL provides reliable data on prevalence and determinants of SD, DD, and clinically overt HF in patients with acute IS according to current guidelines, enabling further clarification of its aetiological and prognostic role.
KW - Stroke
KW - Heart failure
KW - Cardiac dysfunction| Brain natriuretic peptide
KW - Troponin
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225656
VL - 8
IS - 2
ER -
TY - JOUR
A1 - Sitter, Magdalena
A1 - Pecks, Ulrich
A1 - Rüdiger, Mario
A1 - Friedrich, Sabine
A1 - Fill Malfertheiner, Sara
A1 - Hein, Alexander
A1 - Königbauer, Josefine T.
A1 - Becke-Jakob, Karin
A1 - Zöllkau, Janine
A1 - Ramsauer, Babett
A1 - Rathberger, Katharina
A1 - Pontones, Constanza A.
A1 - Kraft, Katrina
A1 - Meybohm, Patrick
A1 - Härtel, Christoph
A1 - Kranke, Peter
T1 - Pregnant and postpartum women requiring intensive care treatment for COVID-19 — first data from the CRONOS-registry
JF - Journal of Clinical Medicine
N2 - (1) Background: Data on coronavirus 2 infection during pregnancy vary. We aimed to describe maternal characteristics and clinical presentation of SARS-CoV-2 positive women requiring intensive care treatment for COVID-19 during pregnancy and postpartum period based on data of a comprehensive German surveillance system in obstetric patients. (2) Methods: Data from COVID-19 Related Obstetric and Neonatal Outcome Study (CRONOS), a prospective multicenter registry for SARS-CoV-2 positive pregnant women, was analyzed with respect to ICU treatment. All women requiring intensive care treatment for COVID-19 were included and compared regarding maternal characteristics, course of disease, as well as maternal and neonatal outcomes. (3) Results: Of 2650 cases in CRONOS, 101 women (4%) had a documented ICU stay. Median maternal age was 33 (IQR, 30–36) years. COVID-19 was diagnosed at a median gestational age of 33 (IQR, 28–35) weeks. As the most invasive form of COVID-19 treatment interventions, patients received either continuous monitoring of vital signs without further treatment requirement (n = 6), insufflation of oxygen (n = 30), non-invasive ventilation (n = 22), invasive ventilation (n = 28), or escalation to extracorporeal membrane oxygenation (n = 15). No significant clinical differences were identified between patients receiving different forms of ventilatory support for COVID-19. Prevalence of preterm delivery was significantly higher in women receiving invasive respiratory treatments. Four women died of COVID-19 and six fetuses were stillborn. (4) Conclusions: Our cohort shows that progression of COVID-19 is rare in pregnant and postpartum women treated in the ICU. Preterm birth rate is high and COVID-19 requiring respiratory support increases the risk of poor maternal and neonatal outcome.
KW - maternal critical care
KW - COVID-19
KW - ARDS
KW - SARS-CoV-2
KW - pregnancy
KW - obstetrics
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-255257
SN - 2077-0383
VL - 11
IS - 3
ER -
TY - JOUR
A1 - Jírů-Hillmann, Steffi
A1 - Gabriel, Katharina M. A.
A1 - Schuler, Michael
A1 - Wiedmann, Silke
A1 - Mühler, Johannes
A1 - Dötter, Klaus
A1 - Soda, Hassan
A1 - Rascher, Alexandra
A1 - Benesch, Sonka
A1 - Kraft, Peter
A1 - Pfau, Mathias
A1 - Stenzel, Joachim
A1 - von Nippold, Karin
A1 - Benghebrid, Mohamed
A1 - Schulte, Kerstin
A1 - Meinck, Ralf
A1 - Volkmann, Jens
A1 - Haeusler, Karl Georg
A1 - Heuschmann, Peter U.
