Author: "Mohr, R" / Publication Year Range: Last 3 years - Searchworks@Jio Institute Digital Library Search Results

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58 results on '"Mohr, R"'

1. Preoperative Immunotherapy in Hepatocellular Carcinoma: Current State of the Art

Author: Laschtowitz A, Roderburg C, Tacke F, and Mohr R
Subjects: hepatocellular carcinoma, immune oncology, checkpoint inhibitor, neoadjuvant, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Alena Laschtowitz,1 Christoph Roderburg,2 Frank Tacke,1 Raphael Mohr1 1Department of Hepatology and Gastroenterology, Charité – Universitätsmedizin Berlin, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Berlin, Germany; 2Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Düsseldorf, GermanyCorrespondence: Raphael Mohr, Department of Hepatology and Gastroenterology, Charité – Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, 13353, Germany, Email raphael.mohr@charite.deAbstract: Hepatocellular carcinoma (HCC) is a malignancy that requires multidisciplinary evaluation to develop individualized and tailored treatment concepts. While liver resection and transplantation represent the mainstay of curative treatment in patients with early-stage HCC, disease recurrence remains an important burden. Immune checkpoint inhibitors (ICI) have become standard of care in the palliative setting, achieving promising response rates with overall good tolerability. Accordingly, ICIs are being evaluated in (neo)adjuvant concepts in order to improve survival. Nevertheless, neoadjuvant therapies are not recommended by current guidelines as they have not been proven to improve the outcome in large Phase III trials yet. Especially in the context of liver transplantation (LT), perioperative ICI usage is in need of a particularly critical risk–benefit assessment, as the immunotherapy may significantly increase the risk of rejection. In this review, we summarize available data on ICI-based perioperative treatment strategies in HCC. We discuss current drawbacks and challenges of this treatment concept and specifically highlight the risk of allograft rejection when ICI are given in patients (subsequently) considered for liver transplantation.Keywords: hepatocellular carcinoma, immune oncology, checkpoint inhibitor, neoadjuvant
Published: 2023

2. Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Author: Ferrari, A, Santomauro, D, Aali, A, Abate, Y, Abbafati, C, Abbastabar, H, Abd ElHafeez, S, Abdelmasseh, M, Abd-Elsalam, S, Abdollahi, A, Abdullahi, A, Abegaz, K, Abeldaño Zuñiga, R, Aboagye, R, Abolhassani, H, Abreu, L, Abualruz, H, Abu-Gharbieh, E, Abu-Rmeileh, N, Ackerman, I, Addo, I, Addolorato, G, Adebiyi, A, Adepoju, A, Adewuyi, H, Afyouni, S, Afzal, S, Agodi, A, Ahmad, A, Ahmad, D, Ahmad, F, Ahmad, S, Ahmed, A, Ahmed, L, Ahmed, M, Ajami, M, Akinosoglou, K, Akkaif, M, Al Hasan, S, Alalalmeh, S, Al-Aly, Z, Albashtawy, M, Aldridge, R, Alemu, M, Alemu, Y, Alene, K, Al-Gheethi, A, Alharrasi, M, Alhassan, R, Ali, M, Ali, R, Ali, S, Alif, S, Aljunid, S, Al-Marwani, S, Almazan, J, Alomari, M, Al-Omari, B, Altaany, Z, Alvis-Guzman, N, Alvis-Zakzuk, N, Alwafi, H, Al-Wardat, M, Al-Worafi, Y, Aly, S, Alzoubi, K, Amare, A, Amegbor, P, Ameyaw, E, Amin, T, Amindarolzarbi, A, Amiri, S, Amugsi, D, Ancuceanu, R, Anderlini, D, Anderson, D, Andrade, P, Andrei, C, Ansari, H, Antony, C, Anwar, S, Anwer, R, Anyanwu, P, Arab, J, Arabloo, J, Arafat, M, Araki, D, Aravkin, A, Arkew, M, Armocida, B, Arndt, M, Arooj, M, Artamonov, A, Aruleba, R, Arumugam, A, Ashbaugh, C, Ashemo, M, Ashraf, M, Asika, M, Askari, E, Astell-Burt, T, Athari, S, Atorkey, P, Atout, M, Atreya, A, Aujayeb, A, Ausloos, M, Avan, A, Awotidebe, A, Awuviry-Newton, K, Ayala Quintanilla, B, Ayuso-Mateos, J, Azadnajafabad, S, Azevedo, R, Babu, A, Badar, M, Badiye, A, Baghdadi, S, Bagheri, N, Bah, S, Bai, R, Baker, J, Bakkannavar, S, Bako, A, Balakrishnan, S, Bam, K, Banik, P, Barchitta, M, Bardhan, M, Bardideh, E, Barker-Collo, S, Barqawi, H, Barrow, A, Barteit, S, Barua, L, Bashiri Aliabadi, S, Basiru, A, Basu, S, Bathini, P, Batra, K, Baune, B, Bayileyegn, N, Behnam, B, Behnoush, A, Beiranvand, M, Bejarano Ramirez, D, Bell, M, Bello, O, Beloukas, A, Bensenor, I, Berezvai, Z, Bernabe, E, Bernstein, R, Bettencourt, P, Bhagavathula, A, Bhala, N, Bhandari, D, Bhargava, A, Bhaskar, S, Bhat, V, Bhatti, G, Bhatti, J, Bhatti, M, Bhatti, R, Bhutta, Z, Bikbov, B, Bishai, J, Bisignano, C, Bitra, V, Bjørge, T, Bodolica, V, Bodunrin, A, Bogale, E, Bonakdar Hashemi, M, Bonny, A, Bora Basara, B, Borhany, H, Boxe, C, Brady, O, Bragazzi, N, Braithwaite, D, Brant, L, Brauer, M, Breitner, S, Brenner, H, Brown, J, Brugha, T, Bulamu, N, Buonsenso, D, Burkart, K, Burns, R, Busse, R, Bustanji, Y, Butt, Z, Byun, J, Caetano dos Santos, F, Calina, D, Cámera, L, Campos-Nonato, I, Cao, C, Capodici, A, Carr, S, Carreras, G, Carugno, A, Carvalho, M, Castaldelli-Maia, J, Castañeda-Orjuela, C, Castelpietra, G, Catapano, A, Cattaruzza, M, Caye, A, Cegolon, L, Cembranel, F, Cenderadewi, M, Cerin, E, Chakraborty, P, Chan, J, Chan, R, Chandika, R, Chandrasekar, E, Charalampous, P, Chattu, V, Chatzimavridou-Grigoriadou, V, Chen, A, Chen, C, Chen, H, Chen, N, Cheng, E, Chimed-Ochir, O, Chimoriya, R, Ching, P, Cho, W, Choi, S, Chong, B, Chong, Y, Choudhari, S, Chowdhury, R, Christensen, S, Chu, D, Chukwu, I, Chung, E, Chutiyami, M, Claassens, M, Cogen, R, Columbus, A, Conde, J, Cortesi, P, Cousin, E, Criqui, M, Cruz-Martins, N, Dadras, O, Dai, S, Dai, X, Dai, Z, Dalaba, M, Damiani, G, Das, J, Das, S, Dashti, M, Dávila-Cervantes, C, Davletov, K, De Leo, D, Debele, A, Debopadhaya, S, Decleene, N, Deeba, F, Degenhardt, L, Del Bo', C, Delgado-Enciso, I, Demetriades, A, Denova-Gutiérrez, E, Dervenis, N, Desai, H, Desai, R, Deuba, K, Dhama, K, Dharmaratne, S, Dhingra, S, Dias da Silva, D, Diaz, D, Diaz, L, Diaz, M, Dima, A, Ding, D, Dirac, M, Do, T, do Prado, C, Dohare, S, Dominguez, R, Dong, W, Dongarwar, D, D'Oria, M, Dorsey, E, Doshmangir, L, Dowou, R, Driscoll, T, Dsouza, H, Dsouza, V, Dube, J, Dumith, S, Duncan, B, Duraes, A, Duraisamy, S, Durojaiye, O, Dzianach, P, Dziedzic, A, Eboreime, E, Ebrahimi, A, Edinur, H, Edvardsson, D, Eikemo, T, Eini, E, Ekholuenetale, M, Ekundayo, T, El Sayed, I, El Tantawi, M, Elbarazi, I, Elemam, N, Elgohary, G, Elhadi, M, Elmeligy, O, Elnahas, G, Elshaer, M, Elsohaby, I, Engelbert Bain, L, Erkhembayar, R, Eshrati, B, Estep, K, Fabin, N, Fagbamigbe, A, Falzone, L, Fareed, M, Farinha, C, Faris, M, Faro, A, Farrokhi, P, Fatehizadeh, A, Fauk, N, Feigin, V, Feng, X, Fereshtehnejad, S, Feroze, A, Ferreira, N, Ferreira, P, Fischer, F, Flavel, J, Flood, D, Flor, L, Foigt, N, Folayan, M, Force, L, Fortuna, D, Foschi, M, Franklin, R, Freitas, A, Fukumoto, T, Furtado, J, Gaal, P, Gadanya, M, Gaidhane, A, Gaihre, S, Galali, Y, Ganbat, M, Gandhi, A, Ganesan, B, Ganie, M, Ganiyani, M, Gardner, W, Gebi, T, Gebregergis, M, Gebrehiwot, M, Gebremariam, T, Gebremeskel, T, Gela, Y, Georgescu, S, Getachew Obsa, A, Gething, P, Getie, M, Ghadiri, K, Ghadirian, F, Ghailan, K, Ghajar, A, Ghasemi, M, Ghasempour Dabaghi, G, Ghasemzadeh, A, Ghazy, R, Gholamrezanezhad, A, Ghorbani, M, Ghotbi, E, Gibson, R, Gill, T, Ginindza, T, Girmay, A, Glasbey, J, Göbölös, L, Godinho, M, Goharinezhad, S, Goldust, M, Golechha, M, Goleij, P, Gona, P, Gorini, G, Goulart, A, Grada, A, Grivna, M, Guan, S, Guarducci, G, Gubari, M, Gudeta, M, Guha, A, Guicciardi, S, Gulati, S, Gulisashvili, D, Gunawardane, D, Guo, C, Gupta, A, Gupta, B, Gupta, I, Gupta, M, Gupta, R, Gupta, V, Gutiérrez, R, Habibzadeh, F, Habibzadeh, P, Haddadi, R, Hadi, N, Haep, N, Hafezi-Nejad, N, Hafiz, A, Hagins, H, Halboub, E, Halimi, A, Haller, S, Halwani, R, Hamilton, E, Hankey, G, Hannan, M, Haque, M, Harapan, H, Haro, J, Hartvigsen, J, Hasaballah, A, Hasan, I, Hasanian, M, Hasnain, M, Hassan, A, Haubold, J, Havmoeller, R, Hay, S, Hayat, K, Hebert, J, Hegazi, O, Heidari, G, Helfer, B, Hemmati, M, Hendrie, D, Henson, C, Hezam, K, Hiraike, Y, Hoan, N, Holla, R, Hon, J, Hossain, M, Hosseinzadeh, H, Hosseinzadeh, M, Hostiuc, M, Hostiuc, S, Hsu, J, Huang, J, Hugo, F, Hushmandi, K, Hussain, J, Hussein, N, Huynh, C, Huynh, H, Hwang, B, Iannucci, V, Ihler, A, Ikiroma, A, Ikuta, K, Ilesanmi, O, Ilic, I, Ilic, M, Imam, M, Immurana, M, Irham, L, Islam, M, Islam, S, Islami, F, Ismail, F, Ismail, N, Isola, G, Iwagami, M, Iwu, C, Iyer, M, Jaafari, J, Jacobsen, K, Jadidi-Niaragh, F, Jafarinia, M, Jaggi, K, Jahankhani, K, Jahanmehr, N, Jahrami, H, Jain, A, Jain, N, Jairoun, A, Jaiswal, A, Jakovljevic, M, Jatau, A, Javadov, S, Javaheri, T, Jayapal, S, Jayaram, S, Jee, S, Jeganathan, J, Jeyakumar, A, Jha, A, Jiang, H, Jin, Y, Jonas, J, Joo, T, Joseph, A, Joseph, N, Joshua, C, Jozwiak, J, Jürisson, M, K, V, Kaambwa, B, Kabir, A, Kabir, Z, Kadashetti, V, Kalani, R, Kalankesh, L, Kaliyadan, F, Kalra, S, Kamenov, K, Kamyari, N, Kanagasabai, T, Kandel, H, Kanmanthareddy, A, Kanmodi, K, Kantar, R, Karaye, I, Karim, A, Karimi, S, Karimi, Y, Kasraei, H, Kassel, M, Kauppila, J, Kawakami, N, Kayode, G, Kazemi, F, Kazemian, S, Keikavoosi-Arani, L, Keller, C, Kempen, J, Kerr, J, Keshtkar, K, Kesse-Guyot, E, Keykhaei, M, Khajuria, H, Khalaji, A, Khalid, A, Khalid, N, Khalilian, A, Khamesipour, F, Khan, A, Khan, I, Khan, M, Khanmohammadi, S, Khatab, K, Khatami, F, Khatatbeh, M, Khater, A, Khayat Kashani, H, Khidri, F, Khodadoust, E, Khormali, M, Khorrami, Z, Kifle, Z, Kim, M, Kimokoti, R, Kisa, A, Kisa, S, Knudsen, A, Kocarnik, J, Kochhar, S, Koh, H, Kolahi, A, Kompani, F, Koren, G, Korzh, O, Kosen, S, Koulmane Laxminarayana, S, Krishan, K, Krishna, V, Krishnamoorthy, V, Kuate Defo, B, Kuddus, M, Kuitunen, I, Kulkarni, V, Kumar, M, Kumar, N, Kumar, R, Kurmi, O, Kusuma, D, Kyu, H, La Vecchia, C, Lacey, B, Ladan, M, Laflamme, L, Lafranconi, A, Lahariya, C, Lai, D, Lal, D, Lalloo, R, Lallukka, T, Lám, J, Lan, Q, Lan, T, Landires, I, Lanfranchi, F, Langguth, B, Laplante-Lévesque, A, Larijani, B, Larsson, A, Lasrado, S, Lauriola, P, Le, H, Le, L, Le, N, Le, T, Leasher, J, Ledda, C, Lee, M, Lee, P, Lee, S, Lee, W, Lee, Y, Legrand, K, Lenzi, J, Leong, E, Leung, J, Li, M, Li, W, Li, X, Li, Y, Lim, L, Lim, S, Lindstrom, M, Linn, S, Liu, G, Liu, R, Liu, S, Liu, W, Liu, X, Llanaj, E, Lo, C, López-Bueno, R, Loreche, A, Lorenzovici, L, Lozano, R, Lubinda, J, Lucchetti, G, Lunevicius, R, Lusk, J, Lv, H, Ma, Z, Machairas, N, Madureira-Carvalho, Á, Magaña Gómez, J, Maghazachi, A, Maharjan, P, Mahasha, P, Maheri, M, Mahjoub, S, Mahmoud, M, Mahmoudi, E, Majeed, A, Makris, K, Malakan Rad, E, Malhotra, K, Malik, A, Malik, I, Malta, D, Manla, Y, Mansour, A, Mansouri, P, Mansournia, M, Mantilla Herrera, A, Mantovani, L, Manu, E, Marateb, H, Mardi, P, Martinez, G, Martinez-Piedra, R, Martini, D, Martins-Melo, F, Martorell, M, Marx, W, Maryam, S, Marzo, R, Mathangasinghe, Y, Mathieson, S, Mathioudakis, A, Mattumpuram, J, Maugeri, A, Mayeli, M, Mazidi, M, Mazzotti, A, Mcgrath, J, Mckee, M, Mckowen, A, Mcphail, M, Mehrabani-Zeinabad, K, Mehrabi Nasab, E, Mekene Meto, T, Mendoza, W, Menezes, R, Mensah, G, Mentis, A, Meo, S, Meresa, H, Meretoja, A, Meretoja, T, Mersha, A, Mestrovic, T, Mettananda, K, Mettananda, S, Michalek, I, Miller, P, Miller, T, Mills, E, Minh, L, Mirijello, A, Mirrakhimov, E, Mirutse, M, Mirza-Aghazadeh-Attari, M, Mirzaei, M, Mirzaei, R, Misganaw, A, Mishra, A, Mitchell, P, Mittal, C, Moazen, B, Moberg, M, Mohamed, J, Mohamed, M, Mohamed, N, Mohammadi, E, Mohammadi, S, Mohammed, H, Mohammed, S, Mohr, R, Mokdad, A, Molinaro, S, Momtazmanesh, S, Monasta, L, Mondello, S, Moodi Ghalibaf, A, Moradi, M, Moradi, Y, Moradi-Lakeh, M, Moraga, P, Morawska, L, Moreira, R, Morovatdar, N, Morrison, S, Morze, J, Mosapour, A, Mosser, J, Mossialos, E, Motappa, R, Mougin, V, Mouodi, S, Mrejen, M, Msherghi, A, Mubarik, S, Mueller, U, Mulita, F, Munjal, K, Murillo-Zamora, E, Murlimanju, B, Mustafa, G, Muthu, S, Muzaffar, M, Myung, W, Nagarajan, A, Naghavi, P, Naik, G, Nainu, F, Nair, S, Najmuldeen, H, Nangia, V, Naqvi, A, Narayana, A, Nargus, S, Nascimento, G, Nashwan, A, Nasrollahizadeh, A, Natto, Z, Nayak, B, Nayak, V, Nduaguba, S, Negash, H, Negoi, I, Negoi, R, Nejadghaderi, S, Nesbit, O, Netsere, H, Ng, M, Nguefack-Tsague, G, Ngunjiri, J, Nguyen, D, Nguyen, H, Niazi, R, Nikolouzakis, T, Nikoobar, A, Nikoomanesh, F, Nikpoor, A, Nnaji, C, Nnyanzi, L, Noman, E, Nomura, S, Norrving, B, Nri-Ezedi, C, Ntaios, G, Ntsekhe, M, Nurrika, D, Nzoputam, C, Nzoputam, O, Oancea, B, Odetokun, I, O'Donnell, M, Oguntade, A, Oguta, J, Okati-Aliabad, H, Okeke, S, Okekunle, A, Okonji, O, Olagunju, A, Olasupo, O, Olatubi, M, Oliveira, G, Olufadewa, I, Olusanya, B, Olusanya, J, Omar, H, Omer, G, Omonisi, A, Onie, S, Onwujekwe, O, Ordak, M, Orish, V, Ortega-Altamirano, D, Ortiz, A, Ortiz-Brizuela, E, Osman, W, Ostroff, S, Osuagwu, U, Otoiu, A, Otstavnov, N, Otstavnov, S, Ouyahia, A, Ouyang, G, Owolabi, M, P A, M, Padron-Monedero, A, Padubidri, J, Palicz, T, Palladino, C, Pan, F, Pandi-Perumal, S, Pangaribuan, H, Panos, G, Panos, L, Pantea Stoian, A, Pardhan, S, Parikh, R, Pashaei, A, Pasovic, M, Passera, R, Patel, J, Patel, S, Patil, S, Patoulias, D, Patthipati, V, Pawar, S, Pazoki Toroudi, H, Pease, S, Peden, A, Pedersini, P, Peng, M, Pensato, U, Pepito, V, Peprah, E, Peprah, P, Perdigão, J, Pereira, M, Perianayagam, A, Perico, N, Pesudovs, K, Petermann-Rocha, F, Petri, W, Pham, H, Philip, A, Phillips, M, Pigeolet, M, Pigott, D, Pillay, J, Piracha, Z, Pirouzpanah, S, Plass, D, Plotnikov, E, Poddighe, D, Polinder, S, Postma, M, Pourtaheri, N, Prada, S, Pradhan, P, Prakash, V, Prasad, M, Prates, E, Priscilla, T, Pritchett, N, Puri, P, Puvvula, J, Qasim, N, Qattea, I, Qazi, A, Qian, G, Rabiee Rad, M, Radhakrishnan, R, Radhakrishnan, V, Raeisi Shahraki, H, Rafferty, Q, Raggi, A, Raghav, P, Rahim, M, Rahman, M, Rahmani, S, Rahmanian, M, Rahmawaty, S, Rajaa, S, Ramadan, M, Ramasamy, S, Ramasubramani, P, Ramazanu, S, Rana, K, Ranabhat, C, Rancic, N, Rane, A, Rao, C, Rao, K, Rao, M, Rao, S, Rashidi, M, Rathnaiah Babu, G, Rauniyar, S, Rawaf, D, Rawaf, S, Razo, C, Reddy, M, Redwan, E, Reifels, L, Reiner Jr, R, Remuzzi, G, Renzaho, A, Reshmi, B, Reyes, L, Rezaei, N, Rezaei Hachesu, P, Rezaeian, M, Rickard, J, Rodrigues, C, Rodriguez, J, Roever, L, Ronfani, L, Roshandel, G, Rotimi, K, Rout, H, Roy, B, Roy, N, Roy, P, Rubagotti, E, S N, C, Saad, A, Saber-Ayad, M, Sabour, S, Sacco, S, Sachdev, P, Saddik, B, Saddler, A, Sadee, B, Sadeghi, E, Sadeghi, M, Saeb, M, Saeed, U, Safi, S, Sagar, R, Sagoe, D, Saif, Z, Sajid, M, Sakshaug, J, Salam, N, Salami, A, Salaroli, L, Saleh, M, Salem, M, Sallam, M, Samadzadeh, S, Samargandy, S, Samodra, Y, Samy, A, Sanabria, J, Sanna, F, Santos, I, Santric-Milicevic, M, Sarasmita, M, Sarikhani, Y, Sarmiento-Suárez, R, Sarode, G, Sarode, S, Sarveazad, A, Sathian, B, Sathyanarayan, A, Satpathy, M, Sawhney, M, Scarmeas, N, Schaarschmidt, B, Schmidt, M, Schneider, I, Schumacher, A, Schwebel, D, Schwendicke, F, Sedighi, M, Senapati, S, Senthilkumaran, S, Sepanlou, S, Sethi, Y, Setoguchi, S, Seylani, A, Shadid, J, Shafie, M, Shah, H, Shah, N, Shah, P, Shahbandi, A, Shahid, S, Shahid, W, Shahwan, M, Shaikh, M, Shakeri, A, Shalash, A, Sham, S, Shamim, M, Shamshirgaran, M, Shamsi, M, Shanawaz, M, Shankar, A, Shannawaz, M, Sharath, M, Sharifan, A, Sharifi-Rad, J, Sharma, M, Sharma, R, Sharma, S, 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Sorensen, Reed J D, Soriano, Joan B, Soyiri, Ireneous N, Spartalis, Michael, Sreeramareddy, Chandrashekhar T, Stark, Benjamin A, Starodubova, Antonina V, Stein, Caroline, Stein, Dan J, Steiner, Caitlyn, Steiner, Timothy J, Steinmetz, Jaimie D, Steiropoulos, Paschalis, Stockfelt, Leo, Stokes, Mark A, Subedi, Narayan Subedi, Subramaniyan, Vetriselvan, Suemoto, Claudia Kimie, Suleman, Muhammad, Suliankatchi Abdulkader, Rizwan, Sultana, Abida, Sundström, Johan, Swain, Chandan Kumar, Szarpak, Lukasz, Tabaee Damavandi, Payam, Tabarés-Seisdedos, Rafael, Tabatabaei Malazy, Ozra, Tabatabaeizadeh, Seyed-Amir, Tabatabai, Shima, Tabche, Celine, Tabish, Mohammad, Tadakamadla, Santosh Kumar, Taheri Abkenar, Yasaman, Taheri Soodejani, Moslem, Taherkhani, Amir, Taiba, Jabeen, Talaat, Iman M, Talukder, Ashis, Tampa, Mircea, Tamuzi, Jacques Lukenze, Tan, Ker-Kan, Tandukar, Sarmila, Tang, Haosu, Tavakoli Oliaee, Razieh, Tavangar, Seyed Mohammad, Teimoori, Mojtaba, Temsah, Mohamad-Hani, Teramoto, Masayuki, Thangaraju, Pugazhenthan, Thankappan, Kavumpurathu Raman, Thapar, Rekha, Thayakaran, Rasiah, Thirunavukkarasu, Sathish, Thomas, Nihal, Thomas, Nikhil Kenny, Thum, Chern Choong Chern, Tichopad, Ales, Ticoalu, Jansje Henny Vera, Tillawi, Tala, Tiruye, Tenaw Yimer, Tobe-Gai, Ruoyan, Tonelli, Marcello, Topor-Madry, Roman, Torre, Anna E, Touvier, Mathilde, Tovani-Palone, Marcos Roberto, Tran, Jasmine T, Tran, Mai Thi Ngoc, Tran, Nghia Minh, Tran, Ngoc-Ha, Trico, Domenico, Tromans, Samuel Joseph, Truyen, Thien Tan Tri Tai, Tsatsakis, Aristidis, Tsegay, Guesh Mebrahtom, Tsermpini, Evangelia Eirini, Tumurkhuu, Munkhtuya, Tyrovolas, Stefanos, Udoh, Arit, Umair, Muhammad, Umakanthan, Srikanth, Umar, Tungki Pratama, Undurraga, Eduardo A, Unim, Brigid, Unnikrishnan, Bhaskaran, Unsworth, Carolyn Anne, Upadhyay, Era, Urso, Daniele, Usman, Jibrin Sammani, Vahabi, Seyed Mohammad, Vaithinathan, Asokan Govindaraj, Van den Eynde, Jef, Varga, Orsolya, Varma, Ravi Prasad, Vart, Priya, Vasankari, Tommi Juhani, Vasic, Milena, Vaziri, Siavash, Vellingiri, Balachandar, Venketasubramanian, Narayanaswamy, Veroux, Massimiliano, Verras, Georgios-Ioannis, Vervoort, Dominique, Villafañe, Jorge Hugo, Violante, Francesco S, Vlassov, Vasily, Vollset, Stein Emil, Volovat, Simona Ruxandra, Vongpradith, Avina, Waheed, Yasir, Wang, Cong, Wang, Fang, Wang, Ning, Wang, Shu, Wang, Yanzhong, Wang, Yuan-Pang, Ward, Paul, Wassie, Emebet Gashaw, Weaver, Marcia R, Weerakoon, Kosala Gayan, Weintraub, Robert G, Weiss, Daniel J, Weldemariam, Abrha Hailay, Wells, Katherine M, Wen, Yi Feng, Whisnant, Joanna L, Whiteford, Harvey A, Wiangkham, Taweewat, Wickramasinghe, Dakshitha Praneeth, Wickramasinghe, Nuwan Darshana, Wilandika, Angga, Wilkerson, Caroline, Willeit, Peter, Wimo, Anders, Woldegebreal, Demewoz H, Wolf, Axel Walter, Wong, Yen Jun, Woolf, Anthony D, Wu, Chenkai, Wu, Felicia, Wu, Xinsheng, Wu, Zenghong, Wulf Hanson, Sarah, Xia, Yanjie, Xiao, Hong, Xu, Xiaoyue, Xu, Yvonne Yiru, Yadav, Lalit, Yadollahpour, Ali, Yaghoubi, Sajad, Yamagishi, Kazumasa, Yang, Lin, Yano, Yuichiro, Yao, Yao, Yaribeygi, Habib, Yazdanpanah, Mohammad Hosein, Ye, Pengpeng, Yehualashet, Sisay Shewasinad, Yesuf, Subah Abderehim, Yezli, Saber, Yiğit, Arzu, Yiğit, Vahit, Yigzaw, Zeamanuel Anteneh, Yismaw, Yazachew, Yon, Dong Keon, Yonemoto, Naohiro, Younis, Mustafa Z, Yu, Chuanhua, Yu, Yong, Yusuf, Hadiza, Zahid, Mondal Hasan, Zakham, Fathiah, Zaki, Leila, Zaki, Nazar, Zaman, Burhan Abdullah, Zamora, Nelson, Zand, Ramin, Zandieh, Ghazal G Z, Zar, Heather J, Zarrintan, Armin, Zastrozhin, Mikhail Sergeevich, Zhang, Haijun, Zhang, Ning, Zhang, Yunquan, Zhao, Hanqing, Zhong, Chenwen, Zhong, Panliang, Zhou, Juexiao, Zhu, Zhaohua, Ziafati, Makan, Zielińska, Magdalena, Zimsen, Stephanie R M, Zoladl, Mohammad, Zumla, Alimuddin, Zyoud, Samer H, Vos, Theo, and Murray, Christopher J L
Abstract: Background: Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-based interventions that enable public health researchers, policy makers, and other professionals to implement strategies that can mitigate diseases. It can also facilitate more rigorous monitoring of progress towards national and international health targets, such as the Sustainable Development Goals. For three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has filled that need. A global network of collaborators contributed to the production of GBD 2021 by providing, reviewing, and analysing all available data. GBD estimates are updated routinely with additional data and refined analytical methods. GBD 2021 presents, for the first time, estimates of health loss due to the COVID-19 pandemic. Methods: The GBD 2021 disease and injury burden analysis estimated years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries using 100 983 data sources. Data were extracted from vital registration systems, verbal autopsies, censuses, household surveys, disease-specific registries, health service contact data, and other sources. YLDs were calculated by multiplying cause-age-sex-location-year-specific prevalence of sequelae by their respective disability weights, for each disease and injury. YLLs were calculated by multiplying cause-age-sex-location-year-specific deaths by the standard life expectancy at the age that death occurred. DALYs were calculated by summing YLDs and YLLs. HALE estimates were produced using YLDs per capita and age-specific mortality rates by location, age, sex, year, and cause.
Published: 2024

