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El-Helou, Sabine M. ; Biegner, Anika-Kerstin ; Bode, Sebastian ; Ehl, Stephan ; Heeg, Maximilian ; Maccari, Maria E. ; Ritterbusch, Henrike ; Speckmann, Carsten ; Rusch, Stephan ; Scheible, Raphael ; Warnatz, Klaus ; Atschekzei, Faranaz ; Beider, Renata ; Ernst, Diana ; Gerschmann, Stev ; Jablonka, Alexandra ; Mielke, Gudrun ; Schmidt, Reinhold E. ; Schürmann, Gesine ; Sogkas, Georgios ; Baumann, Ulrich ; Klemann, Christian ; Viemann, Dorothee ; Bernuth, Horst von ; Krüger, Renate ; Hanitsch, Leif Gunnar ; Scheibenbogen, Carmen ; Wittke, Kirsten ; Albert, Michael H. ; Eichinger, Anna ; Hauck, Fabian ; Klein, Christoph ; Rack-Hoch, Anita ; Sollinger, Franz ; Avila, Anne ; Borte, Michael ; Borte, Stephan ; Fasshauer, Maria ; Hauenherm, Anja ; Kellner, Nils ; Müller, Anna H. ; Ülzen, Anett ; Bader, Peter ; Bakhtiar, Shahrzad ; Lee, Jae-Yun ; Heß, Ursula ; Schubert, Ralf ; Wölke, Sandra ; Zielen, Stefan ; Ghosh, Sujal ; Laws, Hans-Jürgen ; Neubert, Jennifer ; Oommen, Prasad Thomas ; Hönig, Manfred ; Schulz, Ansgar ; Steinmann, Sandra ; Schwarz, Klaus ; Dückers, Gregor ; Lamers, Beate ; Langemeyer, Vanessa ; Niehues, Tim ; Shai, Sonu ; Graf, Dagmar ; Müglich, Carmen ; Schmalzing, Marc ; Schwaneck, Eva C. ; Tony, Hans-Peter ; Dirks, Johannes ; Haase, Gabriele ; Liese, Johannes G. ; Morbach, Henner ; Föll, Dirk ; Hellige, Antje ; Wittkowski, Helmut ; Masjosthusmann, Katja ; Mohr, Michael ; Geberzahn, Linda ; Hedrich, Christian Michael ; Müller, Christiane ; Rösen-Wolff, Angela ; Roesler, Joachim ; Zimmermann, Antje ; Behrends, Uta ; Rieber, Nikolaus ; Schauer, Uwe ; Handgretinger, Rupert ; Holzer, Ursula ; Henes, Jörg Christoph ; Kanz, Lothar ; Boesecke, Christoph ; Rockstroh, Jürgen ; Schwarze-Zander, Carolynne ; Wasmuth, Jan-Christian ; Dilloo, Dagmar ; Hülsmann, Brigitte ; Schönberger, Stefan ; Schreiber, Stefan ; Zeuner, Rainald ; Ankermann, Tobias ; Bismarck, Philipp von ; Huppertz, Hans-Iko ; Kaiser-Labusch, Petra ; Greil, Johann ; Jakoby, Donate ; Kulozik, Andreas ; Metzler, Markus ; Naumann-Bartsch, Nora ; Sobik, Bettina ; Graf, Norbert ; Heine, Sabine ; Kobbe, Robin ; Lehmberg, Kai ; Müller, Ingo ; Herrmann, Friedrich ; Horneff, Gerd ; Klein, Ariane ; Peitz, Joachim ; Schmidt, Nadine ; Bielack, Stefan S. ; Groß-Wieltsch, Ute ; Classen, Carl Friedrich ; Klasen, Jessica ; Deutz, Peter ; Kamitz, Dirk ; Lassay, Lisa ; Tenbrock, Klaus ; Wagner, Norbert ; Bernbeck, Benedikt ; Brummel, Bastian ; Lara-Villacanas, Eusebia ; Münstermann, Esther ; Schneider, Dominik T. ; Tietsch, Nadine ; Westkemper, Marco ; Weiß, Michael ; Kramm, Christof M. ; Kühnle, Ingrid ; Kullman, Silke ; Girschick, Hermann ; Specker, Christof ; Vinnemeier-Laubenthal, Elisabeth ; Haenicke, Henriette ; Schulz, Claudia ; Schweigerer, Lothar ; Müller, Thomas G. ; Stiefel, Martina ; Belohradsky, Bernd H. ; Soetedjo, Veronika ; Kindle, Gerhard ; Grimbacher, Bodo
Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs.
Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel.
Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy.
Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.