T1 - Experiences of family caregivers 3-months after stroke: results of the prospective trans-regional network for stroke intervention with telemedicine registry (TRANSIT-Stroke)
JF - BMC Geriatrics
N2 - Background
Long-term support of stroke patients living at home is often delivered by family caregivers (FC). We identified characteristics of stroke patients being associated with receiving care by a FC 3-months (3 M) after stroke, assessed positive and negative experiences and individual burden of FC caring for stroke patients and determined factors associated with caregiving experiences and burden of FC 3 M after stroke.
Methods
Data were collected within TRANSIT-Stroke, a regional telemedical stroke-network comprising 12 hospitals in Germany. Patients with stroke/TIA providing informed consent were followed up 3 M after the index event. The postal patient-questionnaire was accompanied by an anonymous questionnaire for FC comprising information on positive and negative experiences of FC as well as on burden of caregiving operationalized by the Caregiver Reaction Assessment and a self-rated burden-scale, respectively. Multivariable logistic and linear regression analyses were performed.
Results
Between 01/2016 and 06/2019, 3532 patients provided baseline and 3 M-follow-up- data and 1044 FC responded to questionnaires regarding positive and negative caregiving experiences and caregiving burden. 74.4% of FC were older than 55 years, 70.1% were women and 67.5% were spouses. Older age, diabetes and lower Barthel-Index in patients were significantly associated with a higher probability of receiving care by a FC at 3 M. Positive experiences of FC comprised the importance (81.5%) and the privilege (70.0%) of caring for their relative; negative experiences of FC included financial difficulties associated with caregiving (20.4%). Median overall self-rated burden was 30 (IQR: 0–50; range 0–100). Older age of stroke patients was associated with a lower caregiver burden, whereas younger age of FC led to higher burden. More than half of the stroke patients in whom a FC questionnaire was completed did self-report that they are not being cared by a FC. This stroke patient group tended to be younger, more often male with less severe stroke and less comorbidities who lived more often with a partner.
Conclusions
The majority of caregivers wanted to care for their relatives but experienced burden at the same time. Elderly patients, patients with a lower Barthel Index at discharge and diabetes are at higher risk of needing care by a family caregiver.
Trial registration
The study was registered at “German Clinical Trial Register”: DRKS00011696. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011696
KW - family caregiver
KW - informal care
KW - stroke
KW - stroke care
KW - telemedicine network
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313330
VL - 22
ER -
TY - JOUR
A1 - Gabriel, Katharina M. A.
A1 - Jírů-Hillmann, Steffi
A1 - Kraft, Peter
A1 - Selig, Udo
A1 - Rücker, Victoria
A1 - Mühler, Johannes
A1 - Dötter, Klaus
A1 - Keidel, Matthias
A1 - Soda, Hassan
A1 - Rascher, Alexandra
A1 - Schneider, Rolf
A1 - Pfau, Mathias
A1 - Hoffmann, Roy
A1 - Stenzel, Joachim
A1 - Benghebrid, Mohamed
A1 - Goebel, Tobias
A1 - Doerck, Sebastian
A1 - Kramer, Daniela
A1 - Haeusler, Karl Georg
A1 - Volkmann, Jens
A1 - Heuschmann, Peter U.
A1 - Fluri, Felix
T1 - Two years' experience of implementing a comprehensive telemedical stroke network comprising in mainly rural region: the Transregional Network for Stroke Intervention with Telemedicine (TRANSIT-Stroke)
JF - BMC Neurology
N2 - Background
Telemedicine improves the quality of acute stroke care in rural regions with limited access to specialized stroke care. We report the first 2 years' experience of implementing a comprehensive telemedical stroke network comprising all levels of stroke care in a defined region.
Methods
The TRANSIT-Stroke network covers a mainly rural region in north-western Bavaria (Germany). All hospitals providing acute stroke care in this region participate in TRANSIT-Stroke, including four hospitals with a supra-regional certified stroke unit (SU) care (level III), three of those providing teleconsultation to two hospitals with a regional certified SU (level II) and five hospitals without specialized SU care (level I). For a two-year-period (01/2015 to 12/2016), data of eight of these hospitals were available; 13 evidence-based quality indicators (QIs) related to processes during hospitalisation were evaluated quarterly and compared according to predefined target values between level-I- and level-II/III-hospitals.