3. Follow-up von mehr als 250 radikalen Roboter-assistierten Zystektomien – eine unizentrische, prospektive Analyse

Author: Mohr, R, Siemer, S, Stöckle, M, Zeuschner, P, and Saar, M
Subjects: ddc: 610, Medicine and health
Abstract: Einleitung: Die Roboter-assistierte radikale Zystektomie (RARC) ist ein inzwischen etabliertes Verfahren in der Behandlung des muskelinvasiven Urothelkarzinoms (UCC) in high-volume Zentren, es existieren jedoch wenige Daten zum Langzeit Follow-up. Methode: Alle RARC von 01/2007 bis 12/2019 [zum vollständigen Text gelangen Sie über die oben angegebene URL]
Published: 2022
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4. Dataset of a retrospective multicenter cohort study on characteristics of immune checkpoint inhibitor-induced encephalitis and comparison with HSV-1 and anti-LGI1 encephalitis.

Author: Müller-Jensen, L, Zierold, S, Versluis, JM, Boehmerle, W, Huehnchen, P, Endres, M, Mohr, R, Compter, A, Blank, CU, Hagenacker, T, Meier, F, Reinhardt, L, Gesierich, A, Salzmann, M, Hassel, JC, Ugurel, S, Zimmer, L, Banks, P, Spain, L, Soon, JA, Enokida, T, Tahara, M, Kähler, KC, Seggewiss-Bernhardt, R, Harvey, C, Long, GV, Schöberl, F, von Baumgarten, L, Hundsberger, T, Schlaak, M, French, LE, Knauss, S, Heinzerling, LM, Müller-Jensen, L, Zierold, S, Versluis, JM, Boehmerle, W, Huehnchen, P, Endres, M, Mohr, R, Compter, A, Blank, CU, Hagenacker, T, Meier, F, Reinhardt, L, Gesierich, A, Salzmann, M, Hassel, JC, Ugurel, S, Zimmer, L, Banks, P, Spain, L, Soon, JA, Enokida, T, Tahara, M, Kähler, KC, Seggewiss-Bernhardt, R, Harvey, C, Long, GV, Schöberl, F, von Baumgarten, L, Hundsberger, T, Schlaak, M, French, LE, Knauss, S, and Heinzerling, LM
Abstract: Over the past decade, cancer immunotherapy with immune checkpoint inhibitors (ICIs) has significantly improved the outcome of many malignancies. However, with the broad use of ICIs, neurological immune related adverse events (irAE) are increasingly recognized. ICI-induced encephalitis (ICI-iE) is a particularly severe irAE, often leading to treatment termination, long-term sequalae or death. Despite its high morbidity and mortality, data on clinical features and diagnostic criteria are limited. We aimed to define clinical, radiologic and laboratory characteristics of ICI-iE and identify factors that discriminate it from anti-leucine-rich glioma-inactivated (anti-LGI)-1 encephalitis and herpes simplex virus (HSV)-1 encephalitis - two alternative causes of encephalitis - to increase the awareness of ICI-iE and improve its diagnosis and management. To that end, we retrospectively collected 30 cases of ICI-iE that were reported to the Side Effect Registry Immuno-Oncology (SERIO) and 46 cases of anti-LGI1 encephalitis or herpes simplex virus (HSV)-1 encephalitis that presented to a large German neurological referral center (Charité Universitätsmedizin Berlin) between January 2015 and September 2021. Signs and symptoms, imaging and electroencephalogram features, laboratory findings and outcome measures were assessed using standardized case report forms as well as patients' medical records and compared between the groups. The data reported here represents the largest primary cohort of patients with ICI-iE to date and the first comparison with other types of encephalitis. As all three disorders - ICI-iE, HSV-1 encephalitis and anti-LGI1 encephalitis - are rare neurological entities, this dataset can be used as a reference in future clinical studies on ICI-induced neurotoxicity, neurological autoimmune disorders, and central nervous system infections.
Published: 2022

5. The Women of Cathedral Oaks

Author: Mohr, Richard D.
Published: 2022

6. Contents

Author: Mohr, Richard D.
Published: 2022

7. Half Title Page

Author: Mohr, Richard D.
Published: 2022

8. Half Title Page, Title Page, Copyright, Dedication, Series Page

Author: Mohr, Richard D.
Published: 2022

9. Illustrations

Author: Mohr, Richard D.
Published: 2022

10. The Men of Cathedral Oaks

Author: Mohr, Richard D.
Published: 2022

11. Introduction: An Art School in the Mountains

Author: Mohr, Richard D.
Published: 2022

12. Coda: The School's Last Two Years and the Boys' Last Fifty — In Brief

Author: Mohr, Richard D.
Published: 2022

13. The Art of Cathedral Oaks

Author: Mohr, Richard D.
Published: 2022

14. Appendix: The Dates of the Tiles Explained

Author: Mohr, Richard D.
Published: 2022

15. The Arts and Crafts Principles of Cathedral Oaks

Author: Mohr, Richard D.
Published: 2022

16. Acknowledgments

Author: Mohr, Richard D.
Published: 2022

17. Notes

Author: Mohr, Richard D.
Published: 2022

18. Seed size and seeding rate effects on canola emergence, development, yield and seed weight.

Author: Harker, K. N., O'Donovan, J. T., Smith, E. G., Johnson, E. N., Peng, G., Willenborg, C. J., Gulden, R. H., Mohr, R., Gill, K. S., and Grenkow, L. A.
Subjects: SEED size, CANOLA, PLANT biomass, HERBICIDE resistance, WEEDS, SEED yield
Abstract: The article discusses direct-seeded experiments made on canola at several locations in Canada and mentions increased crop biomass due to increased seeding rates. Topics discussed include crop competition with weeds increased by biomass from large seeds, concerns of canola producers due to input costs and increased size of canola seed.
Published: 2022

19. Extracellular NAD + response to post-hepatectomy liver failure: bridging preclinical and clinical findings.

Author: Kamali C, Brunnbauer P, Kamali K, Saqr AA, Arnold A, Harman Kamali G, Babigian J, Keshi E, Mohr R, Felsenstein M, Moosburner S, Hillebrandt KH, Bartels J, Sauer IM, Tacke F, Schmelzle M, Pratschke J, and Krenzien F
Subjects: Animals, Humans, Mice, Male, Hepatocytes metabolism, Middle Aged, Female, Mice, Inbred C57BL, Liver Cirrhosis metabolism, Liver Cirrhosis surgery, Disease Models, Animal, Aged, NAD metabolism, Hepatectomy, Liver Failure etiology, Liver Failure metabolism, Liver Failure pathology, Liver Failure surgery
Abstract: Liver fibrosis progressing to cirrhosis is a major risk factor for liver cancer, impacting surgical treatment and survival. Our study focuses on the role of extracellular nicotinamide adenine dinucleotide (eNAD + ) in liver fibrosis, analyzing liver disease patients undergoing surgery. Additionally, we explore NAD + 's therapeutic potential in a mouse model of extended liver resection and in vitro using 3D hepatocyte spheroids. eNAD + correlated with aspartate transaminase (AST) and bilirubin after liver resection (AST: r = 0.2828, p = 0.0087; Bilirubin: r = 0.2584, p = 0.0176). Concordantly, post-hepatectomy liver failure (PHLF) was associated with higher eNAD + peaks (n = 10; p = 0.0063). Post-operative eNAD + levels decreased significantly (p < 0.05), but in advanced stages of liver fibrosis or cirrhosis, this decline not only diminished but actually showed a trend towards an increase. The expression of NAD + biosynthesis rate-limiting enzymes, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase 3 (NMNAT3), were upregulated significantly in the liver tissue of patients with higher liver fibrosis stages (p < 0.0001). Finally, the administration of NAD + in a 3D hepatocyte spheroid model rescued hepatocytes from TNFalpha-induced cell death and improved viability (p < 0.0001). In a mouse model of extended liver resection, NAD + treatment significantly improved survival (p = 0.0158) and liver regeneration (p = 0.0186). Our findings reveal that eNAD + was upregulated in PHLF, and rate-limiting enzymes of NAD + biosynthesis demonstrated higher expressions under liver fibrosis. Further, eNAD + administration improved survival after extended liver resection in mice and enhanced hepatocyte viability in vitro. These insights may offer a potential target for future therapies., (© 2024. The Author(s).)
Published: 2024
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20. Letter: Presence of progression or absence of response? Alternative trial designs for immunotherapy of advanced hepatocellular carcinoma. Authors' reply.

Author: Mohr R, Tacke F, and Roderburg C
Subjects: Humans, Research Design, Clinical Trials as Topic, Carcinoma, Hepatocellular therapy, Liver Neoplasms therapy, Immunotherapy methods, Disease Progression
Published: 2024
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21. Immune-related adverse effects: Recognition and initiation of appropriate treatment in cancer patients on immunotherapy.

Author: Mohr R, Howard A, and Townsend M
Abstract: Purpose: Delayed or improper identification of immune-related adverse events (IRAEs) during cancer treatment can impact time to receive proper treatment. This study describes rates of IRAE recognition and appropriate treatment in adult patients with cancer at a community teaching hospital., Methods: This single-center, retrospective, cohort study evaluated rates of proper IRAE treatment in conjunction with National Comprehensive Cancer Network (NCCN) guidelines. Secondary outcomes included time from presentation to IRAE diagnosis and hospital readmissions/repeat emergency department (ED) visits following initial admission for IRAE. Retrospective chart review assessed IRAE presentation including common terminology criteria for adverse event (CTCAE) grading and treatment choices., Results: Fifteen subjects included in this study contributed to 21 encounters with noted IRAE. Over half (52.4%) of the encounters received proper IRAE treatment (e.g. correct drug, dose, route, frequency, or therapy duration). Nearly 22% of total actionable components were improper, occurring more often in patients with colitis, pneumonitis, and hepatitis. Median time to IRAE diagnosis was approximately 3.5 days, with the longest being 24 days. There were eight all-cause rehospitalizations one year after initial IRAE presentation, with four directly IRAE-related. Most (75%) IRAE-related rehospitalizations occurred with colitis. Seven ED return visits were also noted., Conclusion: Many IRAEs were misdiagnosed and/or received improper treatment resulting in increased rehospitalization/return ED visit rates. The importance of medical oncology involvement (e.g. medical oncology consult at time of admission and/or notification of primary oncologist) in IRAE management in the hospital or ED was also stressed. Organizations may benefit from systematic improvements and staff education to improve patient outcomes and prevent readmissions., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Published: 2024
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22. A Koopman operator-based prediction algorithm and its application to COVID-19 pandemic and influenza cases.

Author: Mezić I, Drmač Z, Črnjarić N, Maćešić S, Fonoberova M, Mohr R, Avila AM, Manojlović I, and Andrejčuk A
Subjects: Humans, Pandemics, Algorithms, Nonlinear Dynamics, Influenza, Human epidemiology, COVID-19 epidemiology
Abstract: Future state prediction for nonlinear dynamical systems is a challenging task. Classical prediction theory is based on a, typically long, sequence of prior observations and is rooted in assumptions on statistical stationarity of the underlying stochastic process. These algorithms have trouble predicting chaotic dynamics, "Black Swans" (events which have never previously been seen in the observed data), or systems where the underlying driving process fundamentally changes. In this paper we develop (1) a global and local prediction algorithm that can handle these types of systems, (2) a method of switching between local and global prediction, and (3) a retouching method that tracks what predictions would have been if the underlying dynamics had not changed and uses these predictions when the underlying process reverts back to the original dynamics. The methodology is rooted in Koopman operator theory from dynamical systems. An advantage is that it is model-free, purely data-driven and adapts organically to changes in the system. While we showcase the algorithms on predicting the number of infected cases for COVID-19 and influenza cases, we emphasize that this is a general prediction methodology that has applications far outside of epidemiology., (© 2024. The Author(s).)
Published: 2024
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23. Soluble urokinase plasminogen activator receptor levels predict survival in patients with portal hypertension undergoing TIPS.