Acharya, Shreyasi ; Adamová, Dagmar ; Adler, Alexander ; Adolfsson, Jonatan ; Aglieri Rinella, Gianluca ; Agnello, Michelangelo ; Agrawal, Neelima ; Ahammed, Zubayer ; Ahmad, Shakeel ; Ahn, Sang Un ; Ahuja, Ishaan ; Akbar, Zaenal ; Akindinov, Alexander ; Al-Turany, Mohammad ; Alam, Sk Noor ; Aleksandrov, Dmitry ; Alessandro, Bruno ; Alfanda, Haidar Mas’ud ; Alfaro Molina, Jose Ruben ; Ali, Bushra ; Ali, Yasir ; Alici, Andrea ; Alizadehvandchali, Negin ; Alkin, Anton ; Alme, Johan ; Alocco, Giacomo ; Alt, Torsten ; Altsybeev, Igor ; Anaam, Mustafa Naji ; Andrei, Cristian ; Andreou, Dimitra ; Andronic, Anton ; Anguelov, Venelin ; Antinori, Federico ; Antonioli, Pietro ; Chandra, Anuj ; Apadula, Nicole ; Aphecetche, Laurent Bernard ; Appelshäuser, Harald ; Arcelli, Silvia ; Arnaldi, Roberta ; Arsene, Ionut Cristian ; Arslandok, Mesut ; Augustinus, Andre ; Averbeck, Ralf Peter ; Aziz, Sizar ; Azmi, Mohd Danish ; Badalà, Angela ; Baek, Yong Wook ; Bai, Xiaozhi ; Bailhache, Raphaëlle ; Bailung, Yoshini ; Bala, Renu ; Balbino, Alessandro ; Baldisseri, Alberto ; Balis, Bartosz ; Banerjee, Debjani ; Banoo, Zarina ; Barbera, Roberto ; Barioglio, Luca ; Barlou, Maria ; Barnaföldi, Gergely Gábor ; Barnby, Lee Stuart ; Barret, Valerie ; Bartels, Clara ; Barth, Klaus ; Bartsch, Esther ; Baruffaldi, Filippo ; Bastid, Nicole ; Basu, Sumit ; Batigne, Guillaume ; Battistini, Daniel ; Batyunya, Boris ; Bauri, Dibakar ; Bazo Alba, José Luis ; Bearden, Ian Gardner ; Beattie, Caitlin ; Becht, Pascal ; Belikov, Iouri ; Bell Hechavarria, Ailec de la Caridad ; Bellini, Francesca ; Bellwied, Rene ; Belokurova, Svetlana ; Belyaev, Vladimir ; Bencédi, Gyula ; Beolè, Stefania ; Bercuci, Alexandru ; Berdnikov, Yaroslav ; Berdnikova, Anastasia ; Bergmann, Luisa ; Besoiu, Mihaela Gabriela ; Betev, Latchezar ; Bhaduri, Partha Pratim ; Bhasin, Anju ; Bhat, Inayat Rasool ; Bhat, Mohammad Asif ; Bhattacharjee, Buddhadeb ; Bhattacharya, Purba ; Bianchi, Livio ; Bianchi, Nicola ; Bielčík, Jaroslav ; Bielčíková, Jana ; Biernat, Jacek ; Bilandzic, Ante ; Biro, Gabor ; Biswas, Saikat ; Blair, Justin Thomas ; Blau, Dmitry S. ; Blidaru, Mihail-Bogdan ; Blume, Christoph ; Boca, Gianluigi ; Bock, Friederike ; Bogdanov, Alexey A. ; Boi, Stefano ; Bok, Jeongsu ; Boldizsár, László ; Bolozdynya, Alexander I. ; Bombara, Marek ; Bond, Peter Matthew ; Bonomi, Germano ; Borel, Hervé ; Borissov, Alexander ; Bossi, Hannah ; Botta, Elena ; Bratrud, Lars ; Braun-Munzinger, Peter ; Bregant, Marco ; Broz, Michal ; Bruno, Giuseppe Eugenio ; Buckland, Matthew Daniel ; Budnikov, Dmitry ; Büsching, Henner ; Bufalino, Stefania ; Bugnon, Ophélie ; Bühler, Paul ; Buthelezi, Edith Zinhle ; Butt, Jamila Bashir ; Bylinkin, Alexander ; Bysiak, Sebastian Adam ; Cai, Mengke ; Caines, Helen Louise ; Caliva, Alberto ; Calvo Villar, Ernesto ; Mejia Camacho, Juan Manuel ; Soto Camacho, Rabi ; Camerini, Paolo ; Canedo, Fabio de Moraes Canedo ; Carabaș, Mihai ; Carnesecchi, Francesca ; Caron, Robin Albert Andre ; Castillo Castellanos, Javier Ernesto ; Casula, Ester Anna Rita ; Catalano, Fabio ; Ceballos Sanchez, Cesar ; Chakaberia, Irakli ; Chakraborty, Pritam ; Chandra, Sinjini ; Chapeland, Sylvain ; Chartier, Marielle ; Chattopadhyay, Subhasis ; Chattopadhyay, Sukalyan ; García Chávez, Tonatiuh ; Cheng, T. ; Cheshkov, Cvetan Valeriev ; Cheynis, Brigitte ; Chibante Barroso, Vasco Miguel ; Chinellato, David Dobrigkeit ; Cho, Soyeon ; Chochula, Peter ; Christakoglou, Panagiotis ; Christensen, Christian Holm ; Christiansen, Peter L. ; Chujo, Tatsuya ; Cicalò, Corrado ; Cifarelli, Luisa ; Cindolo, Federico ; Ciupek, Michael Rudolf ; Clai, Giulia ; Cleymans, Jean Willy Andre ; Colamaria, Fabio Filippo ; Colburn, Jonathan Samuel ; Colella, Domenico ; Collu, Alberto ; Colocci, Manuel ; Concas, Matteo ; Conesa Balbastre, Gustavo ; Conesa del Valle, Zaida ; Contin, Giacomo ; Contreras Nuno, Jesus Guillermo ; Coquet, Maurice Louis ; Cormier, Thomas Michael ; Cortese, Pietro ; Cosentino, Mauro Rogerio ; Costa, Filippo ; Costanza, Susanna ; Crochet, Philippe ; Cruz Torres, Reynier ; Cuautle Flores, Eleazar ; Cui, Pengyao ; Cunqueiro Mendez, Leticia ; Dainese, Andrea ; Danisch, Meike Charlotte ; Danu, Andrea ; Das, Prottay ; Das, Prottay ; Das, Supriya ; Dash, Sadhana ; De Caro, Annalisa ; De Cataldo, Giacinto ; De Cilladi, Lorenzo ; Cuveland, Jan de ; De Falco, Alessandro ; De Gruttola, Daniele ; De Marco, Nora ; De Martin, Chiara ; De Pasquale, Salvatore ; Deb, Suman ; Degenhardt, Hermann Franz ; Deja, Kamil Rafal ; Del Grande, Raffaele ; Dello Stritto, Luigi ; Deng, W. ; Dhankher, Preeti ; Di Bari, Domenico ; Di Mauro, Antonio ; Arteche Díaz, Raúl ; Dietel, Thomas ; Ding, Yanchun ; Divià, Roberto ; Dixit, Dhruv Utpalkumar ; Djuvsland, Øystein ; Dmitrieva, Uliana ; Do, Jaehyeon ; Dobrin, Alexandru Florin ; Dönigus, Benjamin ; Dubey, Anand Kumar ; Dubla, Andrea ; Dudi, Sandeep ; Dupieux, Pascal ; Durkac, Martin ; Dzalaiova, Natalia ; Eder, Tabea Maria ; Ehlers, Raymond James ; Eikeland, Viljar Nilsen ; Eisenhut, Florian ; Elia, Domenico ; Erazmus, Barbara Ewa ; Ercolessi, Francesca ; Erhardt, Filip ; Erokhin, Andrey ; Ersdal, Magnus Rentsch ; Espagnon, Bruno ; Eulisse, Giulio ; Evans, David ; Evdokimov, Sergey ; Fabbietti, Laura ; Faggin, Mattia ; Faivre, Julien ; Fan, Feng ; Fan, W. ; Fantoni, Alessandra ; Fasel, Markus ; Fecchio, Pietro ; Feliciello, Alessandro ; Feofilov, Grigori A. ; Fernández Téllez, Arturo ; Ferrero, Andrea ; Ferretti, Alessandro ; Feuillard, Victor Jose Gaston ; Figiel, Jan ; Filova, Vendulka ; Finogeev, Dmitry ; Fionda, Fiorella Maria Celeste ; Fiorenza, Gabriele ; Flor, Fernando Antonio ; Flores, Amanda Nicole ; Foertsch, Siegfried Valentin ; Fokin, Sergey ; Fragiacomo, Enrico ; Frajna, E. ; Francisco, Audrey ; Fuchs, Ulrich ; Funicello, Nicola ; Furget, Christophe ; Furs, Artur ; Gaardhøje, Jens Jørgen ; Gagliardi, Martino ; Gago Medina, Alberto Martín ; Gal, Arthur Willem Jean ; Duarte Galvan, Carlos ; Ganoti, Paraskevi ; Garabatos, Chilo ; Alvarado Garcia, Jesús Ricardo ; Garcia-Solis, Edmundo Javier ; Garg, Kunal ; Gargiulo, Corrado ; Garibli, Aydan ; Garner, Katharina ; Gasik, Piotr ; Gauger, Erin Frances ; Gautam, A. ; Ducati, Maria Beatriz de Leone Gay ; Germain, Marie ; Ghosh, Sanjay Kumar ; Giacalone, Marco ; Gianotti, Paola ; Giubellino, Paolo ; Giubilato, Piero ; Glaenzer, Aude Marie Camille ; Glässel, Peter ; Glimos, Ewa ; Goh, Daniel Jia Qin ; Gonzalez, Victor ; González Trueba, Laura Helena ; Gorbunov, Sergey ; Gorgon, Marek Boguslaw ; Görlich, Lidia Maria ; Gotovac, Sven ; Grabski, Varlen ; Graczykowski, Łukasz Kamil ; Greiner, Leo Clifford ; Grelli, Alessandro ; Grigoraș, Costin ; Grigoriev, Vladislav A. ; Grigoryan, Smbat ; Grosa, Fabrizio ; Große-Oetringhaus, Jan Fiete ; Grosso, Raffaele ; Grund, D. ; Guardiano, G.G. ; Guernane, Rachid ; Guilbaud, Maxime Rene Joseph ; Gulbrandsen, Kristjan Herlache ; Gunji, Taku ; Guo, W. ; Gupta, Anik ; Gupta, Ramni ; Guzman, S.P. ; Gyulai, L. ; Habib, Michael Karim ; Hadjidakis, Cynthia Marie ; Hamagaki, Hideki ; Hamid, Mohammed ; Hannigan, Ryan ; Haque, Md Rihan ; Harlenderova, Alena ; Harris, John W. ; Harton, Austin Vincent ; Hasenbichler, Jan Anton ; Hassan, Hadi ; Hatzifotiadou, Despina ; Hauer, Philip ; Havener, Laura Brittany ; Heckel, Stefan Thomas ; Hellbär, Ernst ; Helstrup, Håvard ; Herman, Tomáš ; Herrera Corral, Gerardo Antonio ; Herrmann, Florian ; Hetland, Kristin Fanebust ; Hillemanns, Hartmut ; Hills, Christopher ; Hippolyte, Boris ; Hofman, B. ; Hohlweger, Bernhard ; Honermann, Jan ; Hong, Geun Hee ; Horak, David ; Hornung, Sebastian ; Horzyk, Adrian ; Hosokawa, Ritsuya ; Hou, Y. ; Hristov, Peter ; Hughes, Charles ; Huhn, Patrick ; Huhta, Laura Maria ; Hulse, Charlotte van ; Humanic, Thomas J. ; Hushnud, Hushnud ; Husova, Lucia Anna ; Hutson, Alek ; Iddon, James Philip ; Ilkaev, Radiy ; Ilyas, Hira ; Inaba, Motoi ; Innocenti, Gian Michele ; Ippolitov, Mikhail ; Isakov, Artem ; Isidori, Tommaso ; Islam, Md Samsul ; Ivanov, Marian ; Ivanov, Vladimir ; Izucheev, Vladimir ; Jablonski, M. ; Jacak, Barbara ; Jacazio, Nicolò ; Jacobs, Peter Martin ; Jadlovska, Slavka ; Jadlovsky, Jan ; Jaelani, Syaefudin ; Jahnke, Cristiane ; Jakubowska, Monika Joanna ; Jalotra, A. ; Janik, Malgorzata Anna ; Janson, Thomas ; Jercic, Marko ; Jevons, Oliver ; Jimenez, A.A.P. ; Jonas, Florian ; Jones, Peter Graham ; Jowett, John M. ; Jung, Jerome ; Jung, Michael ; Junique, Antoine Jean-Simon ; Jusko, Anton ; Kabus, Maja Jadwiga ; Kaewjai, J. ; Kalinak, Peter ; Kalteyer, Annalena Sophie ; Kalweit, Alexander Philipp ; Kaplin, Vladimir ; Karasu Uysal, Ayben ; Karatović, David ; Karavichev, Oleg V. ; Karavicheva, Tatiana L. ; Karczmarczyk, Przemyslaw ; Karpechev, Evgeny ; Kashyap, V. ; Kazantsev, Andrey ; Kebschull, Udo ; Keidel, Ralf ; Keijdener, Darius Laurens D. ; Keil, Markus ; Ketzer, Bernhard ; Khan, Ahsan Mehmood ; Khan, Shaista ; Khanzadeev, Alexei ; Kharlov, Yury ; Khatun, Anisa ; Khuntia, Arvind ; Kileng, Bjarte ; Kim, B. ; Kim, C. ; Kim, Dong Jo ; Kim, Eun Joo ; Kim, J. ; Kim, Jin Sook ; Kim, J. ; Kim, J. ; Kim, M. ; Kim, Se Yong ; 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Mikhaylov, Konstantin ; Mishra, Aditya Nath ; Miśkowiec, Dariusz Czesław ; Modak, Abhi ; Mohanty, Auro Prasad ; Mohanty, Bedangadas ; Mohisin Khan, Mohammed ; Molander, Mikael Andreas ; Moravcova, Zuzana ; Mordasini, Cindy ; Godoy, Denise Aparecida Moreira de ; Morozov, Igor ; Morsch, Andreas ; Mrnjavac, Teo ; Muccifora, Valeria ; Mudnic, Eugen ; Mühlheim, Daniel ; Muhuri, Sanjib ; Mulligan, James Declan ; Mulliri, Alice ; Munhoz, Marcelo Gameiro ; Munzer, Robert Helmut ; Murakami, Hikari ; Murray, Sean ; Musa, Luciano ; Musinsky, Jan ; Myrcha, Julian Wojciech ; Naik, Bharati ; Nair, Rahul Ramachandran ; Nandi, Basanta Kumar ; Nania, Rosario ; Nappi, Eugenio ; Nassirpour, Adrian Fereydon ; Nath, Abhishek ; Nattrass, Christine ; Nayak, Tapan Kumar ; Nayak, Ranjit ; Neagu, Alexandra ; Negru, Adrian-Eduard ; Nellen, Lukas ; Nesbo, Simon Voigt ; Nešković, Gvozden ; Nesterov, Dmitrii ; Nielsen, Borge Svane ; Nielsen, Emil Gorm ; Nikolaev, Sergey ; Nikulin, Sergey ; Nikulin, Vladimir ; Noferini, Francesco ; Noh, S. ; Nomokonov, Petr V. ; Norman, Jaime ; Novitzky, Norbert ; Nowakowski, Piotr ; Nyanin, Alexander ; Nystrand, Joakim Ingemar ; Ogino, Masanori ; Ohlson, Alice ; Okorokov, Vitaly A. ; Oleniacz, Janusz ; Silva, Antonio Carlos Oliveira da ; Oliver, Michael Henry ; Önnerstad, Anna ; Oppedisano, Chiara ; Ortiz Velasquez, Antonio ; Osako, Takumi ; Oskarsson, Anders Nils Erik ; Otwinowski, Jacek Tomasz ; Oya, Motomi ; Oyama, Ken ; Pachmayer, Yvonne