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Reitter, Anke ; Stücker, Anja-Undine ; Buxmann, Horst ; Herrmann, Eva ; Haberl, Annette Elisabeth ; Schlößer, Rolf Lambert ; Louwen, Frank
Objective: To assess the prevalence of prenatal screening and of adverse outcome in high-risk pregnancies due to maternal HIV infection.
Study design: The prevalence of prenatal screening in 330 pregnancies of HIV-positive women attending the department for prenatal screening and/or during labour between January 1, 2002 and December 31, 2012, was recorded. Screening results were compared with the postnatal outcome and maternal morbidity, and mother-to-child transmission (MTCT) was evaluated.
Results: One hundred of 330 women (30.5%) had an early anomaly scan, 252 (74.5%) had a detailed scan at 20–22 weeks, 18 (5.5%) had a detailed scan prior to birth, and three (0.9%) had an amniocentesis. In seven cases (2.12%), a fetal anomaly was detected prenatally and confirmed postnatally, while in eight (2.42%) an anomaly was only detected postnatally, even though a prenatal scan was performed. There were no anomalies in the unscreened group. MTCT occurred in three cases (0.9%) and seven fetal and neonatal deaths (2.1%) were reported.
Conclusion: The overall prevalence of prenatal ultrasound screening in our cohort is 74.5%, but often the opportunity for prenatal ultrasonography in the first trimester is missed. In general, the aim should be to offer prenatal ultrasonography in the first trimester in all pregnancies. This allows early reassurance or if fetal disease is suspected, further steps can be taken.
Dultz, Georg ; Seelhof, Martin ; Herrmann, Eva ; Welker, Martin-Walter ; Friedrich-Rust, Mireen ; Teuber, Gerlinde ; Kronenberger, Bernd ; Wagner, Michael von ; Vermehren, Johannes ; Sarrazin, Christoph ; Zeuzem, Stefan ; Hofmann, Wolf-Peter
Background and Aims: In patients with advanced liver cirrhosis due to chronic hepatitis C virus (HCV) infection antiviral therapy with peginterferon and ribavirin is feasible in selected cases only due to potentially life-threatening side effects. However, predictive factors associated with hepatic decompensation during antiviral therapy are poorly defined.
Methods: In a retrospective cohort study, 68 patients with HCV-associated liver cirrhosis (mean MELD score 9.18±2.72) were treated with peginterferon and ribavirin. Clinical events indicating hepatic decompensation (onset of ascites, hepatic encephalopathy, upper gastrointestinal bleeding, hospitalization) as well as laboratory data were recorded at baseline and during a follow up period of 72 weeks after initiation of antiviral therapy. To monitor long term sequelae of end stage liver disease an extended follow up for HCC development, transplantation and death was applied (240weeks, ±SD 136weeks).
Results: Eighteen patients (26.5%) achieved a sustained virologic response. During the observational period a hepatic decompensation was observed in 36.8%. Patients with hepatic decompensation had higher MELD scores (10.84 vs. 8.23, p<0.001) and higher mean bilirubin levels (26.74 vs. 14.63 µmol/l, p<0.001), as well as lower serum albumin levels (38.2 vs. 41.1 g/l, p = 0.015), mean platelets (102.64 vs. 138.95/nl, p = 0.014) and mean leukocytes (4.02 vs. 5.68/nl, p = 0.002) at baseline as compared to those without decompensation. In the multivariate analysis the MELD score remained independently associated with hepatic decompensation (OR 1.56, 1.18–2.07; p = 0.002). When the patients were grouped according to their baseline MELD scores, hepatic decompensation occurred in 22%, 59%, and 83% of patients with MELD scores of 6–9, 10–13, and >14, respectively. Baseline MELD score was significantly associated with the risk for transplantation/death (p<0.001).
Conclusions: Our data suggest that the baseline MELD score predicts the risk of hepatic decompensation during antiviral therapy and thus contributes to decision making when antiviral therapy is discussed in HCV patients with advanced liver cirrhosis.