Author: Loosen SH, Benz F, Mohr R, Reuken PA, Wirtz TH, Junker L, Jansen C, Meyer C, Praktiknjo M, Wree A, Reißing J, Demir M, Gu W, Vucur M, Schierwagen R, Stallmach A, Kunstein A, Bode J, Trautwein C, Tacke F, Luedde T, Bruns T, Trebicka J, and Roderburg C
Abstract: Background & Aims: Transjugular intrahepatic portosystemic shunt (TIPS) is the most effective therapy for complications of portal hypertension. However, clinical outcomes following TIPS placement vary widely between patients and identifying ideal candidates remains a challenge. Soluble urokinase plasminogen activator receptor (suPAR) is a circulating marker of immune activation that has previously been associated with liver inflammation, but its prognostic value in patients receiving TIPS is unknown. In the present study, we evaluated the potential clinical relevance of suPAR levels in patients undergoing TIPS insertion., Methods: suPAR concentrations were measured by ELISA in hepatic vein (HV) and portal vein (PV) blood samples from 99 patients (training cohort) as well as peripheral venous blood samples from an additional 150 patients (validation cohort) undergoing TIPS placement. The association between suPAR levels and patient outcomes was assessed using Kaplan-Meier methods and Cox-regression analyses., Results: suPAR concentrations were significantly higher in HV samples compared to PV samples and correlated with PV concentration, the presence of ascites, renal injury, and consequently with the Child-Pugh and MELD scores. Patients with lower suPAR levels had significantly better short- and long-term survival after TIPS insertion, which remained robust after adjustment for confounders in multivariate Cox-regression analyses. Sensitivity analysis showed an improvement in risk prediction in patients stratified by Child-Pugh or MELD scores. In an independent validation cohort, higher levels of suPAR predicted poor transplant-free survival after TIPS, particularly in patients with Child-Pugh A/B cirrhosis., Conclusion: suPAR is largely derived from the injured liver and its levels are predictive of outcome in patients undergoing TIPS. suPAR, as a surrogate of hepatic inflammation, may be used to stratify care in patients following TIPS insertion., Impact and Implications: Transjugular intrahepatic portosystemic shunt (TIPS) is the most effective therapy for complications of portal hypertension. However, clinical outcomes following TIPS placement vary widely between patients and identification of the ideal candidates remains challenging. We show that soluble urokinase plasminogen activator receptor (suPAR), a circulating marker of immune activation that can easily be measured in routine clinical practice, is a novel marker to identify patients who will benefit from TIPS and those who will not., Competing Interests: The authors declare that they have no competing interests related to this manuscript. S.H.L. has received honoraria for consulting or lectures from BMS and MSD. PA.R received lecture and consulting fees from CSL Behring, Pfizer, Gilead and BristolMyersQuipp and Boston Scientific. F.T.’s lab has received research funding from Allergan, Bristol-Myers Squibb, Gilead and Inventiva. F.T. has received honoraria for consulting or lectures from Astra Zeneca, Gilead, AbbVie, BMS, Boehringer, Madrigal, Intercept, Falk, Ionis, Inventiva, Merz, Pfizer, Alnylam, NGM, CSL Behring, Novo Nordisk, Novartis. T.B. received consulting fees from Intercept/Advanz Pharma, Grifols, and Sobi as well as honoraria for lectures, presentations, or educational events from Falk Foundation, CSL Behring, Merck, Gilead, Intercept/Advanz Pharma, and Gore. J.T. has received speaking and/or consulting fees from Versantis, Gore, Boehringer-Ingelheim, Falk, Grifols, Genfit and CSL Behring. C.R.ás lab has received research funding from Servier and LamKap Bio. C.R. has received honoraria for consulting or lectures from Amgen, Astra Zeneca, BMS, Deciphera, Esteve, Incyte, Ipsen, Novartis, MSD, Merck, Lilly, Pierre Fabre, Roche, Falk, Servier. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2024 The Author(s).)
Published: 2024
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24. Single versus bilateral internal thoracic artery grafting in patients with impaired renal function.

Author: Farkash A, Gordon A, Mohr R, Sela O, Pevni D, Ziv-Baran T, Grupper A, Kfir JE, and Ben-Gal Y
Subjects: Humans, Retrospective Studies, Treatment Outcome, Coronary Artery Bypass adverse effects, Kidney surgery, Risk Factors, Mammary Arteries transplantation, Coronary Artery Disease complications, Coronary Artery Disease surgery
Abstract: Objective: The optimal strategy for surgical revascularization in patients with impaired renal function is inconclusive. We compared early and late outcomes between bilateral internal thoracic artery (BITA) and single ITA (SITA) grafting in patients with renal dysfunction., Methods: This is a retrospective analysis of all the patients with multivessel disease and impaired renal function (estimated glomerular filtration rate <60mL/min/1.73m2) who underwent isolated coronary artery bypass graft (CABG) in our center during 1996-2011, utilizing either BITA or SITA revascularization., Results: Of the 5301 patients with multivessel disease who underwent surgical revascularization during the study period, 391 were with impaired renal function: 212 (54.2%) underwent BITA, 179 (45.8%) underwent SITA. Patients who underwent BITA were less likely to have comorbidities. Statistically significant differences were not observed between the BITA and SITA groups in 30-day mortality (5.6% vs. 9.0%, p = 0.2) and in rates of early stroke, myocardial infarction, and sternal infection (4.5% vs. 6.1%, p = 0.467; 1.7% vs. 2.8%, p = 0.517; and 2.2% vs. 5.7%, p = 0.088, respectively). Long-term survival of the BITA group was better: median 8.36 vs. 4.14 years, p<0.001. In multivariable analysis, BITA revascularization was associated with decreased late mortality (HR = 0.704, 95% CI: 0.556-0.89, p = 0.003). In analysis of a matched cohort (134 pairs), early outcomes did not differ between the groups; however, in multivariable analysis, BITA revascularization was associated with decreased late mortality ‎‎(HR = 0.35 (95%CI 0.18-0.68), p = 0.002)‎., Conclusions: BITA revascularization did not impact early outcome in patients with CRF, but demonstrated a significant protective effect on long-term survival ‎in the unmatched and matched cohorts., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Farkash et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Published: 2024
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25. Immune signatures of checkpoint inhibitor-induced autoimmunity-A focus on neurotoxicity.

Author: Müller-Jensen L, Schulz AR, Mei HE, Mohr R, Ulrich C, Knape P, Frost N, Frischbutter S, Kunkel D, Schinke C, Ginesta Roque L, Maierhof SK, Nickel FT, Heinzerling L, Endres M, Boehmerle W, Huehnchen P, and Knauss S
Subjects: Humans, Acute Disease, Autoimmunity, Ligands, Retrospective Studies, Lung Neoplasms, Melanoma
Abstract: Background: Neurologic immune-related adverse events (irAE-n) are rare but severe toxicities of immune checkpoint inhibitor (ICI) treatment. To overcome diagnostic and therapeutic challenges, a better mechanistic understanding of irAE-n is paramount., Methods: In this observational cohort study, we collected serum and peripheral blood samples from 34 consecutive cancer patients with irAE-n (during acute illness) and 49 cancer control patients without irAE-n (pre- and on-ICI treatment, n = 44 without high-grade irAEs, n = 5 with high-grade nonneurologic irAEs). Patients received either anti-programmed cell death protein (PD)-1 or anti-PD ligand-1 monotherapy or anti-PD-1/anti-cytotoxic T-lymphocyte-associated protein-4 combination therapy. Most common cancers were melanoma, lung cancer, and hepatocellular carcinoma. Peripheral blood immune profiling was performed using 48-marker single-cell mass cytometry and a multiplex cytokine assay., Results: During acute illness, patients with irAE-n presented higher frequencies of cluster of differentiation (CD)8+ effector memory type (EM-)1 and central memory (CM) T cells compared to controls without irAEs. Multiorgan immunotoxicities (neurologic + nonneurologic) were associated with higher CD8+ EM1 T cell counts. While there were no B cell changes in the overall cohort, we detected a marked decrease of IgD- CD11c+ CD21low and IgD- CD24+ CD21high B cells in a subgroup of patients with autoantibody-positive irAE-n. We further identified signatures indicative of enhanced chemotaxis and inflammation in irAE-n patients and discovered C-X-C motif chemokine ligand (CXCL)10 as a promising marker to diagnose high-grade immunotoxicities such as irAE-n., Conclusions: We demonstrate profound and partly subgroup-specific immune cell dysregulation in irAE-n patients, which may guide future biomarker development and targeted treatment approaches., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Published: 2024
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26. Dataset for: Autoantibody profiles in patients with immune checkpoint inhibitor-induced neurological immune-related adverse events.

Author: Müller-Jensen L, Knauss S, Ginesta Roque L, Schinke C, Maierhof SK, Bartels F, Finke C, Rentzsch K, Ulrich C, Mohr R, Stenzel W, Endres M, Boehmerle W, and Huehnchen P
Abstract: The rise of cancer immunotherapy has been a milestone in clinical oncology. Above all, immune checkpoint inhibitor treatment (ICI) with monoclonal antibodies targeting programmed cell death protein 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) has improved survival rates for an increasing number of malignancies. However, despite the clinical benefits, ICI-related autoimmunity has become a significant cause of non-relapse-related morbidity and mortality. Neurological immune-related adverse events (irAE-n) are particularly severe toxicities with a high risk for chronic illness, long-term steroid dependency, and early ICI treatment termination. While the clinical characteristics of irAE-n are well described, little is known about underlying immune mechanisms and potential biomarkers. Recently, high frequencies of neuronal autoantibodies in patients with irAE-n have been reported, however, their clinical relevance is unclear. Here, we present a dataset on neuronal autoantibody profiles in ICI-treated cancer patients with and without irAE-n, which was generated to investigate the potential role of neuronal autoantibodies in ICI-induced autoimmunity. Between September 2017 and January 2022 serum samples of 29 cancer patients with irAE-n post-ICI treatment) and 44 cancer control patients without high-grade immune-related adverse events (irAEs, n = 44 pre- and post-ICI treatment) were collected and tested for a large panel of brain-reactive and neuromuscular autoantibodies using indirect immunofluorescence and immunoblot assays. Prevalence of autoantibodies was compared between the groups and correlated with clinical characteristics such as outcome and irAE-n manifestation. These data represent the first systematic comparison of neuronal autoantibody profiles between ICI-treated cancer patients with and without irAE-n, providing valuable information for both researchers and clinicians. In the future, this dataset may be valuable for meta-analyses on the prevalence of neuronal autoantibodies in cancer patients., (© 2024 The Author(s).)
Published: 2024
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27. Optimized protocol for quantification of extracellular nicotinamide adenine dinucleotide: evaluating clinical parameters and pre-analytical factors for translational research.

Author: Saqr AA, Kamali C, Brunnbauer P, Haep N, Koch P, Hillebrandt KH, Keshi E, Moosburner S, Mohr R, Raschzok N, Pratschke J, and Krenzien F
Abstract: Nicotinamide adenine dinucleotide (NAD + ), a coenzyme for more than 500 enzymes, plays a central role in energy production, metabolism, cellular signaling, and DNA repair. Until recently, NAD + was primarily considered to be an intracellular molecule (iNAD + ), however, its extracellular species (eNAD + ) has recently been discovered and has since been associated with a multitude of pathological conditions. Therefore, accurate quantification of eNAD + in bodily fluids such as plasma is paramount to answer important research questions. In order to create a clinically meaningful and reliable quantitation method, we analyzed the relationship of cell lysis, routine clinical laboratory parameters, blood collection techniques, and pre-analytical processing steps with measured plasma eNAD + concentrations. Initially, NAD + levels were assessed both intracellularly and extracellularly. Intriguingly, the concentration of eNAD + in plasma was found to be approximately 500 times lower than iNAD + in peripheral blood mononuclear cells (0.253 ± 0.02 μM vs. 131.8 ± 27.4 μM, p = 0.007, respectively). This stark contrast suggests that cellular damage or cell lysis could potentially affect the levels of eNAD + in plasma. However, systemic lactate dehydrogenase in patient plasma, a marker of cell damage, did not significantly correlate with eNAD + ( n = 33; r = -0.397; p = 0.102). Furthermore, eNAD + was negatively correlated with increasing c-reactive protein (CRP, n = 33; r = -0.451; p = 0.020), while eNAD + was positively correlated with increasing hemoglobin ( n = 33; r = 0.482; p = 0.005). Next, variations in blood drawing, sample handling and pre-analytical processes were examined. Sample storage durations at 4°C (0-120 min), temperature (0° to 25°C), cannula sizes for blood collection and tourniquet times (0 - 120 s) had no statistically significant effect on eNAD + ( p > 0.05). On the other hand, prolonged centrifugation (> 5 min) and a faster braking mode of the centrifuge rotor (< 4 min) resulted in a significant decrease in eNAD + levels ( p < 0.05). Taken together, CRP and hemoglobin appeared to be mildly correlated with eNAD + levels whereas cell damage was not correlated significantly to eNAD + levels. The blood drawing trial did not show any influence on eNAD + , in contrast, the preanalytical steps need to be standardized for accurate eNAD + measurement. This work paves the way towards robust eNAD + measurements, for use in future clinical and translational research, and provides an optimized hands-on protocol for reliable eNAD + quantification in plasma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Saqr, Kamali, Brunnbauer, Haep, Koch, Hillebrandt, Keshi, Moosburner, Mohr, Raschzok, Pratschke and Krenzien.)
Published: 2024
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28. Gd-EOB MRI for HCC subtype differentiation in a western population according to the 5 th edition of the World Health Organization classification.