C. ; Padhan, Sonali ; Pagano, Davide ; Paić, Guy ; Palasciano, Antonio ; Panebianco, Stefano Matthias ; Park, Jonghan ; Parkkila, Jasper Elias ; Pathak, Surya Prakash ; Patra, Rajendra Nath ; Paul, Biswarup ; Pei, Hua ; Peitzmann, Thomas ; Peng, Xinye ; Pereira, Luis Gustavo ; Pereira da Costa, Hugo Denis Antonio ; Peresunko, Dmitry Yurevich ; Mesa Perez, Guillermo ; Perrin, Sébastien ; Pestov, Yury N. ; Petráček, Vojtech ; Petrov, Viacheslav ; Petrovici, Mihai A. ; Pezzi, Rafael Peretti ; Piano, Stefano ; Pikna, Miroslav ; Pillot, Philippe ; Pinazza, Ombretta ; Pinsky, Lawrence ; Pinto, Chiara ; Pisano, Silvia ; Płoskoń, Mateusz ; Planinic, Mirko ; Pliquett, Fabian ; Poghosyan, Martin G. ; Polichtchouk, Boris ; Politano, S. ; Poljak, Nikola ; Pop, Amalia ; Porteboeuf-Houssais, Sarah Julie ; Porter, Jeffrey Brent ; Pozdniakov, Valeriy ; Prasad, Sidharth Kumar ; Preghenella, Roberto ; Prino, Francesco ; Pruneau, Claude A. ; Pshenichnov, Igor A. ; Puccio, Maximiliano ; Qiu, Shi ; Quaglia, Luca ; Quishpe, Raquel Estefania ; Ragoni, Simone ; Rakotozafindrabe, Andry Malala ; Ramello, Luciano ; Rami, Fouad ; Rodríguez Ramírez, Saúl Aníbal ; Rancien, Thibaut Albert ; Raniwala, Rashmi ; Raniwala, Sudhir ; Räsänen, Sami Sakari ; Rath, Rutuparna ; Ravasenga, Ivan ; Read, Kenneth Francis ; Redelbach, Andreas Ralph ; Redlich, Krzysztof ; Rehman, Attiq ur ; Reichelt, Patrick ; Reidt, Felix ; Reme-Ness, Haakon André ; Rescakova, Zuzana ; Reygers, Klaus ; Riabov, Andrei ; Riabov, Viktor G. ; Richert, Tuva Ora Herenui ; Richter, Matthias Rudolph ; 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We present the first measurement of event-by-event fluctuations in the kaon sector in Pb – Pb collisions at √sNN = 2.76 TeV with the ALICE detector at the LHC. The robust fluctuation correlator νdyn is used to evaluate the magnitude of fluctuations of the relative yields of neutral and charged kaons, as well as the relative yields of charged kaons, as a function of collision centrality and selected kinematic ranges. While the correlator νdyn[K+,K−] exhibits a scaling approximately in inverse proportion of the charged particle multiplicity, νdyn[K0 S ,K±] features a significant deviation from such scaling. Within uncertainties, the value of νdyn[K0 S ,K±] is independent of the selected transverse momentum interval, while it exhibits a pseudorapidity dependence. The results are compared with HIJING, AMPT and EPOS–LHC predictions, and are further discussed in the context of the possible production of disoriented chiral condensates in central Pb – Pb collisions.
Bojunga, Jörg ; Dauth, Nina ; Berner, Christian ; Meyer, Gesine ; Holzer, Katharina ; Voelkl, Lisa ; Herrmann, Eva ; Schroeter, Hartmut ; Zeuzem, Stefan ; Friedrich-Rust, Mireen
Background: Acoustic Radiation Force Impulse (ARFI)-imaging is an ultrasound-based elastography method enabling quantitative measurement of tissue stiffness. The aim of the present study was to evaluate sensitivity and specificity of ARFI-imaging for differentiation of thyroid nodules and to compare it to the well evaluated qualitative real-time elastography (RTE).
Methods: ARFI-imaging involves the mechanical excitation of tissue using acoustic pulses to generate localized displacements resulting in shear-wave propagation which is tracked using correlation-based methods and recorded in m/s. Inclusion criteria were: nodules $5 mm, and cytological/histological assessment. All patients received conventional ultrasound, real-time elastography (RTE) and ARFI-imaging.