Long-range angular correlations on the near and away side in p–Pb collisions at √sNN=5.02 TeV
(2013)
Abelev, Betty ; Adam, Jaroslav ; Adamová, Dagmar ; Marshall Adare, Andrew ; Aggarwal, Madan Mohan ; Aglieri Rinella, Gianluca ; Agnello, Michelangelo ; Gabor Agocs, Andras ; Agostinelli, Andrea ; Ahammed, Zubayer ; Ahmad, Nazeer ; Ahmad, Arshad ; Ahn, Sul-Ah ; Ahn, Sang Un ; Ajaz, Muhammad ; Akindinov, Alexander ; Aleksandrov, Dmitry ; Alessandro, Bruno ; Alici, Andrea ; Alkin, Anton ; Jonathan Almaraz Avina, Erick ; Alme, Johan ; Alt, Torsten ; Altini, Valerio ; Altinpinar, Sedat ; Altsybeev, Igor ; Andrei, Cristian ; Andronic, Anton ; Anguelov, Venelin ; Anielski, Jonas ; Daniel Anson, Christopher ; Antičić, Tome ; Antinori, Federico ; Antonioli, Pietro ; Aphecetche, Laurent Bernard ; Appelshäuser, Harald ; Arbor, Nicolas ; Arcelli, Silvia ; Arend, Andreas ; Armesto, Nestor ; Arnaldi, Roberta ; Robert Aronsson, Tomas ; Arsene, Ionut Cristian ; Arslandok, Mesut ; Asryan, Andzhey ; Augustinus, Andre ; Averbeck, Ralf Peter ; Awes, Terry ; Heikki Aysto, Juha ; Danish Azmi, Mohd ; Jakob Bach, Matthias ; Badalà, Angela ; Baek, Yong Wook ; Bailhache, Raphaëlle ; Bala, Renu ; Baldini Ferroli, Rinaldo ; Baldisseri, Alberto ; Baltasar Dos Santos Pedrosa, Fernando ; Ban, Jaroslav ; Chandra Baral, Rama ; Barbera, Roberto ; Barile, Francesco ; Barnaföldi, Gergely Gábor ; Stuart Barnby, Lee ; Barret, Valerie ; Gustaw Bartke, Jerzy ; Basile, Maurizio ; Bastid, Nicole ; Basu, Sumit ; Bathen, Bastian ; Batigne, Guillaume ; Batyunya, Boris ; Heinrich Baumann, Christoph ; Gardner Bearden, Ian ; Beck, Hans ; Kumar Behera, Nirbhay ; Belikov, Iouri ; Bellini, Francesca ; Bellwied, Rene ; Belmont-Moreno, Ernesto ; Bencédi, Gyula ; Beolè, Stefania ; Berceanu, Ionela ; Bercuci, Alexandru ; Berdnikov, Yaroslav ; Berényi, Dániel ; Annick Erica Bergognon, Anais ; Berzano, Dario ; Betev, Latchezar ; Bhasin, Anju ; Kumar Bhati, Ashok ; Bhom, Jihyun ; Bianchi, Livio ; Bianchi, Nicola ; Bielčík, Jaroslav ; Bielčíková, Jana ; Bilandzic, Ante ; Bjelogrlic, Sandro ; Blanco, Francesco ; Blanco, Fernando ; Blau, Dmitry S. ; Blume, Christoph ; Boccioli, Marco ; Boettger, Stefan ; Bogdanov, Alexey A. ; Bøggild, Hans ; Bogolyubsky, Mikhail ; Boldizsar, Laszlo ; Bombara, Marek ; Book, Julian ; Borel, Herve ; Borissov, Alexander ; Bossú, Francesco ; Botje, Michiel ; Botta, Elena ; Braidot, Ermes ; Braun-Munzinger, Peter ; Bregant, Marco ; Breitner, Timo Gunther ; Alexander Broker, Theo ; Allen Browning, Tyler ; Broz, Michal ; Brun, Rene ; Bruna, Elena ; Eugenio Bruno, Giuseppe ; Budnikov, Dmitry ; Büsching, Henner ; Bufalino, Stefania ; Bunčić, Predrag ; Busch, Oliver ; Buthelezi, Edith Zinhle ; Caballero Orduna, Diego ; Caffarri, Davide ; Cai, Xu ; Caines, Helen Louise ; Calvo Villar, Ernesto ; Camerini, Paolo ; Canoa Roman, Veronica ; Cara Romeo, Giovanni ; Carena, Wisla ; Carena, Francesco ; Carlin Filho, Nelson ; Carminati, Federico ; Ofelia Casanova Diaz, Amaya ; Castillo Castellanos, Javier Ernesto ; Castillo Hernández, Juan Francisco ; Anna Rita Casula, Ester ; Catanescu, Vasile ; Cavicchioli, Costanza ; Ceballos Sanchez, Cesar ; Čepila, Jan ; Cerello, Piergiaio ; Chang, Beomsu ; Chapeland, Sylvain ; Fernand Charvet, Jean-Luc ; Chattopadhyay, Sukalyan ; Chattopadhyay, Subhasis ; Chawla, Isha ; Gerard Cherney, Michael ; Cheshkov, Cvetan ; Cheynis, Brigitte ; Miguel Chibante Barroso, Vasco ; Chinellato, David Dobrigkeit ; Chochula, Peter ; Chojnacki, Marek ; Choudhury, Subikash ; Christakoglou, Panagiotis ; Christensen, Christian Holm ; Christiansen, Peter L. ; Chujo, Tatsuya ; Chung, Suh-Urk ; Cicalò, Corrado ; Cifarelli, Luisa ; Cindolo, Federico ; Willy Andre Cleymans, Jean ; Coccetti, Fabrizio ; Colamaria, Fabio Filippo ; Colella, Domenico ; Collu, Alberto ; Conesa Balbastre, Gustavo ; Conesa del Valle, Zaida ; Elizabeth Connors, Megan ; Contin, Giacomo ; Contreras Nuno, Jesus Guillermo ; Michael Cormier, Thomas ; Corrales Morales, Yasser ; Cortese, Pietro ; Cortes Maldonado, Ismael ; Rogerio Cosentino, Mauro ; Costa, Filippo ; Enrique Cotallo, Manuel ; Crescio, Elisabetta ; Crochet, Philippe ; Cruz Alaniz, Emilia ; Cruz Albino, Rigoberto ; Cuautle, Eleazar ; Cunqueiro Mendez, Leticia ; Dainese, Andrea ; Dalsgaard, Hans Hjersing ; Danu, Andrea ; Das, Indranil ; Das, Debasish ; Das, Supriya ; Das, Kushal ; Kumar Dash, Ajay ; Dash, Sadhana ; De, Sudipan ; de Barros, Gabriel ; De Caro, Annalisa ; De Cataldo, Giacinto ; Cuveland, Jan de ; De Falco, Alessandro ; De Gruttola, Daniele ; Delagrange, Hugues ; Deloff, Andrzej ; De Marco, Nora ; Denes, Ervin ; De Pasquale, Salvatore ; Deppman, Airton ; DʼErasmo, Ginevra ; Stefan de Rooij, Raoul ; Angel Diaz Corchero, Miguel ; Di Bari, Domenico ; Dietel, Thomas ; Di Giglio, Carmelo ; Di Liberto, Sergio ; Di Mauro, Antonio ; Di Nezza, Pasquale ; Divià, Roberto ; Djuvsland, Øystein ; Florin Dobrin, Alexandru ; Antoni Dobrowolski, Tadeusz ; Donigus, Benjamin ; Dordic, Olja ; Driga, Olga ; Kumar Dubey, Anand ; Dubla, Andrea ; Ducroux, Laurent ; Dupieux, Pascal ; Dutta Majumdar, A.K. ; Elia, Domenico ; Philip Emschermann, David ; Engel, Heiko ; 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Nania, Rosario ; Nappi, Eugenio ; Nattrass, Christine ; Kumar Nayak, Tapan ; Nazarenko, Sergey ; Nedosekin, Alexander ; Nicassio, Maria ; Niculescu, Mihai ; Svane Nielsen, Bae ; Niida, Takafumi ; Nikolaev, Sergey ; Nikolic, Vedran ; Nikulin, Sergey ; Nikulin, Vladimir ; Steven Nilsen, Bjorn ; Stormo Nilsson, Mads ; Noferini, Francesco ; Nomokonov, Petr V. ; Nooren, Gerardus ; Novitzky, Norbert ; Nyanin, Alexandre ; Nyatha, Anitha ; Nygaard, Casper ; Nystrand, Joakim Ingemar ; Ochirov, Alexander ; Oskar Oeschler, Helmut ; Oh, Saehanseul ; Kun Oh, Sun ; Oleniacz, Janusz ; Carlos Oliveira Da Silva, Antonio ; Oppedisano, Chiara ; Ortiz Velasquez, Antonio ; Nils Erik Oskarsson, Anders ; Krystian Ostrowski, Piotr ; Tomasz Otwinowski, Jacek ; Oyama, Ken ; Ozawa, Kyoichiro ; Chiara Pachmayer, Yvonne ; Pachr, Milos ; Padilla, Fatima ; Pagano, Paola ; Paic, Guy ; Painke, Florian ; Pajares Vales, Carlos ; Kumar Pal, Susanta ; Singh Palaha, Arvinder ; Palmeri, Armando ; Papikyan, Vardanush ; Pappalardo, Giuseppe Salvatore ; Jin Park, Woo ; Passfeld, Annika ; Pastircak, Blahoslav ; Ivanovich Patalakha, Dmitri ; Paticchio, Vincenzo ; Paul, Biswarup ; Pavlinov, Alexei ; Pawlak, Tomasz Jan ; Peitzmann, Thomas ; Denis Antonio Pereira Da Costa, Hugo ; Pereira De Oliveira Filho, Elienos ; Peresunko, Dmitri ; Eugenio Perez Lara, Carlos ; Perini, Diego ; Perrino, Davide ; Stanislaw Peryt, Wiktor ; Pesci, Alessandro ; Peskov, Vladimir ; Pestov, Yury N. ; Petráček, Vojtech ; Petran, Michal ; Petris, Mariana ; Rumenov Petrov, Plamen ; Petrovici, Mihai A. ; Petta, Catia ; Piano, Stefano ; Pikna, Miroslav ; Pillot, Philippe ; Pinazza, Ombretta ; Pinsky, Lawrence ; Pitz, Nora ; Piyarathna, Danthasinghe ; Planinic, Mirko ; Ploskon, Mateusz Andrzej ; Marian Pluta, Jan ; Pocheptsov, Timur ; Pochybova, Sona ; Luis Manuel Podesta Lerma, Pedro ; Poghosyan, Martin G. ; Polak, Karel ; Polichtchouk, Boris ; Pop, Amalia ; Porteboeuf-Houssais, Sarah Julie ; Pospisil, Vladimir ; Potukuchi, Baba ; Prasad, Sidharth Kumar ; Preghenella, Roberto ; Prino, Francesco ; Andre Pruneau, Claude ; Pshenichnov, Igor A. ; Puddu, Giovanna ; Punin, Valery ; Putis, Marian ; Henning Putschke, Jorn ; Quercigh, Emanuele ; Qvigstad, Henrik ; Rachevski, Alexandre ; Rademakers, Alphonse ; Samuli Raiha, Tomi ; Rak, Jan ; Malala Rakotozafindrabe, Andry ; Ramello, Luciano ; Ramirez Reyes, Abdiel ; Raniwala, Rashmi ; Raniwala, Sudhir ; Sakari Rasanen, Sami ; Theodor Rascanu, Bogdan ; Rathee, Deepika ; Francis Read, Kenneth ; Real, Jean-Sébastien ; Redlich, Krzysztof ; Jan Reed, Rosi ; Ur Rehman, Attiq ; Reichelt, Patrick ; Reicher, Martijn ; Arno Ernst Renfordt, Rainer ; Rita Reolon, Anna ; Reshetin, Andrey ; Vincenz Rettig, Felix ; Revol, Jean-Pierre ; Johannes Reygers, Klaus ; Riccati, Lodovico ; Angelo Ricci, Renato ; Richert, Tuva ; Richter, Matthias ; Riedler, Petra ; Riegler, Werner ; Riggi, Francesco ; Rodrı́guez Cahuantzi, Mario ; Rodriguez Manso, Alis ; Roed, Ketil ; Rohr, David ; Röhrich, Dieter ; Romita, Rosa ; Ronchetti, Federico ; Rosnet, Philippe ; Rossegger, Stefan ; Rossi, Andrea ; Sophie Roy, Christelle ; Kumar Roy, Pradip ; Juan Rubio Montero, Antonio ; Rui, Rinaldo ; Russo, Riccardo ; Ryabinkin, Evgeny ; Rybicki, Andrzej ; Sadovskiy, Sergey ; Šafařík, Karel ; Sahoo, Raghunath ; Kumar Sahu, Pradip ; Saini, Jogender ; Sakaguchi, Hiroaki ; Sakai, Shingo ; Sakata, Dosatsu ; Albert Salgado, Carlos ; Salzwedel, Jai ; Singh Sambyal, Sanjeev ; Samsonov, Vladimir ; Sanchez Castro, Xitzel ; Šándor, Ladislav ; Sandoval, Andres ; Sano, Masato ; Santagati, Gianluca ; Santoro, Romualdo ; Jaako Sarkamo, Juho ; Scapparone, Eugenio ; Scarlassara, Fernando ; Paul Scharenberg, Rolf ; Schiaua, Claudiu Cornel ; Schicker, Rainer ; Joachim Schmidt, Christian ; Rudolf Schmidt, Hans ; Schuchmann, Simone ; Schukraft, Jürgen ; Schuster, Tim ; Roland Schutz, Yves ; Eberhard Schwarz, Kilian ; Schweda, Kai ; Scioli, Gilda ; Scomparin, Enrico ; Aaron Scott, Patrick ; Scott, Rebecca ; Segato, Gianfranco ; Selyuzhenkov, Ilya ; Senyukov, Serhiy ; Seo, Jeewon ; Serci, Sergio ; Serradilla, Eulogio ; Sevcenco, Adrian ; Shabetai, Alexandre ; Shabratova, Galina ; Shahoyan, Ruben ; Sharma, Natasha ; Sharma, Satish ; Sharma, Rohini ; Shigaki, Kenta ; Shtejer, Katherin ; Sibiriak, Yury ; Sicking, Eva ; Siddhanta, Sabyasachi ; Siemiarczuk, Teodor ; Olle Rickard Silvermyr, David ; Silvestre, Catherine ; Simatovic, Goran ; Simonetti, Giuseppe ; Narayana Singaraju, Rama ; Singh, Ranbir ; Singha, Subhash ; Singhal, Vikas ; Sinha, Bikash ; Sinha, Tinku ; Sitar, Branislav ; Sitta, Mario ; Skaali, Toralf Bernhard ; Skjerdal, Kyrre ; Smakal, Radek ; Smirnov, Nikolai ; Snellings, Raimond ; Sogaard, Carsten ; Ariel Soltz, Ron ; Son, Hyungsuk ; Song, Jihye ; Song, Myunggeun ; Soos, Csaba ; Soramel, Francesca ; Sputowska, Iwona ; Spyropoulou-Stassinaki, Martha ; Srivastava, Brijesh Kumar ; Stachel, Johanna ; Stan, Ionel ; Stefanek, Grzegorz ; Steinpreis, Matthew ; Anders Stenlund, Evert ; Francois Steyn, Gideon ; Hendrik Stiller, Johannes ; Stocco, Diego ; Stolpovskiy, Mikhail ; Strmen, Peter ; Suaide, Alexandre Alarcon do Passo ; Subieta Vasquez, Martin Alfonso ; Sugitate, Toru ; Suire, Christophe Pierre ; Sultanov, Rishat ; Šumbera, Michal ; Šuša, Tatjana ; Symons, Timothy ; Toledo, Alejandro Szanto de ; Szarka, Imrich ; Szczepankiewicz, Adam ; Krzysztof Szostak, Artur ; Szymanski, Maciej ; Takahashi, Jun ; Tapia Takaki, Jesus Daniel ; Tarantola Peloni, Attilio ; Tarazona Martinez, Alfonso ; Tauro, Arturo ; Tejeda Muñoz, Guillermo ; Telesca, Adriana ; Terrevoli, Cristina ; Mathias Thader, Jochen ; Thomas, Deepa ; Noel Tieulent, Raphael ; Timmins, Anthony Robert ; Tlusty, David ; Toia, Alberica ; Torii, Hisayuki ; Toscano, Luca ; Trubnikov, Victor ; Truesdale, David Christopher ; Henryk Trzaska, Wladyslaw ; Tsuji, Tomoya ; Tumkin, Alexandr ; Turrisi, Rosario ; Spedstad Tveter, Trine ; Glyndwr Ulery, Jason ; Ullaland, Kjetil ; Ulrich, Jochen ; Uras, Antonio ; Urban, Jozef ; Marie Urciuoli, Guido ; Usai, Gianluca ; Vajzer, Michal ; Vala, Martin ; Valencia Palomo, Lizardo ; Vallero, Sara ; Vyvre, Pierre vande ; Leeuwen, Marco van ; Vannucci, Luigi ; Diozcora Vargas, Aurora ; Varma, Raghava ; Vasileiou, Maria ; Vasiliev, Andrey ; Vechernin, Vladimir ; Veldhoen, Misha ; Venaruzzo, Massimo ; Vercellin, Ermanno ; Vergara, Sergio ; Vernet, Renaud ; Verweij, Marta ; Vicković, Linda ; Viesti, Giuseppe ; Viinikainen, Jussi ; Vilakazi, Zabulon ; Villalobos Baillie, Orlando ; Vinogradov, Yury I. ; Vinogradov, Alexander ; Vinogradov, Leonid ; Virgili, Tiziano ; Viyogi, Yogendra P. ; Vodopianov, Alexander ; Voloshin, Sergei ; Voloshin, Kirill ; Volpe, Giacomo ; Haller, Barthélémy von ; Vorobyev, Ivan ; Vranić, Danilo ; Vrlakova, Janka ; Vulpescu, Bogdan ; Vyushin, Alexey ; Wagner, Boris ; Wagner, Vladimir ; Wan, Renzhuo ; Wang, Yaping ; Wang, Yifei ; Wang, Mengliang ; Wang, Dong ; Watanabe, Kengo ; Weber, Michael ; Wessels, Johannes ; Westerhoff, Uwe ; Wiechula, Jens ; Wikne, Jon ; Rudolf Wilde, Martin ; Andrzej Wilk, Grzegorz ; Wilk, Alexander ; Williams, M. Crispin S. ; Windelband, Bernd ; Xaplanteris Karampatsos, Leonidas ; Yaldo, Chris G. ; Yamaguchi, Yorito ; Yang, Hongyan ; Yang, Shiming ; Yasnopolsky, Stanislav ; Yi, JunGyu ; Yin, Zhongbao ; Yoo, In-Kwon ; Yoon, Jongik ; Yu, Weilin ; Yuan, Xianbao ; Yushmanov, Igor ; Zaccolo, Valentina ; Zach, Cenek ; Zampolli, Chiara ; Zaporozhets, Sergey ; Zarochentsev, Andrey ; Závada, Petr ; Zaviyalov, Nikolai ; Paulina Zbroszczyk, Hanna ; Zelnicek, Pierre ; Ion Zgura, Sorin ; Zhalov, Mikhail ; Zhang, Haitao ; Zhang, Xiaoming ; Zhou, Fengchu ; Zhou, You ; Zhou, Daicui ; Zhu, Hongsheng ; Zhu, Jianhui ; Zhu, Jianlin ; Zhu, Xiangrong ; Zichichi, Antonino ; Zimmermann, Alice ; Zinovjev, Gennady M. ; Denis Zoccarato, Yannick ; Zynovyev, Mykhaylo ; Zyzak, Maksym
Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p–Pb collisions at a nucleon–nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5<pT,assoc<pT,trig<4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and pT bins, and the widths show no significant evolution with event multiplicity or pT. These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge.
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.
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.
Welker, Martin-Walter ; Reichert, David ; Susser, Simone ; Sarrazin, Christoph ; Martinez, Yolanda ; Herrmann, Eva ; Zeuzem, Stefan ; Piiper, Albrecht ; Kronenberger, Bernd
Aim: Cellular CD81 is a well characterized hepatitis C virus (HCV) entry factor, while the relevance of soluble exosomal CD81 in HCV pathogenesis is poorly defined. We performed a case-control study to investigate whether soluble CD81 in the exosomal serum fraction is associated with HCV replication and inflammatory activity.
Patients and Methods: Four cohorts were investigated, patients with chronic hepatitis C (n = 37), patients with chronic HCV infection and persistently normal ALT levels (n = 24), patients with long term sustained virologic response (SVR, n = 7), and healthy volunteers (n = 23). Concentration of soluble CD81 was assessed semi-quantitatively after differential centrifugation ranging from 200 g to 100,000 g in the fifth centrifugation fraction by immunoblotting and densitometry.
Results: Soluble CD81 was increased in patients with chronic hepatitis C compared to healthy subjects (p = 0.03) and cured patients (p = 0.017). Patients with chronic HCV infection and persistently normal ALT levels and patients with long term SVR had similar soluble CD81 levels as healthy controls (p>0.2). Overall, soluble CD81 levels were associated with ALT levels (r = 0.334, p = 0.016) and severe liver fibrosis (p = 0.027).
Conclusion: CD81 is increased in the exosomal serum fraction in patients with chronic hepatitis C and appears to be associated with inflammatory activity and severity of fibrosis.
Objective. To examine the effects of clinical hypnosis versus NLP intervention on the success rate of ECV procedures in comparison to a control group.
Methods. A prospective off-centre randomised trial of a clinical hypnosis intervention against NLP of women with a singleton breech fetus at or after 370/7 (259 days) weeks of gestation and normal amniotic fluid index. All 80 participants heard a 20-minute recorded intervention via head phones. Main outcome assessed was success rate of ECV. The intervention groups were compared with a control group with standard medical care alone (n=122).
Results. A total of 42 women, who received a hypnosis intervention prior to ECV, had a 40.5% (n=17), successful ECV, whereas 38 women, who received NLP, had a 44.7% (n=17) successful ECV (P > 0.05). The control group had similar patient characteristics compared to the intervention groups (P > 0.05). In the control group (n = 122) 27.3% (n = 33) had a statistically significant lower successful ECV procedure than NLP (P = 0.05) and hypnosis and NLP (P = 0.03).
Conclusions. These findings suggest that prior clinical hypnosis and NLP have similar success rates of ECV procedures and are both superior to standard medical care alone.