Author: Auer TA, Halskov S, Fehrenbach U, Nevermann NF, Pelzer U, Mohr R, Hamm B, Schöning W, Horst D, Ihlow J, and Geisel D
Subjects: Humans, Female, Retrospective Studies, Gadolinium DTPA, Contrast Media pharmacology, Magnetic Resonance Imaging methods, Sensitivity and Specificity, Carcinoma, Hepatocellular pathology, Liver Neoplasms pathology, Diabetes Mellitus, Type 2, Fatty Liver
Abstract: Objectives: To investigate the value of gadoxetic acid (Gd-EOB)-enhanced magnetic resonance imaging (MRI) for noninvasive subtype differentiation of HCCs according to the 5 th edition of the WHO Classification of Digestive System Tumors in a western population., Methods: This retrospective study included 262 resected lesions in 240 patients with preoperative Gd-EOB-enhanced MRI. Subtypes were assigned by two pathologists. Gd-EOB-enhanced MRI datasets were assessed by two radiologists for qualitative and quantitative imaging features, including imaging features defined in LI-RADS v2018 and area of hepatobiliary phase (HBP) iso- to hyperintensity., Results: The combination of non-rim arterial phase hyperenhancement with non-peripheral portal venous washout was more common in "not otherwise specified" (nos-ST) (88/168, 52%) than other subtypes, in particular macrotrabecular massive (mt-ST) (3/15, 20%), chromophobe (ch-ST) (1/8, 13%), and scirrhous subtypes (sc-ST) (2/9, 22%) (p = 0.035). Macrovascular invasion was associated with mt-ST (5/16, p = 0.033) and intralesional steatosis with steatohepatitic subtype (sh-ST) (28/32, p < 0.001). Predominant iso- to hyperintensity in the HBP was only present in nos-ST (16/174), sh-ST (3/33), and clear cell subtypes (cc-ST) (3/13) (p = 0.031). Associations were found for the following non-imaging parameters: age and sex, as patients with fibrolamellar subtype (fib-ST) were younger (median 44 years (19-66), p < 0.001) and female (4/5, p = 0.023); logarithm of alpha-fetoprotein (AFP) was elevated in the mt-ST (median 397 µg/l (74-5370), p < 0.001); type II diabetes mellitus was more frequent in the sh-ST (20/33, p = 0.027)., Conclusions: Gd-EOB-MRI reproduces findings reported in the literature for extracellular contrast-enhanced MRI and CT and may be a valuable tool for noninvasive HCC subtype differentiation., Clinical Relevance Statement: Better characterization of the heterogeneous phenotypes of HCC according to the revised WHO classification potentially improves both diagnostic accuracy and the precision of therapeutic stratification for HCC., Key Points: • Previously reported imaging features of common subtypes in CT and MRI enhanced with extracellular contrast agents are reproducible with Gd-EOB-enhanced MRI. • While uncommon, predominant iso- to hyperintensity in the HBP was observed only in NOS, clear cell, and steatohepatitic subtypes. • Gd-EOB-enhanced MRI offers imaging features that are of value for HCC subtype differentiation according to the 5 th edition of the WHO Classification of Digestive System Tumors., (© 2023. The Author(s).)
Published: 2023
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29. Prediction of regional lymph node metastasis in intrahepatic cholangiocarcinoma: it's not all about size.

Author: Kolck J, Auer TA, Walter-Rittel T, Hosse C, Elkilany A, Marth AA, Pelzer U, Mohr R, Krenzien F, Lurje G, Schöning W, Hamm B, Geisel D, and Fehrenbach U
Subjects: Humans, Lymphatic Metastasis, Lymph Node Excision methods, Bile Ducts, Intrahepatic pathology, Prognosis, Retrospective Studies, Cholangiocarcinoma pathology, Bile Duct Neoplasms pathology
Abstract: Objectives: Lymph node metastases (LNM) are frequent in patients with intrahepatic cholangiocarcinoma (iCC) and worsen their prognosis even after surgery. Our aim was to investigate the predictive value of lymph node (LN) short axis, the most common discriminator for identifying LNM in tumor-imaging and to develop a predictive model for regional LNM in iCC taking computed tomography (CT) features of extranodal disease into account., Materials and Methods: We enrolled 102 patients with pathologically proven iCC who underwent CT prior to hepatic resection and hilar lymph node dissection (LND) from 2005 to 2021. Two blinded radiologists assessed various imaging characteristics and LN diameters, which were analyzed by bivariate and multivariate logistic regression to develop a prediction model for LNM., Results: Prevalence of LNM was high (42.4 %) and estimated survival was shorter in LN-positive patients (p = 0.07). An LN short axis diameter of ≥ 9 mm demonstrated the highest predictive power for LNM. Three additional, statistically significant imaging features, presence of intrahepatic metastasis (p = 0.003), hilar tumor infiltration (p = 0.003), and tumor growth along the liver capsule (p = 0.004), were integrated into a prediction model, which substantially outperformed use of LN axis alone in ROC analysis (AUC 0.856 vs 0.701)., Conclusions: LN diameter alone proved to be a relevant but unreliable imaging-marker for LNM prediction in iCC. Our proposed prognostic model, which additionally considers intrahepatic metastases and hilar and capsular infiltration, significantly improves discriminatory power. Hilar and capsular involvement might indicate direct tumor extension to lymphatic liver structures., (© 2023. The Author(s).)
Published: 2023
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30. Non-Alcoholic Fatty Liver Disease (NAFLD) and risk of new-onset heart failure: a retrospective analysis of 173,966 patients.

Author: Roderburg C, Krieg S, Krieg A, Vaghiri S, Mohr R, Konrad M, Luedde M, Luedde T, Kostev K, and Loosen SH
Subjects: Male, Humans, Female, Retrospective Studies, Risk Factors, Comorbidity, Non-alcoholic Fatty Liver Disease complications, Non-alcoholic Fatty Liver Disease diagnosis, Non-alcoholic Fatty Liver Disease epidemiology, Heart Failure diagnosis, Heart Failure epidemiology, Heart Failure complications
Abstract: Background: Non-alcoholic fatty liver disease (NAFLD) represents the leading cause of chronic liver disease. Its high mortality and morbidity are mainly caused by non-hepatic comorbidities and their clinical complications. Accumulating evidence suggests an association between NAFLD and heart failure (HF), but large-scale data analyses from Germany are scarce., Methods: Using the Disease Analyzer database (IQVIA), this analysis retrospectively evaluated two cohorts of outpatients with and without NAFLD with respect to the cumulative incidence of HF as the primary outcome between January 2005 and December 2020. Cohorts were propensity score matched for sex, age, index year, yearly consultation frequency, and known risk factors for HF., Results: A total of 173,966 patients were included in the analysis. Within 10 years of the index date, 13.2% vs. 10.0% of patients with and without NAFLD were newly diagnosed with HF (p < 0.001). This finding was supported by univariate Cox regression analysis in which NAFLD was found to be significantly associated with subsequent HF (Hazard Ratio (HR) 1.34, 95% Confidence Interval (CI) 1.28-1.39, p < 0.001). The association between NAFLD and HF was observed across all analysed age groups and as comparable between both men (HR 1.30, 95% CI 1.23-1.38; p < 0.001) and women (HR: 1.37, 95% CI 1.29-1.45; p < 0.001)., Conclusion: NAFLD is significantly associated with an increased cumulative incidence of HF, which, given its rapidly increasing global prevalence, could be crucial to further reduce its high mortality and morbidity. We recommend risk stratification within a multidisciplinary approach for NAFLD patients, including systematic prevention or early detection strategies for HF., (© 2023. The Author(s).)
Published: 2023
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31. Prevalence of and factors associated with a treatment delay due to the COVID-19 pandemic in patients with gastrointestinal cancer in Europe.

Author: Roderburg C, Loosen SH, Leyh C, Joerdens MS, Mohr R, Luedde T, Alymova S, Klein I, and Kostev K
Subjects: Humans, Pandemics, Time-to-Treatment, Prevalence, Cross-Sectional Studies, Retrospective Studies, Europe epidemiology, COVID-19 epidemiology, Gastrointestinal Neoplasms
Abstract: Background: Recent studies have raised the issue of delayed cancer care during the COVID-19 pandemic, but the extent of delays and cancellations in cancer treatment, screening and diagnosis varied widely by geographic region and study design, highlighting the need for further research., Methods: We used the Oncology Dynamics (OD) database featuring data from a cross-sectional, partially retrospective survey to analyze treatment delays in 30,171 GI cancer patients from five European countries (Germany, France, UK, Spain, and Italy). Risk factors for treatment delays were identified using multivariable logistic regression models., Results: Treatment delays were documented in 1342 (4.5%) of the study patients, with most patients having a delay of less than 3 months (3.2%). We observed decisive differences of treatment delay in relation to geographical, healthcare- and patient-related factors. Treatment delay was highest in France (6.7%) and Italy (6.5%) and lowest in Spain (1.9%, p < 0.001). 5.9% of patients treated at general hospitals but only 1.9% of those treated by office-based physicians experienced treatment delays (p < 0.001). Moreover, the difference between lines of therapy was highly significant and ranged from 7.2% for early-stage patients in primary therapy to 2.6% in advanced/metastatic cancer patients receiving 4th or later line therapy (p < 0.001). Finally, the proportion of cases with delayed treatments increased from 3.5% in asymptomatic patients (ECOG 0) to 9.9% in bedridden patients (ECOG IV, p < 0.001). Results were confirmed in multivariable logistic regression models. Our data highlight the problem of delayed treatment of tumor patients in the context of the COVID-19 pandemic. Identified risk factors for delayed treatment, such as poor general health or treatment in smaller hospitals, offer starting points for future concepts of "pandemic preparedness"., (© 2023. The Author(s).)
Published: 2023
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32. Osteopontin is a prognostic circulating biomarker in patients with neuroendocrine neoplasms.

Author: Kidess E, Giesecke Y, Eichhorn I, Mohr R, Jann H, Fischer C, Wiedenmann B, Roderburg C, Tacke F, and Sigal M
Subjects: Female, Humans, Male, Biomarkers, Tumor metabolism, Chromogranin A, Prognosis, Neuroendocrine Tumors pathology, Osteopontin metabolism
Abstract: Purpose: Osteopontin (OPN), also called secreted phosphoprotein 1 (SPP1) is a matricellular glycoprotein whose expression is elevated in various types of cancer and which has been shown to be involved in tumorigenesis and metastasis in many malignancies. Its role in neuroendocrine neoplasms (NEN) remains to be established. The aim of the study was to analyze plasma concentrations of OPN in patients with NEN and to explore its diagnostic and prognostic value as a clinical biomarker., Methods: OPN plasma concentrations were measured in a total of 38 patients with histologically proven NEN at three different time points during the course of disease and therapy (at the start of the study, after 3 and 12 months, respectively) as well as in healthy controls. Clinical and imaging data as well as concentrations of Chromogranin A (CgA) and Neuron Specific Enolase (NSE) were assessed., Results: OPN levels were significantly higher in patients with NEN compared to healthy controls. High-grade tumors (grade 3) showed the highest OPN levels. OPN levels were neither different between male and female patients nor between different primary tumor sites. OPN correlated significantly with corresponding NSE levels, while there was no correlation with Chromogranin A. High OPN levels above a cutoff value of 200 ng/ml at initial analysis predicted a worsened prognosis with significantly shorter progression-free survival of patients with NEN, which also held true within the subgroup of well-differentiated G1/G2 tumors., Conclusion: Our data indicate that high baseline OPN levels in patients with NEN are predictive of an adverse outcome with shorter progression-free survival, even within the group of well differentiated G1/G2 tumors. Therefore, OPN may be used as a surrogate prognostic biomarker in patients with NEN., (© 2023. The Author(s).)
Published: 2023
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33. The Role of Alternative Lymph Node Classification Systems in Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NEN): Superiority of a LODDS Scheme Over N Category in Pancreatic NEN (pNEN).

Author: Krieg S, Tunk J, Vaghiri S, Prassas D, Jann H, Mohr R, Loosen SH, Roderburg C, Maasberg S, Begum N, Luedde T, Schott M, Giesel F, Knoefel WT, and Krieg A
Subjects: Humans, Neoplasm Staging, Lymph Nodes pathology, Prognosis, Gastrointestinal Neoplasms pathology, Neuroendocrine Tumors surgery, Neuroendocrine Tumors pathology, Pancreatic Neoplasms surgery, Pancreatic Neoplasms pathology
Abstract: Lymph node (LN) involvement in gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) has been reported to have prognostic and therapeutic implications. Numerous novel LN classifications exist; however, no comparison of their prognostic performance for GEP-NEN has been done yet. Using a nationwide cohort from the German Neuroendocrine Tumor (NET) Registry, the prognostic and discriminatory power of different LN ratio (LNR) and log odds of metastatic LN (LODDS) classifications were investigated using multivariate Cox regression and C-statistics in 671 patients with resected GEP-NEN. An increase in positive LN (pLN), LNR, and LODDS was associated with advanced tumor stages, distant metastases, and hormonal functionality. However, none of the alternative LN classifications studied showed discriminatory superiority in predicting prognosis over the currently used N category. Interestingly, in a subgroup analysis, one LODDS classification was identified that might be most appropriate for patients with pancreatic NEN (pNEN). On this basis, a nomogram was constructed to estimate the prognosis of pNEN patients after surgery. In conclusion, a more accurate classification of LN status may allow a more precise prediction of overall survival and provide the basis for individualized strategies for postoperative treatment and surveillance especially for patients with pNEN., Competing Interests: The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)
Published: 2023
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34. Systemic treatment in patients with Child-Pugh B liver dysfunction and advanced hepatocellular carcinoma.

Author: Costa F, Wiedenmann B, Roderburg C, Mohr R, and Abou-Alfa GK
Subjects: Humans, Randomized Controlled Trials as Topic, Antineoplastic Agents therapeutic use, Carcinoma, Hepatocellular complications, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms complications, Liver Neoplasms drug therapy
Abstract: Hepatocellular carcinoma (HCC) is a major cause of death among patients with liver cirrhosis. The rise of immuno-oncology has revolutionized treatment for advanced HCC. However, most pivotal randomized controlled trials have excluded patients with moderate liver dysfunction (Child-Pugh-Turcotte B), despite the high incidence of liver disease in patients with HCC at the time of diagnosis. Overall survival in patients with HCC and moderate liver dysfunction treated with sorafenib has been found to be only approximately 3-5 months, underlining the need for improved treatment algorithms for this increasingly important subgroup of patients. In this review, we summarize available data on the treatment of patients with HCC and moderate liver dysfunction. Opportunities, as well as clinical challenges, are discussed in detail, highlighting potential changes to the therapeutic landscape., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
Published: 2023
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35. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma: Results from a German real-world cohort.