Results: One-hundred-fifty-eight nodules in 138 patients were available for analysis. One-hundred-thirty-seven nodules were benign on cytology/histology, and twenty-one nodules were malignant. The median velocity of ARFI-imaging in the healthy thyroid tissue, as well as in benign and malignant thyroid nodules was 1.76 m/s, 1.90 m/s, and 2.69 m/s, respectively. While no significant difference in median velocity was found between healthy thyroid tissue and benign thyroid nodules, a significant difference was found between malignant thyroid nodules on the one hand and healthy thyroid tissue (p = 0.0019) or benign thyroid nodules (p = 0.0039) on the other hand. No significant difference of diagnostic accuracy for the diagnosis of malignant thyroid nodules was found between RTE and ARFI-imaging (0.74 vs. 0.69, p = 0.54). The combination of RTE with ARFI did not improve diagnostic accuracy.
Conclusions: ARFI can be used as an additional tool in the diagnostic work up of thyroid nodules with high negative predictive value and comparable results to RTE.
Friedrich-Rust, Mireen ; Meyer, Gesine ; Dauth, Nina ; Berner, Christian ; Bogdanou, Dimitra ; Herrmann, Eva ; Zeuzem, Stefan ; Bojunga, Jörg
Background: Thyroid Imaging Reporting and Data System (TIRADS) was developed to improve patient management and cost-effectiveness by avoiding unnecessary fine needle aspiration biopsy (FNAB) in patients with thyroid nodules. However, its clinical use is still very limited. Strain elastography (SE) enables the determination of tissue elasticity and has shown promising results for the differentiation of thyroid nodules.
Methods: The aim of the present study was to evaluate the interobserver agreement (IA) of TIRADS developed by Horvath et al. and SE. Three blinded observers independently scored stored images of TIRADS and SE in 114 thyroid nodules (114 patients). Cytology and/or histology was available for all benign (n = 99) and histology for all malignant nodules (n = 15).
Results: The IA between the 3 observers was only fair for TIRADS categories 2–5 (Coheńs kappa = 0.27,p = 0.000001) and TIRADS categories 2/3 versus 4/5 (ck = 0.25,p = 0.0020). The IA was substantial for SE scores 1–4 (ck = 0.66,p<0.000001) and very good for SE scores 1/2 versus 3/4 (ck = 0.81,p<0.000001). 92–100% of patients with TIRADS-2 had benign lesions, while 28–42% with TIRADS-5 had malignant cytology/histology. The negative-predictive-value (NPV) was 92–100% for TIRADS using TIRADS-categories 4&5 and 96–98% for SE using score ES-3&4 for the diagnosis of malignancy, respectively. However, only 11–42% of nodules were in TIRADS-categories 2&3, as compared to 58–60% with ES-1&2.
Conclusions: IA of TIRADS developed by Horvath et al. is only fair. TIRADS and SE have high NPV for excluding malignancy in the diagnostic work-up of thyroid nodules.
Vermehren, Johannes ; Vermehren, Annika ; Mueller, Axel ; Carlebach, Amina ; Lutz, Thomas ; Gute, Peter ; Knecht, Gaby ; Sarrazin, Christoph ; Friedrich-Rust, Mireen ; Forestier, Nicole ; Poynard, Thierry ; Zeuzem, Stefan ; Herrmann, Eva ; Hofmann, Wolf-Peter
Background: Liver fibrosis in human immunodeficiency virus (HIV)-infected individuals is mostly attributable to co-infection with hepatitis B or C. The impact of other risk factors, including prolonged exposure to combined antiretroviral therapy (cART) is poorly understood. Our aim was to determine the prevalence of liver fibrosis and associated risk factors in HIV-infected individuals based on non-invasive fibrosis assessment using transient elastography (TE) and serum biomarkers (Fibrotest [FT]).
Methods: In 202 consecutive HIV-infected individuals (159 men; mean age 47 ± 9 years; 35 with hepatitis-C-virus [HCV] co-infection), TE and FT were performed. Repeat TE examinations were conducted 1 and 2 years after study inclusion.
Results: Significant liver fibrosis was present in 16% and 29% of patients, respectively, when assessed by TE (≥ 7.1 kPa) and FT (> 0.48). A combination of TE and FT predicted significant fibrosis in 8% of all patients (31% in HIV/HCV co-infected and 3% in HIV mono-infected individuals). Chronic ALT, AST and γ-GT elevation was present in 29%, 20% and 51% of all cART-exposed patients and in 19%, 8% and 45.5% of HIV mono-infected individuals. Overall, factors independently associated with significant fibrosis as assessed by TE (OR, 95% CI) were co-infection with HCV (7.29, 1.95-27.34), chronic AST (6.58, 1.30-33.25) and γ-GT (5.17, 1.56-17.08) elevation and time on dideoxynucleoside therapy (1.01, 1.00-1.02). In 68 HIV mono-infected individuals who had repeat TE examinations, TE values did not differ significantly during a median follow-up time of 24 months (median intra-patient changes at last TE examination relative to baseline: -0.2 kPa, p = 0.20).
Conclusions: Chronic elevation of liver enzymes was observed in up to 45.5% of HIV mono-infected patients on cART. However, only a small subset had significant fibrosis as predicted by TE and FT. There was no evidence for fibrosis progression during follow-up TE examinations.