Interleukin-22 predicts severity and death in advanced liver cirrhosis: a prospective cohort study
(2012)
Kronenberger, Bernd ; Rudloff, Ina ; Bachmann, Malte ; Brunner, Friederike ; Kapper, Lisa ; Filmann, Natalie ; Waidmann, Oliver ; Herrmann, Eva ; Pfeilschifter, Josef ; Zeuzem, Stefan ; Piiper, Albrecht ; Mühl, Heiko
Background: Interleukin-22 (IL-22), recently identified as a crucial parameter of pathology in experimental liver damage, may determine survival in clinical end-stage liver disease. Systematic analysis of serum IL-22 in relation to morbidity and mortality of patients with advanced liver cirrhosis has not been performed so far.
Methods: This is a prospective cohort study including 120 liver cirrhosis patients and 40 healthy donors to analyze systemic levels of IL-22 in relation to survival and hepatic complications.
Results: A total of 71% of patients displayed liver cirrhosis-related complications at study inclusion. A total of 23% of the patients died during a mean follow-up of 196 +/- 165 days. Systemic IL-22 was detectable in 74% of patients but only in 10% of healthy donors (P <0.001). Elevated levels of IL-22 were associated with ascites (P = 0.006), hepatorenal syndrome (P <0.0001), and spontaneous bacterial peritonitis (P = 0.001). Patients with elevated IL-22 (>18 pg/ml, n = 57) showed significantly reduced survival compared to patients with regular ([less than or equal to]18 pg/ml) levels of IL-22 (321 days versus 526 days, P = 0.003). Other factors associated with overall survival were high CRP ([greater than or equal to]2.9 mg/dl, P = 0.005, hazard ratio (HR) 0.314, confidence interval (CI) (0.141 to 0.702)), elevated serum creatinine (P = 0.05, HR 0.453, CI (0.203 to 1.012)), presence of liver-related complications (P = 0.028, HR 0.258 CI (0.077 to 0.862)), model of end stage liver disease (MELD) score [greater than or equal to]20 (P = 0.017, HR 0.364, CI (0.159 to 0.835)) and age (P = 0.011, HR 1.047, CI (1.011 to 1.085)). Adjusted multivariate Cox proportional-hazards analysis identified elevated systemic IL-22 levels as independent predictors of reduced survival (P = 0.007, HR 0.218, CI (0.072 to 0.662)).
Conclusions: In patients with liver cirrhosis, elevated systemic IL-22 levels are predictive for reduced survival independently from age, liver-related complications, CRP, creatinine and the MELD score. Thus, processes that lead to a rise in systemic interleukin-22 may be relevant for prognosis of advanced liver cirrhosis.
Güller, Saskia ; Allwinn, Regina ; Mousset, Sabine ; Martin, Hans ; Wieters, Imke ; Herrmann, Eva ; Serve, Hubert ; Bickel, Markus ; Bug, Gesine
Seroconversion rates following influenza vaccination in patients with hematologic malignancies after hematopoietic stem cell transplantation (HSCT) are known to be lower compared to healthy adults. The aim of our diagnostic study was to determine the rate of seroconversion after 1 or 2 doses of a novel split virion, inactivated, AS03-adjuvanted pandemic H1N1 influenza vaccine (A/California/7/2009) in HSCT recipients (ClinicalTrials.gov Identifier: NCT01017172). Blood samples were taken before and 21 days after a first dose and 21 days after a second dose of the vaccine. Antibody (AB) titers were determined by hemagglutination inhibition assay. Seroconversion was defined by either an AB titer of ≤1:10 before and ≥1:40 after or ≥1:10 before and ≥4-fold increase in AB titer 21 days after vaccination. Seventeen patients (14 allogeneic, 3 autologous HSCT) received 1 dose and 11 of these patients 2 doses of the vaccine. The rate of seroconversion was 41.2% (95% confidence interval [CI] 18.4-67.1) after the first and 81.8% (95% CI 48.2-97.7) after the second dose. Patients who failed to seroconvert after 1 dose of the vaccine were more likely to receive any immunosuppressive agent (P = .003), but time elapsed after or type of HSCT, age, sex, or chronic graft-versus-host disease was not different when compared to patients with seroconversion. In patients with hematologic malignancies after HSCT the rate of seroconversion after a first dose of an adjuvanted H1N1 influenza A vaccine was poor, but increased after a second dose.