Author: Jost-Brinkmann F, Demir M, Wree A, Luedde T, Loosen SH, Müller T, Tacke F, Roderburg C, and Mohr R
Subjects: Humans, Bevacizumab adverse effects, Antibodies, Monoclonal, Humanized adverse effects, Liver Cirrhosis drug therapy, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy
Abstract: Background and Aims: Phase III trials have established atezolizumab plus bevacizumab as the novel standard of care for patients with unresectable hepatocellular carcinoma (HCC). However, these trials raised concerns regarding treatment efficacy in non-viral HCC, and it remains unclear whether combination immunotherapy is safe and effective in patients with advanced cirrhosis., Methods: One hundred patients with unresectable HCC initiated therapy with atezolizumab plus bevacizumab at our centre between January 2020 and March 2022. The control cohort consisted of 80 patients with advanced HCC who received either sorafenib (n = 43) or lenvatinib (n = 37) as systemic treatment., Results: Overall survival (OS) and progression-free survival (PFS) were significantly longer within the atezolizumab/bevacizumab group and comparable to phase III data. The benefits in terms of increased objective response rate (ORR), OS and PFS were consistent across subgroups, including non-viral HCC (58%). The ROC-optimised neutrophil-to-lymphocyte ratio (NLR) cut-off of 3.20 was the strongest independent predictor of ORR and PFS. In patients with advanced cirrhosis Child-Pugh B, liver function was significantly better preserved with immunotherapy. Patients with Child-Pugh B cirrhosis showed similar ORR but shorter OS and PFS compared to patients with preserved liver function., Conclusions: Atezolizumab plus bevacizumab showed good efficacy and safety in patients with unresectable HCC and partially advanced liver cirrhosis in a real-world setting. Moreover, the NLR was able to predict response to atezolizumab/bevacizumab treatment and may guide patient selection., (© 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)
Published: 2023
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36. Study protocol of an open-label, single arm phase II trial investigating the efficacy and safety of Trifluridine/Tipiracil combined with irinotecan as a second line therapy in patients with cholangiocarcinoma (TRITICC).

Author: Kehmann L, Berres ML, Gonzalez-Carmona M, Modest DP, Mohr R, Wree A, Venerito M, Strassburg C, Keitel V, Trautwein C, Luedde T, and Roderburg C
Subjects: Adult, Humans, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bile Ducts, Intrahepatic pathology, Cisplatin, Clinical Trials, Phase II as Topic, Deoxycytidine, Disease Progression, Gemcitabine, Irinotecan, Prospective Studies, Trifluridine adverse effects, Multicenter Studies as Topic, Bile Duct Neoplasms drug therapy, Bile Duct Neoplasms etiology, Biliary Tract Neoplasms drug therapy, Cholangiocarcinoma drug therapy, Cholangiocarcinoma etiology, Colorectal Neoplasms pathology, Frontotemporal Dementia chemically induced, Frontotemporal Dementia drug therapy
Abstract: Background: The prognosis of patients with advanced biliary tract cancer (BTC) who have progressed on gemcitabine plus cisplatin is dismal. Trifluridine/tipiracil (FTD/TPI) and irinotecan have proven efficacy in different gastrointestinal malignancies. We therefore hypothesized that this combination might improve the therapeutic outcome in patients with BTC after failure of first line treatment., Methods: TRITICC is an interventional, prospective, open-label, non-randomised, exploratory, multicentre, single-arm phase IIA clinical trial done in 6 sites with expertise in managing biliary tract cancer across Germany. A total of 28 adult patients (aged ≥ 18 years) with histologically verified locally advanced or metastatic biliary tract cancer (including cholangiocarcinoma and gallbladder or ampullary carcinoma) with documented radiological disease progression to first-line gemcitabine based chemotherapy will be included to receive a combination of FTD/TPI plus irinotecan according to previously published protocols. Study treatment will be continued until disease progression according to RECIST 1.1 criteria or occurrence of unacceptable toxicity. The effect of FTD/TPI plus irinotecan on progression-free survival will be analyzed as primary endpoint. Safety (according to NCI-CTCAE), response rates and overall survival are secondary endpoints. In addition, a comprehensive translational research program is part of the study and might provide findings about predictive markers with regard to response, survival periods and resistance to treatment., Discussion: The aim of TRITICC is to evaluate the safety and efficacy of FTD/TPI plus irinotecan in patients with biliary tract cancer refractory to previous Gemcitabine based treatment., Trial Registration: EudraCT 2018-002936-26; NCT04059562., (© 2023. The Author(s).)
Published: 2023
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37. Interventional Treatment Strategies in Intrahepatic Cholangiocarcinoma and Perspectives for Combined Hepatocellular-Cholangiocarcinoma.

Author: Auer TA, Collettini F, Segger L, Pelzer U, Mohr R, Krenzien F, Gebauer B, Geisel D, Hosse C, Schöning W, and Fehrenbach U
Abstract: cHCC-CCA is an uncommon type of liver cancer that exhibits clinical and pathological characteristics of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), which are the two main forms of primary liver cancer. The similarity to HCC and CCA makes therapeutical strategies challenging. The poor prognosis of CCA in general, as well as for cHCC-CCA, is mainly attributable to the fact that diagnosis is often at an advanced stage of disease. During the last decade, locoregional therapies usually performed by interventional radiologists and its established role in HCC treatment have gained an increasing role in CCA treatment as well. These comprise a wide range of options from tumor ablation procedures such as radiofrequency ablation (RFA), microwave ablation (MWA), computed tomography high-dose rate brachytherapy (CT-HDRBT), and cryoablation to transarterial chemoembolization (TACE), including the option of intra-arterial administration of radioactive spheres (transarterial radioembolization-TARE), and much attention has focused on the potential of individual concepts in recent years. The purpose of this review is to provide an overview of current radiologic interventions for CCA (excluding options for eCCA), to review and appraise the existing literature on the topic, and to provide an outlook on whether such interventions may have a role as treatment for cHCC-CCA in the future.
Published: 2023
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38. Serum CXCL5 Detects Early Hepatocellular Carcinoma and Indicates Tumor Progression.

Author: Laschtowitz A, Lambrecht J, Puengel T, Tacke F, and Mohr R
Subjects: Humans, Liver Cirrhosis pathology, Chemokines, Inflammation, Chemokine CXCL10, Chemokine CXCL5, Carcinoma, Hepatocellular pathology, Liver Neoplasms pathology
Abstract: Chemokines or chemotactic cytokines play a pivotal role in the immune pathogenesis of liver cirrhosis and hepatocellular carcinoma (HCC). Nevertheless, comprehensive cytokine profiling data across different etiologies of liver diseases are lacking. Chemokines might serve as diagnostic and prognostic biomarkers. In our study, we analyzed serum concentrations of 12 inflammation-related chemokines in a cohort of patients ( n = 222) with cirrhosis of different etiologies and/or HCC. We compared 97 patients with cirrhosis and treatment-naïve HCC to the chemokine profile of 125 patients with cirrhosis but confirmed absence of HCC. Nine out of twelve chemokines were significantly elevated in sera of cirrhotic patients with HCC compared to HCC-free cirrhosis controls (CCL2, CCL11, CCL17, CCL20, CXCL1, CXCL5, CXCL9, CXCL10, CXCL11). Among those, CXCL5, CXCL9, CXCL10, and CXCL11 were significantly elevated in patients with early HCC according to the Barcelona Clinic Liver Cancer (BCLC) stages 0/A compared to cirrhotic controls without HCC. In patients with HCC, CXCL5 serum levels were associated with tumor progression, and levels of CCL20 and CXCL8 with macrovascular invasion. Importantly, our study identified CXCL5, CXCL9, and CXCL10 as universal HCC markers, independent from underlying etiology of cirrhosis. In conclusion, regardless of the underlying liver disease, patients with cirrhosis share an HCC-specific chemokine profile. CXCL5 may serve as a diagnostic biomarker in cirrhotic patients for early HCC detection as well as for tumor progression.
Published: 2023
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39. Examining Implicit Biases of Pre-Service Educators Within a Professional Development Context.

Author: Breese AC, Nickerson AB, Lemke M, Mohr R, Heidelburg K, Fredrick S, and Allen K
Abstract: The opportunity gap, or conditions and barriers that impede the academic performance and school experience of minoritized students, may be exacerbated by educators' implicit biases. The aim of this qualitative study was to understand preservice educators' awareness of individual, structural, and systemic racism with regard to implicit bias. Our sample included 154 preservice educators, enrolled in an anti-bullying/harassment/discrimination training, which is required for any New York State (NYS) educator certification. Educators responded to questions about group generalizations, factors contributing to these biases, and how biases may affect their behavior toward students. Our content analysis revealed several themes, most notably that frequent biases existed toward Asian/Asian Americans, Black/African Americans, males, and people from socioeconomically disadvantaged backgrounds. Although participant responses reflect an open-minded approach to discussing bias, many responses reflected no observable desire to change potentially biased interactions with students. Responses with racially held biases aligned with the tenets of critical race theory (CRT), particularly racism as permanent and racism as normalized. Implications for practice, with an emphasis on anti-bias training and professional development, are discussed., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to California Association of School Psychologists 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)
Published: 2023
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40. Autoantibody profiles in patients with immune checkpoint inhibitor-induced neurological immune related adverse events.

Author: Müller-Jensen L, Knauss S, Ginesta Roque L, Schinke C, Maierhof SK, Bartels F, Finke C, Rentzsch K, Ulrich C, Mohr R, Stenzel W, Endres M, Boehmerle W, and Huehnchen P
Subjects: Humans, Immune Checkpoint Inhibitors adverse effects, Autoantibodies, Cohort Studies, Immune System Diseases, Lung Neoplasms
Abstract: Background: Neurological immune-related adverse events (irAE-n) are severe and potentially fatal toxicities of immune checkpoint inhibitors (ICI). To date, the clinical significance of neuronal autoantibodies in irAE-n is poorly understood. Here, we characterize neuronal autoantibody profiles in patients with irAE-n and compare these with ICI-treated cancer patients without irAE-n., Methods: In this cohort study (DRKS00012668), we consecutively collected clinical data and serum samples of 29 cancer patients with irAE-n (n = 2 pre-ICI, n = 29 post-ICI) and 44 cancer control patients without irAE-n (n = 44 pre- and post-ICI). Using indirect immunofluorescence and immunoblot assays, serum samples were tested for a large panel of neuromuscular and brain-reactive autoantibodies., Results: IrAE-n patients and controls received ICI treatment targeting programmed death protein (PD-)1 (61% and 62%), programmed death ligand (PD-L)1 (18% and 33%) or PD-1 and cytotoxic T-lymphocyte-associated protein (CTLA-)4 (21% and 5%). Most common malignancies were melanoma (both 55%) and lung cancer (11% and 14%). IrAE-n affected the peripheral nervous system (59%), the central nervous system (21%), or both (21%). Prevalence of neuromuscular autoantibodies was 63% in irAE-n patients, which was higher compared to ICI-treated cancer patients without irAE-n (7%, p <.0001). Brain-reactive autoantibodies targeting surface (anti-GABA B R, -NMDAR, -myelin), intracellular (anti-GFAP, -Zic4, -septin complex), or unknown antigens were detected in 13 irAE-n patients (45%). In contrast, only 9 of 44 controls (20%) presented brain-reactive autoantibodies before ICI administration. However, seven controls developed de novo brain-reactive autoantibodies after ICI initiation, therefore, prevalence of brain-reactive autoantibodies was comparable between ICI-treated patients with and without irAE-n (p = .36). While there was no clear association between specific brain-reactive autoantibodies and clinical presentation, presence of at least one of six selected neuromuscular autoantibodies (anti-titin, anti-skeletal muscle, anti-heart muscle, anti-LRP4, anti-RyR, anti-AchR) had a sensitivity of 80% (95% CI 0.52-0.96) and a specificity of 88% (95% CI 0.76-0.95) for the diagnosis of myositis, myocarditis, or myasthenia gravis., Conclusion: Neuromuscular autoantibodies may serve as a feasible marker to diagnose and potentially predict life-threatening ICI-induced neuromuscular disease. However, brain-reactive autoantibodies are common in both ICI-treated patients with and without irAE-n, hence, their pathogenic significance remains unclear., Competing Interests: Author KR is employed by the Clinical Immunological Laboratory Prof. Dr. med. Winfried Stöcker. The authors declare that this study received funding from EUROIMMUN AG. The funder had the following involvement in the study: Provision of autoantibody assays for brain reactive autoantibodies. WB and PH have received lecture fees from Bristol-Meyers Squibb WB and NOGGO eV. WB and PH. ME reports grants from Bayer and fees paid to the Charité from Abbot, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, Sanofi, Novartis, Pfizer, all outside the submitted work., (Copyright © 2023 Müller-Jensen, Knauss, Ginesta Roque, Schinke, Maierhof, Bartels, Finke, Rentzsch, Ulrich, Mohr, Stenzel, Endres, Boehmerle and Huehnchen.)
Published: 2023
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41. Single-cell RNA sequencing identifies a population of human liver-type ILC1s.

Author: Krämer B, Nalin AP, Ma F, Eickhoff S, Lutz P, Leonardelli S, Goeser F, Finnemann C, Hack G, Raabe J, ToVinh M, Ahmad S, Hoffmeister C, Kaiser KM, Manekeller S, Branchi V, Bald T, Hölzel M, Hüneburg R, Nischalke HD, Semaan A, Langhans B, Kaczmarek DJ, Benner B, Lordo MR, Kowalski J, Gerhardt A, Timm J, Toma M, Mohr R, Türler A, Charpentier A, van Bremen T, Feldmann G, Sattler A, Kotsch K, Abdallah AT, Strassburg CP, Spengler U, Carson WE 3rd, Mundy-Bosse BL, Pellegrini M, O'Sullivan TE, Freud AG, and Nattermann J
Subjects: Humans, Endothelial Cells, Killer Cells, Natural, Liver, Transcription Factors, Sequence Analysis, RNA, Lymphocytes, Immunity, Innate
Abstract: Group 1 innate lymphoid cells (ILCs) comprise a heterogeneous family of cytotoxic natural killer (NK) cells and ILC1s. We identify a population of "liver-type" ILC1s with transcriptional, phenotypic, and functional features distinct from those of conventional and liver-resident NK cells as well as from other previously described human ILC1 subsets. LT-ILC1s are CD49a + CD94 + CD200R1 + , express the transcription factor T-BET, and do not express the activating receptor NKp80 or the transcription factor EOMES. Similar to NK cells, liver-type ILC1s produce IFN-γ, TNF-α, and GM-CSF; however, liver-type ILC1s also produce IL-2 and lack perforin and granzyme-B. Liver-type ILC1s are expanded in cirrhotic liver tissues, and they can be produced from blood-derived ILC precursors in vitro in the presence of TGF-β1 and liver sinusoidal endothelial cells. Cells with similar signature and function can also be found in tonsil and intestinal tissues. Collectively, our study identifies and classifies a population of human cross-tissue ILC1s., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Published: 2023
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42. [Operating during pregnancy].