Friedrich-Rust, Mireen ; Rosenberg, William ; Parkes, Julie ; Herrmann, Eva ; Zeuzem, Stefan ; Sarrazin, Christoph
Background: FibroTest (FT) is the most frequently used serum fibrosis marker and consists of an algorithm of five fibrosis markers (alfa2-macroglobulin, apolipoproteinA1, haptoglobin, GGT, bilirubin). The Enhanced Liver Fibrosis (ELF) test consists of an algorithm of three fibrosis markers (hyaluronic acid, amino-terminal propeptide-of-type-III-collagen, tissue-inhibitor of matrix-metaloproteinase-1). While a systematic review has shown comparable results for both individual markers, there has been no direct comparison of both markers. Methods: In the present study, the ELF-test was analyzed retrospectively in patients with chronic liver disease, who received a liver biopsy, transient elastography (TE) and the FibroTest using histology as the reference method. Histology was classified according to METAVIR and the Ludwig's classification (F0-F4) for patients with chronic hepatitis C and B virus (HCV, HBV) infection and primary biliary cirrhosis (PBC), respectively. Results: Seventy-four patients were analysed: 36 with HCV, 10 with HBV, and 28 with PBC. The accuracy (AUROC) for the diagnosis of significant fibrosis (F[greater than or equal to]2) for ELF and FibroTest was 0.78 (95%CI:0.67-0.89) and 0.69 (95%-CI:0.57-0.82), respectively (difference not statistically significant, n.s.). The AUROC for the diagnosis of liver cirrhosis was 0.92 (95%CI:0.83-1,00), and 0.91 (95%CI:0.83-0.99), respectively (n.s.). For 66 patients with reliable TE measurements the AUROC for the diagnosis of significant fibrosis (cirrhosis) for TE, ELF and FT were 0.80 (0.94), 0.76 (0.92), and 0.67 (0.91), respectively (n.s.). Conclusion: FibroTest and ELF can be performed with comparable diagnostic accuracy for the non-invasive staging of liver fibrosis. Serum tests are informative in a higher proportion of patients than transient elastography.
Influence of antibiotic-regimens on intensive-care unit-mortality and liver-cirrhosis as risk factor
(2016)
Friedrich-Rust, Mireen ; Wanger, Beate ; Heupel, Florian ; Filmann, Natalie ; Brodt, Hans-Reinhard ; Kempf, Volkhard A. J. ; Kessel, Johanna ; Wichelhaus, Thomas Alexander ; Herrmann, Eva ; Zeuzem, Stefan ; Bojunga, Jörg
AIM: To assess the rate of infection, appropriateness of antimicrobial-therapy and mortality on intensive care unit (ICU). Special focus was drawn on patients with liver cirrhosis.
METHODS: The study was approved by the local ethical committee. All patients admitted to the Internal Medicine-ICU between April 1, 2007 and December 31, 2009 were included. Data were extracted retrospectively from all patients using patient charts and electronic documentations on infection, microbiological laboratory reports, diagnosis and therapy. Due to the large hepatology department and liver transplantation center, special interest was on the subgroup of patients with liver cirrhosis. The primary statistical-endpoint was the evaluation of the influence of appropriate versus inappropriate antimicrobial-therapy on in-hospital-mortality.
RESULTS: Charts of 1979 patients were available. The overall infection-rate was 53%. Multiresistant-bacteria were present in 23% of patients with infection and were associated with increased mortality (P < 0.000001). Patients with infection had significantly increased in-hospital-mortality (34% vs 17%, P < 0.000001). Only 9% of patients with infection received inappropriate initial antimicrobial-therapy, no influence on mortality was observed. Independent risk-factors for in-hospital-mortality were the presence of septic-shock, prior chemotherapy for malignoma and infection with Pseudomonas spp. Infection and mortality-rate among 175 patients with liver-cirrhosis was significantly higher than in patients without liver-cirrhosis. Infection increased mortality 2.24-fold in patients with cirrhosis. Patients with liver cirrhosis were at an increased risk to receive inappropriate initial antimicrobial therapy.
CONCLUSION: The results of the present study report the successful implementation of early-goal-directed therapy. Liver cirrhosis patients are at increased risk of infection, mortality and to receive inappropriate therapy. Increasing burden are multiresistant-bacteria.
Friedrich-Rust, Mireen ; Schölzel, Fabian ; Maier, Sebastian ; Seeger, Florian Hartmut ; Rey, Julia ; Fichtlscherer, Stephan ; Herrmann, Eva ; Zeuzem, Stefan ; Bojunga, Jörg
Background and aims: Liver steatosis has shown to be associated with coronary artery disease (CAD). The aim of our study was to evaluate the association between the presence and severity of CAD and Non-alcoholic fatty liver disease (NAFLD) assessed by transient elastography (TE) and controlled attenuation parameter (CAP).
Methods: 576 Patients undergoing coronary angiography were enrolled in this prospective study, receiving at least 10 TE and CAP measurements using the FibroScan® M-probe. Clinically relevant CAD (CAD 3) was defined as stenosis with ≥75% reduction of the luminal diameter. NAFLD was determined by CAP ≥234 dB/m. NAFLD with advanced fibrosiswas determined by TE-values ≥7.9kPa in the presence of NAFLD and absence of congestive or right-sided heart failure. Rates and 95% confidence intervals are shown.