Bitzegeio, Julia ; Bankwitz, Dorothea ; Hueging, Kathrin ; Haid, Sibylle ; Brohm, Christiane ; Zeisel, Mirjam B. ; Herrmann, Eva ; Iken, Marcus ; Ott, Michael ; Baumert, Thomas ; Pietschmann, Thomas
Hepatitis C virus (HCV) naturally infects only humans and chimpanzees. The determinants responsible for this narrow species tropism are not well defined. Virus cell entry involves human scavenger receptor class B type I (SR-BI), CD81, claudin-1 and occludin. Among these, at least CD81 and occludin are utilized in a highly species-specific fashion, thus contributing to the narrow host range of HCV. We adapted HCV to mouse CD81 and identified three envelope glycoprotein mutations which together enhance infection of cells with mouse or other rodent receptors approximately 100-fold. These mutations enhanced interaction with human CD81 and increased exposure of the binding site for CD81 on the surface of virus particles. These changes were accompanied by augmented susceptibility of adapted HCV to neutralization by E2-specific antibodies indicative of major conformational changes of virus-resident E1/E2-complexes. Neutralization with CD81, SR-BI- and claudin-1-specific antibodies and knock down of occludin expression by siRNAs indicate that the adapted virus remains dependent on these host factors but apparently utilizes CD81, SR-BI and occludin with increased efficiency. Importantly, adapted E1/E2 complexes mediate HCV cell entry into mouse cells in the absence of human entry factors. These results further our knowledge of HCV receptor interactions and indicate that three glycoprotein mutations are sufficient to overcome the species-specific restriction of HCV cell entry into mouse cells. Moreover, these findings should contribute to the development of an immunocompetent small animal model fully permissive to HCV.
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.
Adiwijaya, Bambang S. ; Herrmann, Eva ; Hare, Brian ; Kieffer, Tara ; Lin, Chao ; Kwong, Ann D. ; Garg, Varun ; Randle, John C. R. ; Sarrazin, Christoph ; Zeuzem, Stefan ; Caron, Paul R.
Variants resistant to compounds specifically targeting HCV are observed in clinical trials. A multi-variant viral dynamic model was developed to quantify the evolution and in vivo fitness of variants in subjects dosed with monotherapy of an HCV protease inhibitor, telaprevir. Variant fitness was estimated using a model in which variants were selected by competition for shared limited replication space. Fitness was represented in the absence of telaprevir by different variant production rate constants and in the presence of telaprevir by additional antiviral blockage by telaprevir. Model parameters, including rate constants for viral production, clearance, and effective telaprevir concentration, were estimated from 1) plasma HCV RNA levels of subjects before, during, and after dosing, 2) post-dosing prevalence of plasma variants from subjects, and 3) sensitivity of variants to telaprevir in the HCV replicon. The model provided a good fit to plasma HCV RNA levels observed both during and after telaprevir dosing, as well as to variant prevalence observed after telaprevir dosing. After an initial sharp decline in HCV RNA levels during dosing with telaprevir, HCV RNA levels increased in some subjects. The model predicted this increase to be caused by pre-existing variants with sufficient fitness to expand once available replication space increased due to rapid clearance of wild-type (WT) virus. The average replicative fitness estimates in the absence of telaprevir ranged from 1% to 68% of WT fitness. Compared to the relative fitness method, the in vivo estimates from the viral dynamic model corresponded more closely to in vitro replicon data, as well as to qualitative behaviors observed in both on-dosing and long-term post-dosing clinical data. The modeling fitness estimates were robust in sensitivity analyses in which the restoration dynamics of replication space and assumptions of HCV mutation rates were varied.
Bacterial porin disrupts mitochondrial membrane potential and sensitizes host cells to apoptosis
(2009)
Kozjak-Pavlovic, Vera ; Dian-Lothrop, Elke A. ; Meinecke, Michael ; Kepp, Oliver ; Ross, Katharina ; Rajalingam, Krishnaraj ; Harsman, Anke ; Hauf, Eva ; Brinkmann, Volker ; Günther, Dirk ; Herrmann, Ines ; Hurwitz, Robert ; Rassow, Joachim ; Wagner, Richard ; Rudel, Thomas
The bacterial PorB porin, an ATP-binding beta-barrel protein of pathogenic Neisseria gonorrhoeae, triggers host cell apoptosis by an unknown mechanism. PorB is targeted to and imported by host cell mitochondria, causing the breakdown of the mitochondrial membrane potential (delta psi m). Here, we show that PorB induces the condensation of the mitochondrial matrix and the loss of cristae structures, sensitizing cells to the induction of apoptosis via signaling pathways activated by BH3-only proteins. PorB is imported into mitochondria through the general translocase TOM but, unexpectedly, is not recognized by the SAM sorting machinery, usually required for the assembly of beta-barrel proteins in the mitochondrial outer membrane. PorB integrates into the mitochondrial inner membrane, leading to the breakdown of delta psi m. The PorB channel is regulated by nucleotides and an isogenic PorB mutant defective in ATP-binding failed to induce delta psi m loss and apoptosis, demonstrating that dissipation of delta psi m is a requirement for cell death caused by neisserial infection.