Author: Bleiziffer S, Hanke J, Färber G, Martens S, Mohr R, Keuder A, Cleuziou J, and Niethard M
Published: 2023
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43. The Diagnostic Approach towards Combined Hepatocellular-Cholangiocarcinoma-State of the Art and Future Perspectives.

Author: Eschrich J, Kobus Z, Geisel D, Halskov S, Roßner F, Roderburg C, Mohr R, and Tacke F
Abstract: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer which displays clinicopathologic features of both hepatocellular (HCC) and cholangiocellular carcinoma (CCA). The similarity to HCC and CCA makes the diagnostic workup particularly challenging. Alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA 19-9) are blood tumour markers related with HCC and CCA, respectively. They can be used as diagnostic markers in cHCC-CCA as well, albeit with low sensitivity. The imaging features of cHCC-CCA overlap with those of HCC and CCA, dependent on the predominant histopathological component. Using the Liver Imaging and Reporting Data System (LI-RADS), as many as half of cHCC-CCAs may be falsely categorised as HCC. This is especially relevant since the diagnosis of HCC may be made without histopathological confirmation in certain cases. Thus, in instances of diagnostic uncertainty (e.g., simultaneous radiological HCC and CCA features, elevation of CA 19-9 and AFP, HCC imaging features and elevated CA 19-9, and vice versa) multiple image-guided core needle biopsies should be performed and analysed by an experienced pathologist. Recent advances in the molecular characterisation of cHCC-CCA, innovative diagnostic approaches (e.g., liquid biopsies) and methods to analyse multiple data points (e.g., clinical, radiological, laboratory, molecular, histopathological features) in an all-encompassing way (e.g., by using artificial intelligence) might help to address some of the existing diagnostic challenges.
Published: 2023
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44. Atezolizumab Plus Bevacizumab in Patients with Advanced and Progressing Hepatocellular Carcinoma: Retrospective Multicenter Experience.

Author: Sinner F, Pinter M, Scheiner B, Ettrich TJ, Sturm N, Gonzalez-Carmona MA, Waidmann O, Finkelmeier F, Himmelsbach V, De Toni EN, Ben Khaled N, Mohr R, Fründt TW, Kütting F, Bömmel FV, Lieb S, Krug S, Bettinger D, Schultheiß M, Jochheim LS, Best J, Müller C, Keitel V, and Venerito M
Abstract: Atezolizumab plus bevacizumab is the standard of care for first-line systemic therapy for advanced hepatocellular carcinoma (aHCC). Data on the efficacy and safety of atezolizumab plus bevacizumab in patients with aHCC who have received prior systemic therapy are not available. Methods: Patients with aHCC who received atezolizumab plus bevacizumab after at least one systemic treatment between December 2018 and March 2022 were retrospectively identified in 13 centers in Germany and Austria. Patient characteristics, tumor response rates, progression-free survival (PFS), overall survival (OS), and adverse events (AE) were analyzed. Results: A total of 50 patients were identified; 41 (82%) were male. The median age at initiation of treatment with atezolizumab plus bevacizumab was 65 years, 41 (82%) patients had cirrhosis, 30 (73%) Child A, 9 (22%) B, and 2 (5%) C. A total of 34 patients (68%) received atezolizumab plus bevacizumab in the second-line setting and 16 (32%) in later lines. The best radiologic tumor responses were complete remission (2%), partial remission (30%), stable disease (36%), and progressive disease (18%), resulting in an objective response rate of 32% and a disease control rate of 68%. Median OS was 16.0 months (95% confidence interval 5.6-26.4 months), and median PFS was 7.1 months (95% confidence interval 4.4-9.8 months). AE grades 3-4 were observed in seven (14%) and resulted in death in three patients (6%). There were five (10%) bleeding events with a grade ≥ 3, including one (2%) with a fatal outcome. Conclusions: Atezolizumab plus bevacizumab is effective in patients with aHCC who did not have access to this option as first-line therapy. The safety profile was consistent with previous reports.
Published: 2022
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45. Saphenous Vein vs Arterial Graft to the Right System in Left-Sided Arterial Revascularization.

Author: Ben-Gal Y, Gordon A, Teich N, Sela O, Kramer A, Ziv-Baran T, Mohr R, and Pevni D
Subjects: Humans, Saphenous Vein transplantation, Coronary Vessels surgery, Proportional Hazards Models, Treatment Outcome, Vascular Patency, Mammary Arteries transplantation, Gastroepiploic Artery
Abstract: Background: To investigate clinical outcomes of various arterial grafts (AGs) vs saphenous vein grafts (VGs) to the right coronary system in patients who received left-sided bilateral internal thoracic artery revascularization., Methods: We compared short- and long-term outcomes of all the patients operated in our center during 1996-2011, who received left-sided bilateral internal thoracic artery (left anterior descending and left circumflex) grafting and either a VG or an AG to the right coronary system., Results: Of 1691 patients, 983 received a VG and 708 received an AG to the right coronary system: 387 gastroepiploic arteries and 321 internal thoracic artery grafts. The median follow-up was 15.7 ± 0.32 years. For the VG and AG groups, early mortality (1.6% for VG and 1.3% for AG, P = .55) and other early adverse outcomes did not differ. Long-term (up to 20 years) survival was similar (34.1% ± 3.4% for VG vs 36.0% ±2% for AG, P = .86). In multivariable analysis, VG to the right coronary artery was not found to be a predictor of inferior survival (hazard ratio: 0.99, 95% confidence interval 0.836-1.194, P = .99). Comparing 2 propensity-matched groups of 349 pairs with a VG or an AG, and accounting for the severity of the right coronary lesion, did not demonstrate differences in early outcome or late survival between the groups., Conclusions: Early outcomes and long-term survival were comparable among patients who received left-sided bilateral internal thoracic artery revascularization, between various graft types to the right coronary system., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)
Published: 2022
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46. Characteristics of immune checkpoint inhibitor-induced encephalitis and comparison with HSV-1 and anti-LGI1 encephalitis: A retrospective multicentre cohort study.

Author: Müller-Jensen L, Zierold S, Versluis JM, Boehmerle W, Huehnchen P, Endres M, Mohr R, Compter A, Blank CU, Hagenacker T, Meier F, Reinhardt L, Gesierich A, Salzmann M, Hassel JC, Ugurel S, Zimmer L, Banks P, Spain L, Soon JA, Enokida T, Tahara M, Kähler KC, Seggewiss-Bernhardt R, Harvey C, Long GV, Schöberl F, von Baumgarten L, Hundsberger T, Schlaak M, French LE, Knauss S, and Heinzerling LM
Subjects: Autoantibodies, Cohort Studies, Humans, Immune Checkpoint Inhibitors adverse effects, Intracellular Signaling Peptides and Proteins, Leucine, Retrospective Studies, Encephalitis chemically induced, Glioma, Herpesvirus 1, Human
Abstract: Aim: Immune checkpoint inhibitor-induced encephalitis (ICI-iE) is a rare but life-threatening toxicity of immune checkpoint inhibitor treatment. We aim to identify the characteristics of ICI-iE and describe factors that discriminate it from herpes simplex virus (HSV)-1 encephalitis and anti-leucine-rich glioma-inactivated 1 (anti-LGI1) encephalitis, as two alternative entities of encephalitis., Methods: In this retrospective multicentre cohort study, we collected patients with ICI-iE reported to the Side Effect Registry Immuno-Oncology from January 2015 to September 2021 and compared their clinical features and outcome with 46 consecutive patients with HSV-1 or anti-LGI1 encephalitis who were treated at a German neurological referral centre., Results: Thirty cases of ICI-iE, 25 cases of HSV-1 encephalitis and 21 cases of anti-LGI1 encephalitis were included. Clinical presentation of ICI-iE was highly variable and resembled that of HSV-1 encephalitis, while impairment of consciousness (66% vs. 5%, p = .007), confusion (83% vs. 43%; p = .02), disorientation (83% vs. 29%; p = .007) and aphasia (43% vs. 0%; p = .007) were more common in ICI-iE than in anti-LGI1 encephalitis. Antineuronal antibodies (17/18, 94%) and MRI (18/30, 60%) were mostly negative in ICI-iE, but cerebrospinal fluid (CSF) showed pleocytosis and/or elevated protein levels in almost all patients (28/29, 97%). Three patients (10%) died of ICI-iE. Early immunosuppressive treatment was associated with better outcome (r = 0.43)., Conclusions: ICI-iE is a heterogeneous entity without specific clinical features. CSF analysis has the highest diagnostic value, as it reveals inflammatory changes in most patients and enables the exclusion of infection. Early treatment of ICI-iE is essential to prevent sequelae and death., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: LMJ, JMV, WB, PH, RM, AC, TH, FM, LR, PB, JAS, TE, MT, CH, LvB, THu, declare no conflicts of interest. SZ declares speaker's fees or travel grants from Bristol-Myers Squibb (BMS), Sun Pharma and Merck Sharp & Dohme (MSD). ME received funding from DFG under Germany's Excellence Strategy – EXC-2049 – 390688087, BMBF, DZNE, DZHK, EU, Corona Foundation, and Foundation Leducq. ME reports grants from Bayer and fees paid to the Charité from AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, Amgen, GSK, Sanofi, Covidien, Novartis, Pfizer, all outside the submitted work. CUB received compensation (all paid to the institute except TRV) for advisory roles for BMS, MSD, Roche, Novartis, GlaxoSmithKline, AstraZeneca, Pfizer, Lilly, GenMab, Pierre Fabre Pharmaceuticals, Third Rock Ventures, received research funding (all paid to the institute) from BMS, Novartis, NanoString, and declares stockownership in Immagene BV, where he is co-founder. AG received speaker's honoraria from Allmiral, BMS, MSD and Roche; AG has intermittent advisory board relationships with Amgen, BMS, Novartis, MSD, Pierre Fabre Pharmaceuticals, Pfizer, Roche and Sanofi Genzyme; travel and congress fee support from BMS, MSD, Novartis, Pierre Fabre Pharmaceuticals and Roche. Clinical studies: Amgen, Array, BMS, GSK, Novartis, Merck, MSD, Pfizer, and Roche. MS received speaker's honoraria and travel grants from Abbvie, BMS, Merck, MSD, Novartis, Pfizer, and Sanofi. JCH has served as a consultant for GSK, MSD, Pierre Fabre Pharmaceuticals, Sunpharma (personal) and BMS, Immunocore, Nektar, Novartis, Philogen (institution); received speaker's honoraria from Almirall, Amgen, BMS, GSK, MSD, Novartis, Pfizer, Pierre Fabre Pharmaceuticals, Roche, Sanofi (personal); a scientific grant from BMS and Sunpharma (institution) and clinical trial honoraria for BioNTech, BMS, Genentech, Immunocore, Iovance, MSD, Novartis, Philogen, Pierre Fabre Pharmaceuticals, Regeneron, Roche, Sanofi, 4SC (institution). SU declares research support from Bristol Myers Squibb and Merck Serono; speakers and advisory board honoraria from Bristol Myers Squibb, MSD, Merck Serono, Novartis and Roche, and travel support from Bristol Myers Squibb, MSD, and Pierre Fabre Pharmaceuticals. LZ served as consultant and/or has received honoraria from BMS, MSD, Novartis, Pierre-Fabre Pharmaceuticals, Sunpharma and Sanofi; Research funding to institution: Novartis; travel support from MSD, BMS, Amgen, Pierre-Fabre Pharmaceuticals, Sunpharma, Sanofi and Novartis, outside the submitted work. LS declares advisory and speaker honoraria from Bristol Myers Squibb. KCK has served as consultant or/and has received honoraria from Amgen, Roche, Bristol Myers Squibb, Merck Sharp and Dohme, Pierre Fabre Pharmaceuticals, and Novartis, and received travel support from Amgen, Merck Sharp and Dohme, Bristol Myers Squibb, Amgen, Pierre Fabre Pharmaceuticals, Medac and Novartis. RSB has served as consultant for and/or received honoraria from Amgen, AstraZeneca, BMS, Celgene, Jansen-Cilag, MSD, Merck Seono, Novartis, Pfizer, and Roche. GVL is consultant advisor for Agenus, Amgen, Array Biopharma, Boehringer Ingelheim, BMS, Evaxion, Hexal AG (Sandoz Company), Highlight Therapeutics S.L., Innovent Biologics USA, MSD, Novartis Pharma AG, OncoSec, PHMR Limited, Pierre Fabre Pharmaceuticals, Provectus, Qbiotics, Regeneron. FS has received an honorarium from Gilead for an advisory board meeting. MS received speaker's honoraria and participated in advisory boards of BMS, Novartis, MSD, Roche, Pierre Fabre Pharmaceuticals, Kyowa Kirin, Immunocore, Recordati and Sanofi-Genzyme. MS received travel accommodation and expenses by Novartis, Pierre Fabre Pharmaceuticals, and Sun Pharma. LEF has served as consultant for Galderma, Janssen, Leo Pharma, Eli Lilly, Almirall, Union Therapeutics, Regeneron, Novartis, Amgen, Abbvie, UCB, Biotest, and InflaRx. SK received compensation for advising roles for Biogen. LH has served as consultant for Amgen, BMS, Biome-dx, EMA, Immunocore, Kyowa Kirin, MSD, Novartis, Pierre Fabre Pharmaceuticals, Roche, and Sanofi., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Published: 2022
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47. Dietary omega-6/omega-3 ratio is not associated with gut microbiota composition and disease severity in patients with nonalcoholic fatty liver disease.