Results
Overall, 7881 patients were included (mean age 74.6 years +/- 12.8; 48.4% female). In level-II/III-hospitals adherence of all QIs to predefined targets was high ab initio. In level-I-hospitals, three patterns of QI-development were observed: a) high adherence ab initio (31%), mainly in secondary stroke prevention; b) improvement over time (44%), predominantly related to stroke specific diagnosis and in-hospital organization; c) no clear time trends (25%). Overall, 10 out of 13 QIs reached predefined target values of quality of care at the end of the observation period.
Conclusion
The implementation of the comprehensive TRANSIT-Stroke network resulted in an improvement of quality of care in level-I-hospitals.
KW - pilot project
KW - care tempis
KW - ischemic stroke
KW - thrombolysis
KW - areas
KW - time
KW - hospitals
KW - mortality
KW - outcomes
KW - quality
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229214
VL - 20
ER -
TY - JOUR
A1 - Tappenbeck, Nils
A1 - Schröder, Hannes M.
A1 - Niebergall-Roth, Elke
A1 - Hassinger, Fathema
A1 - Dehio, Ulf
A1 - Dieter, Kathrin
A1 - Kraft, Korinna
A1 - Kerstan, Andreas
A1 - Esterlechner, Jasmina
A1 - Frank, Natasha Y.
A1 - Scharffetter-Kochanek, Karin
A1 - Murphy, George F.
A1 - Orgill, Dennis P.
A1 - Beck, Joachim
A1 - Frank, Markus H.
A1 - Ganss, Christoph
A1 - Kluth, Mark A.
T1 - In vivo safety profile and biodistribution of GMP-manufactured human skin-derived ABCB5-positive mesenchymal stromal cells for use in clinical trials
JF - Cytotherapy
N2 - Background aims
Human dermal ABCB5-expressing mesenchymal stromal cells (ABCB5+ MSCs) represent a promising candidate for stem cell–based therapy of various currently uncurable diseases in several fields of regenerative medicine. We have developed and validated a method to isolate, from human skin samples, and expand ABCB5+ MSCs that meet the guideline criteria of the International Society for Cellular Therapy. We are able to process these cells into a Good Manufacturing Practice–conforming, MSC-based advanced-therapy medicinal product.
Methods
To support the development of ABCB5+ MSCs for potential therapeutic topical, intramuscular and intravenous administration, we have tested our product in a series of Good Laboratory Practice–compliant nonclinical in-vivo studies addressing all relevant aspects of biosafety, including potential long-term persistence and proliferation, distribution to nontarget tissues, differentiation into undesired cell types, ectopic tissue formation, tumor formation and local tissue reaction.
Results
(i) Subcutaneous application of 1 × 107 ABCB5+ MSCs/animal and intravenous application of 2 × 106 ABCB5+ MSCs/animal, respectively, to immunocompromised mice did not result in safety-relevant biodistribution, persistence or proliferation of the cells; (ii) three monthly subcutaneous injections of ABCB5+ MSCs at doses ranging from 1 × 105 to 1 × 107 cells/animal and three biweekly intravenous injections of 2 × 106 ABCB5+ MSCs/animal, respectively, to immunocompromised mice were nontoxic and revealed no tumorigenic potential; and (iii) intramuscular injection of 5 × 106 ABCB5+ MSCs/animal to immunocompromised mice was locally well tolerated.
Discussion
The present preclinical in vivo data demonstrate the local and systemic safety and tolerability of a novel advanced-therapy medicinal product based on human skin-derived ABCB5+ MSCs.
KW - stromal cells
KW - stem cells
KW - MSC
KW - biodistribution
KW - safety
KW - ABCB5
KW - GMP
KW - tumorigenicity
KW - toxicity
KW - persistence
Y1 - 2019
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-240456
VL - 21
ER -