Results: 505 patients were available for analysis of NAFLD. However, only 392 patients were available for analysis of NAFLD with advanced fibrosis, since 24 patients had to be excluded due to non valid TE-measurements and 89 patients due to congestive or right-sided heart failure or suspected concomitant liver disease, respectively. 70.5% (66.3%-74.4%) of patients had CAD 3, 71.5% (67.3%-75.4%) were diagnosed with NAFLD, and 11.2% (8.3%-14.8%) with NAFLD with advanced fibrosis. Patients with CAD 3 had higher median CAP-values (273±61 vs. 260±66 dB/m; p = 0.038) and higher degrees of steatosis as compared to patients without CAD 3. While NAFLD was significantly more often diagnosed in patients with CAD 3 (75.0% vs. 63.1%, p = 0.0068), no significant difference was found for NAFLD with advanced fibrosis (10.7% vs. 12.5%, p = 0.60).
Conclusions: Clinically relevant CAD is frequently associated with the presence of NAFLD, but not NAFLD with advanced fibrosis.
Kyriakidou, Georgia ; Friedrich-Rust, Mireen ; Bon, Dimitra ; Sircar, Ishani ; Schrecker, Christopher ; Bogdanou, Dimitra ; Herrmann, Eva ; Bojunga, Jörg
Purpose: The aim of the study was to compare three different elastography methods, namely Strain Elastography (SE), Point Shear-Wave Elastography (pSWE) using Acoustic Radiation Force Impulse (ARFI)-Imaging and 2D-Shear Wave Elastography (2D-SWE), in the same study population for the differentiation of thyroid nodules.
Materials and methods: All patients received a conventional ultrasound scan, SE and 2D-SWE, and all patients except for two received ARFI-Imaging. Cytology/histology of thyroid nodules was used as a reference method. SE measures the relative stiffness within the region of interest (ROI) using the surrounding tissue as reference tissue. ARFI mechanically excites the tissue at the ROI using acoustic pulses to generate localized tissue displacements. 2D-SWE measures tissue elasticity using the velocity of many shear waves as they propagate through the tissue.
Results: 84 nodules (73 benign and 11 malignant) in 62 patients were analyzed. Sensitivity, specificity and NPV of SE were 73%, 70% and 94%, respectively. Sensitivity, specificity and NPV of ARFI and 2D-SWE were 90%, 79%, 98% and 73%, 67%, 94% respectively, using a cut-off value of 1.98m/s for ARFI and 2.65m/s (21.07kPa) for 2D-SWE. The AUROC (Area under the Receiver Operating Characteristic) of SE, ARFI and 2D-SWE for the diagnosis of malignant thyroid nodules were 52%, 86% and 71%, respectively. A significant difference in AUROC was found between SE and ARFI (p = 0.008), while no significant difference was found between ARFI and SWE (86% vs. 71%, p = 0.31), or SWE and SE (71% vs. 52%, p = 0.26).
Conclusion: pSWE using ARFI and 2D-SWE showed comparable results for the differentiation of thyroid nodules. ARFI was superior to elastography using SE.
Dreßler, Melanie ; Friedrich, Theresa ; Lasowski, Natali ; Herrmann, Eva ; Zielen, Stefan ; Schulze, Johannes B.
Background: Physical activity is an important part of life, and hence exercise-induced bronchoconstriction (EIB) can reduce the quality of life. A standardized test is needed to diagnose EIB. The American Thoracic Society (ATS) guidelines recommend an exercise challenge in combination with dry air. We investigated the feasibility of a new, ATS guidelines conform exercise challenge in a cold chamber (ECC) to detect EIB. The aim of this study was to investigate the surrogate marker reaction to methacholine, ECC and exercise challenge in ambient temperature for the prediction of a positive reaction and to re-evaluate the reproducibility of the response to an ECC.
Methods: Seventy-eight subjects aged 6 to 40 years with suspected EIB were recruited for the study. The subjects performed one methacholine challenge, two ECCs, and one exercise challenge at an ambient temperature. To define the sensitivity and specificity of the predictor, a receiver-operating characteristic curve was plotted. The repeatability was evaluated using the method described by Bland and Altman (95% Limits of agreement).
Results: The following cut-off values showed the best combination of sensitivity and specificity: the provocation dose causing a 20% decrease in the forced expiratory volume in 1 s (PD20FEV1) of methacholine: 1.36 mg (AUC 0.69, p < 0.05), the maximal decrease in FEV1 during the ECC: 8.5% (AUC 0.78, p < 0.001) and exercise challenges at ambient temperatures: FEV1 5.2% (AUC 0.64, p = 0.13). The median decline in FEV1 was 14.5% (0.0–64.2) during the first ECC and 10.7% (0.0–52.5) during the second ECC. In the comparison of both ECCs, the Spearman rank correlation of the FEV1 decrease was r = 0.58 (p < 0.001). The 95% limits of agreement (95% LOAs) for the FEV1 decrease were − 17.7 to 26.4%.
Conclusions: The surrogate markers PD20FEV1 of methacholine and maximal decrease in FEV1 during ECC can predict a positive reaction in another ECC, whereas the maximal FEV1 decrease in an exercise challenge at an ambient temperature was not predictive. Compared with previous studies, we can achieve a similar reproducibility with an ECC.
Clinical trial registration: NCT02026492 (retrospectively registered 03/Jan/2014).