Author: Heinzer K, Lang S, Farowski F, Wisplinghoff H, Vehreschild MJGT, Martin A, Nowag A, Kretzschmar A, Scholz CJ, Roderburg C, Mohr R, Tacke F, Kasper P, Goeser T, Steffen HM, and Demir M
Subjects: Humans, RNA, Ribosomal, 16S genetics, Cross-Sectional Studies, Bacteria genetics, Severity of Illness Index, Non-alcoholic Fatty Liver Disease etiology, Gastrointestinal Microbiome physiology, Fatty Acids, Omega-3
Abstract: In this cross-sectional study, we hypothesized that a high dietary ratio of omega-6 (n-6) to omega-3 (n-3) fatty acids could be associated with an altered gut bacterial composition and with the disease severity in patients with nonalcoholic fatty liver disease (NAFLD). A total of 101 NAFLD patients were included in the study, of which 63 underwent a liver biopsy. All 101 patients completed a 14-day food and activity record. Ebispro 2016 professional software was used to calculate individual macronutrients and micronutrients consumed. Patients were grouped into 3 quantiles (Q) according to a low (Q1: <6.1, n = 34), moderate (Q2: 6.1-7.8, n = 33), or high (Q3: >7.8, n = 34) dietary n-6/n-3 ratio. Stool samples were analyzed using 16S rRNA gene sequencing. Spearman correlation coefficients and principal coordinate analysis were used to detect differences in the bacterial composition of the gut microbiota. The median dietary n-6/n-3 ratio of all patients was 6.7 (range, 3.1-14.9). No significant associations between the dietary n-6/n-3 ratio and the gut microbiota composition or disease severity were observed. However, the abundance of specific bacteria such as Catenibacterium or Lactobacillus ruminis were found to be positively correlated and the abundance of Clostridium were negatively correlated with dietary n-6 fatty acid intake. The results indicate that a high dietary n-6/n-3 ratio is probably not a highly relevant factor in the pathogenesis of human NAFLD. Further studies are needed to clarify the importance of interactions between gut bacterial taxa and n-6 fatty acids in the pathophysiology of NAFLD., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)
Published: 2022
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48. Inflammatory Cytokines Associated with Diagnosis, Tumor Grade and Prognosis in Patients with Neuroendocrine Tumors.

Author: Geisler L, Hellberg T, Lambrecht J, Jann H, Knorr J, Eschrich J, Loosen SH, Wree A, Hammerich L, Krieg A, Luedde T, Tacke F, Roderburg C, and Mohr R
Abstract: Background and aims: Inflammatory cytokines represent diagnostic and prognostic biomarkers in manifold cancers. Recent data suggest a pivotal role of these cytokines in different biological processes involved in the development of neuroendocrine tumors (NETs). However, their role as biomarkers in NETs is only poorly understood. Methods: We analyzed serum concentrations of 13 inflammation-related cytokines at different time points in 43 patients with well-differentiated gastroenteropancreatic NETs (G1/G2) treated at Charité Berlin and compared them to 40 healthy controls. The results were correlated with clinical records. Results: Serum concentrations (Median (Interquartile Range (IQR)) in pg/mL) of IL-1β (124 (82) vs. 68 (61) pg/mL; p = 0.0003), IL-6 (111(122) vs. 88 (32) pg/mL; p = 0.0086), IL-8 (1058 (768) vs. 210 (90) pg/mL; p < 0.0001), IL-18 (2936 (1723) vs. 1590 (704) pg/mL; p < 0.0001), and TNF (271 (260) vs. 42 (25) pg/mL; p < 0.0001) were significantly elevated in NET patients, whereas IL-10 (43 (44) vs. 105 (48) pg/mL; p < 0.0001) showed lower concentrations in NETs when compared to controls. Cytokine levels significantly correlated with tumor grade (IL-6; p = 0.0070), prevalence of distant metastasis (IL-18; p = 0.0313), and disease progression over time (IL-10; p = 0.0033) but not tumor location. Chromogranin A (CgA) and the NETest are currently used to monitor treatment response. A more accurate prediction could possibly be achieved by employing a subset of cytokines. Our data clearly warrants further functional investigation into the role of the immune response and cytokine release in NETs. Conclusion: A biologically plausible panel of cytokines might be added to the diagnostic and prognostic tools currently employed in patients with NETs. Combining different markers into a score would elevate diagnostic accuracy compared to single markers.
Published: 2022
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49. Dataset of a retrospective multicenter cohort study on characteristics of immune checkpoint inhibitor-induced encephalitis and comparison with HSV-1 and anti-LGI1 encephalitis.

Author: Müller-Jensen L, Zierold S, Versluis JM, Boehmerle W, Huehnchen P, Endres M, Mohr R, Compter A, Blank CU, Hagenacker T, Meier F, Reinhardt L, Gesierich A, Salzmann M, Hassel JC, Ugurel S, Zimmer L, Banks P, Spain L, Soon JA, Enokida T, Tahara M, Kähler KC, Seggewiss-Bernhardt R, Harvey C, Long GV, Schöberl F, von Baumgarten L, Hundsberger T, Schlaak M, French LE, Knauss S, and Heinzerling LM
Abstract: Over the past decade, cancer immunotherapy with immune checkpoint inhibitors (ICIs) has significantly improved the outcome of many malignancies. However, with the broad use of ICIs, neurological immune related adverse events (irAE) are increasingly recognized. ICI-induced encephalitis (ICI-iE) is a particularly severe irAE, often leading to treatment termination, long-term sequalae or death. Despite its high morbidity and mortality, data on clinical features and diagnostic criteria are limited. We aimed to define clinical, radiologic and laboratory characteristics of ICI-iE and identify factors that discriminate it from anti-leucine-rich glioma-inactivated (anti-LGI)-1 encephalitis and herpes simplex virus (HSV)-1 encephalitis - two alternative causes of encephalitis - to increase the awareness of ICI-iE and improve its diagnosis and management. To that end, we retrospectively collected 30 cases of ICI-iE that were reported to the Side Effect Registry Immuno-Oncology (SERIO) and 46 cases of anti-LGI1 encephalitis or herpes simplex virus (HSV)-1 encephalitis that presented to a large German neurological referral center (Charité Universitätsmedizin Berlin) between January 2015 and September 2021. Signs and symptoms, imaging and electroencephalogram features, laboratory findings and outcome measures were assessed using standardized case report forms as well as patients' medical records and compared between the groups. The data reported here represents the largest primary cohort of patients with ICI-iE to date and the first comparison with other types of encephalitis. As all three disorders - ICI-iE, HSV-1 encephalitis and anti-LGI1 encephalitis - are rare neurological entities, this dataset can be used as a reference in future clinical studies on ICI-induced neurotoxicity, neurological autoimmune disorders, and central nervous system infections., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. X The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: LMJ, JMV, WB, PH, RM, AC, TH, FM, LR, PB, JAS, TE, MT, CH, LvB, THu, declare no conflicts of interest. SZ declares speaker's fees or travel grants from Bristol-Myers Squibb (BMS), Sun Pharma and Merck Sharp & Dohme (MSD). ME received funding from DFG under Germany´s Excellence Strategy – EXC-2049 – 390688087, BMBF, DZNE, DZHK, EU, Corona Foundation, and Fondation Leducq. ME reports grants from Bayer and fees paid to the Charité from AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, Amgen, GSK, Sanofi, Covidien, Novartis, Pfizer, all outside the submitted work. CUB received compensation (all paid to the institute except TRV) for advisory roles for BMS, MSD, Roche, Novartis, GlaxoSmithKline, AstraZeneca, Pfizer, Lilly, GenMab, Pierre Fabre, Third Rock Ventures, received research funding (all paid to the institute) from BMS, Novartis, NanoString, and declares stockownership in Immagene BV, where he is co-founder. AG received speaker´s honoraria from Allmiral, BMS, MSD and Roche; AG has intermittent advisory board relationships with Amgen, BMS, Novartis, MSD, Pierre Fabre Pharmaceuticals, Pfizer, Roche and Sanofi Genzyme; travel and congress fee support from BMS, MSD, Novartis, Pierre Fabre Pharmaceuticals and Roche. Clinical studies: Amgen, Array, BMS, GSK, Novartis, Merck, MSD, Pfizer, and Roche. MS received speaker's honoraria and travel grants from Abbvie, BMS, Merck, MSD, Novartis, Pfizer, and Sanofi. JCH has served as a consultant for GSK, MSD, Pierre Fabre, Sun Pharma (personal) and BMS, Immunocore, Nektar, Novartis, Philogen (institution); received speaker's honoraria from Almirall, Amgen, BMS, GSK, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi (personal); a scientific grant from BMS and Sun Pharma (institution) and clinical trial honoraria for BioNTech, BMS, Genentech, Immunocore, Iovance, MSD, Novartis, Philogen, Pierre Fabre, Regeneron, Roche, Sanofi, 4SC (institution). SU declares research support from BMS and Merck Serono; speakers and advisory board honoraria from BMS, MSD, Merck Serono, Novartis and Roche, and travel support from BMS, MSD, and Pierre Fabre Pharmaceuticals. LZ served as consultant and/or has received honoraria from BMS, MSD, Novartis, Pierre Fabre Pharmaceuticals, Sun Pharma and Sanofi; Research funding to institution: Novartis; travel support from MSD, BMS, Amgen, Pierre-Fabre, Sun Pharma, Sanofi and Novartis, outside the submitted work. LS declares advisory and speaker honoraria from BMS. KCK has served as consultant or/and has received honoraria from Amgen, Roche, BMS, MSD, Pierre Fabre Pharmaceuticals, and Novartis, and received travel support from Amgen, BMS, MSD, Amgen, Pierre Fabre Pharmaceuticals, Medac and Novartis. RSB has served as consultant for and/or received honoraria from Amgen, AstraZeneca, BMS, Celgene, Jansen-Cilag, MSD, Merck Seono, Novartis, Pfizer, and Roche. GVL is consultant advisor for Agenus, Amgen, Array Biopharma, Boehringer Ingelheim, BMS, Evaxion, Hexal AG (Sandoz Company), Highlight Therapeutics S.L., Innovent Biologics USA, MSD, Novartis Pharma AG, OncoSec, PHMR Limited, Pierre Fabre Pharmaceuticals, Provectus, Qbiotics, Regeneron. FS has received an honorarium from Gilead for an advisory board meeting. MS received speaker's honoraria and participated in advisory boards of BMS, Novartis, MSD, Roche, Pierre Fabre Pharmaceuticals, Kyowa Kirin, Immunocore, Recordati and Sanofi-Genzyme. MS received travel accommodation and expenses by Novartis, Pierre Fabre Pharmaceuticals, and Sun Pharma. LEF has served as consultant for Galderma, Janssen, Leo Pharma, Eli Lilly, Almirall, Union Therapeutics, Regeneron, Novartis, Amgen, Abbvie, UCB, Biotest, and InflaRx. SK received compensation for advising roles for Biogen. LH has served as consultant for Amgen, BMS, Biome-dx, EMA, Immunocore, Kyowa Kirin, MSD, Novartis, Pierre Fabre Pharmaceuticals, Roche, and Sanofi., (© 2022 The Authors.)
Published: 2022
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50. Shear wave elastography-based liver fibrosis assessment in patients with chronic hepatitis E displays elevated liver stiffness regardless of previous antiviral therapy.

Author: Schulz M, Choi M, Bachmann F, Koch N, Holtmann TM, Mohr R, Tacke F, and Wree A
Abstract: Background: Hepatitis E virus (HEV) infection especially in immunocompromised individuals can lead to chronic hepatitis. Aggressive courses of chronic hepatitis E leading to liver cirrhosis in a short period of time have been described, but evidence on the degree of liver involvement in chronic hepatitis E is rare. We therefore aimed to quantify liver fibrosis in patients with chronic active hepatitis E compared to patients with sustained virological response after ribavirin (RBV) treatment using 2D-shear wave elastography (2D-SWE) to measure liver stiffness., Methods: Patients with chronic hepatitis E underwent 2D-SWE, B-mode and Doppler ultrasound and laboratory testing in order to assess severity of liver involvement., Results: In this cross-sectional study, we included 14 patients of whom 8 had ongoing chronic hepatitis E and 6 patients had been successfully treated for chronic hepatitis E. The most frequent cause for immunosuppression was prior kidney transplantation (n=12), one patient was a multivisceral transplant recipient, one had been treated for lymphoma. Five patients cleared HEV after RBV therapy, one patient reached viral clearance after reduction of his immunosuppressive medication. Using 2D-SWE measurement, 71.4% displayed increased stiffness indicative of liver fibrosis: 57.1% classified as significant fibrosis and 14.3% as severe fibrosis. Liver stiffness did not differ between patients with active chronic hepatitis E and in patients who had cleared HEV (1.59 and 1.54 m/s respectively). Compared with a control group of kidney transplant recipients without hepatitis E (1.44 m/s), the patients with a history of hepatitis E displayed a significantly higher liver stiffness (P=0.04)., Conclusions: In our cohort of chronic hepatitis E patients, elevated liver stiffness indicating liver fibrosis was common and significantly higher than in controls. This is consistent with prior sparse reports of the presence of liver fibrosis or cirrhosis in chronic hepatitis E and emphasizes the need for HEV testing, therapy and research on new therapeutic options. As elevated liver stiffness was also present in patients after HEV treatment, continuous liver surveillance including elastography and ultrasound should be considered., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-21-1178/coif). FT reports that the laboratory of FT has received funding from Allergan, BMS, Inventiva and Gilead. FT has received honoraria or consulting fees from Allergan, Alnylam, Bayer, Gilead, BMS, Boehringer, Intercept, Ionis, Inventiva, Merz, Pfizer, NGM, CSL Behring, Novo Nordisk, Novartis, Falk. The consulting activities are unrelated to the current study. The other authors have no conflicts of interest to declare., (2022 Quantitative Imaging in Medicine and Surgery. All rights reserved.)
Published: 2022
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