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3. Parameter Space and Potential for Biomarker Development in 25 Years of fMRI Drug Cue Reactivity: A Systematic Review.

Author

Sangchooli, Arshiya, Zare-Bidoky, Mehran, Fathi Jouzdani, Ali, Schacht, Joseph, Bjork, James, Claus, Eric, Prisciandaro, James, Wilson, Stephen, Wüstenberg, Torsten, Potvin, Stéphane, Ahmadi, Pooria, Bach, Patrick, Baldacchino, Alex, Beck, Anne, Brady, Kathleen, Brewer, Judson, Childress, Anna, Courtney, Kelly, Ebrahimi, Mohsen, Filbey, Francesca, Garavan, Hugh, Ghahremani, Dara, Goldstein, Rita, Goudriaan, Anneke, Grodin, Erica, Hanlon, Colleen, Haugg, Amelie, Heilig, Markus, Heinz, Andreas, Holczer, Adrienn, Van Holst, Ruth, Joseph, Jane, Juliano, Anthony, Kaufman, Marc, Kiefer, Falk, Khojasteh Zonoozi, Arash, Kuplicki, Rayus, Leyton, Marco, London, Edythe, Mackey, Scott, McClernon, F, Mellick, William, Morley, Kirsten, Noori, Hamid, Oghabian, Mohammad, Oliver, Jason, Owens, Max, Paulus, Martin, Perini, Irene, Rafei, Parnian, Ray, Lara, Sinha, Rajita, Smolka, Michael, Soleimani, Ghazaleh, Spanagel, Rainer, Steele, Vaughn, Tapert, Susan, Vollstädt-Klein, Sabine, Wetherill, Reagan, Witkiewitz, Katie, Yuan, Kai, Zhang, Xiaochu, Verdejo-Garcia, Antonio, Potenza, Marc, Janes, Amy, Kober, Hedy, Zilverstand, Anna, and Ekhtiari, Hamed

Abstract

IMPORTANCE: In the last 25 years, functional magnetic resonance imaging drug cue reactivity (FDCR) studies have characterized some core aspects in the neurobiology of drug addiction. However, no FDCR-derived biomarkers have been approved for treatment development or clinical adoption. Traversing this translational gap requires a systematic assessment of the FDCR literature evidence, its heterogeneity, and an evaluation of possible clinical uses of FDCR-derived biomarkers. OBJECTIVE: To summarize the state of the field of FDCR, assess their potential for biomarker development, and outline a clear process for biomarker qualification to guide future research and validation efforts. EVIDENCE REVIEW: The PubMed and Medline databases were searched for every original FDCR investigation published from database inception until December 2022. Collected data covered study design, participant characteristics, FDCR task design, and whether each study provided evidence that might potentially help develop susceptibility, diagnostic, response, prognostic, predictive, or severity biomarkers for 1 or more addictive disorders. FINDINGS: There were 415 FDCR studies published between 1998 and 2022. Most focused on nicotine (122 [29.6%]), alcohol (120 [29.2%]), or cocaine (46 [11.1%]), and most used visual cues (354 [85.3%]). Together, these studies recruited 19 311 participants, including 13 812 individuals with past or current substance use disorders. Most studies could potentially support biomarker development, including diagnostic (143 [32.7%]), treatment response (141 [32.3%]), severity (84 [19.2%]), prognostic (30 [6.9%]), predictive (25 [5.7%]), monitoring (12 [2.7%]), and susceptibility (2 [0.5%]) biomarkers. A total of 155 interventional studies used FDCR, mostly to investigate pharmacological (67 [43.2%]) or cognitive/behavioral (51 [32.9%]) interventions; 141 studies used FDCR as a response measure, of which 125 (88.7%) reported significant interventional FDCR alterations; and 25 studies used FDCR as an intervention outcome predictor, with 24 (96%) finding significant associations between FDCR markers and treatment outcomes. CONCLUSIONS AND RELEVANCE: Based on this systematic review and the proposed biomarker development framework, there is a pathway for the development and regulatory qualification of FDCR-based biomarkers of addiction and recovery. Further validation could support the use of FDCR-derived measures, potentially accelerating treatment development and improving diagnostic, prognostic, and predictive clinical judgments.

Published
2024

5. Fecal cytolysin does not predict disease severity in acutely decompensated cirrhosis and acute-on-chronic liver failure

Author

Hartmann, Phillipp, Lang, Sonja, Schierwagen, Robert, Klein, Sabine, Praktiknjo, Michael, Trebicka, Jonel, and Schnabl, Bernd

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Infectious Diseases, Digestive Diseases, Chronic Liver Disease and Cirrhosis, Substance Misuse, Hepatitis, Alcoholism, Alcohol Use and Health, Liver Disease, 4.1 Discovery and preclinical testing of markers and technologies, Oral and gastrointestinal, Good Health and Well Being, Humans, Acute-On-Chronic Liver Failure, End Stage Liver Disease, Severity of Illness Index, Prognosis, Liver Cirrhosis, Cytotoxins, Liver disease, Acute decompensation, Acute -on -chronic liver failure, Microbiome, Model for end -stage liver disease, Acute-on-chronic liver failure, Model for end-stage liver disease, Immunology, Oncology and Carcinogenesis, Gastroenterology & Hepatology, Clinical sciences, Oncology and carcinogenesis
Abstract

BackgroundCirrhosis with acute decompensation (AD) and acute-on-chronic liver failure (ACLF) are characterized by high morbidity and mortality. Cytolysin, a toxin from Enterococcus faecalis (E. faecalis), is associated with mortality in alcohol-associated hepatitis (AH). It is unclear whether cytolysin also contributes to disease severity in AD and ACLF.MethodsWe studied the role of fecal cytolysin in 78 cirrhotic patients with AD/ACLF. Bacterial DNA from fecal samples was extracted and real-time quantitative polymerase chain reaction (PCR) was performed. The association between fecal cytolysin and liver disease severity in cirrhosis with AD or ACLF was analyzed.ResultsFecal cytolysin and E. faecalis abundance did not predict chronic liver failure (CLIF-C) AD and ACLF scores. Presence of fecal cytolysin was not associated with other liver disease markers, including Fibrosis-4 (FIB-4) index, 'Age, serum Bilirubin, INR, and serum Creatinine (ABIC)' score, Child-Pugh score, model for end-stage liver disease (MELD) nor MELD-Na scores in AD or ACLF patients.ConclusionsFecal cytolysin does not predict disease severity in AD and ACLF patients. The predictive value of fecal cytolysin positivity for mortality appears to be restricted to AH.

Published
2023

12. A methodological checklist for fMRI drug cue reactivity studies: development and expert consensus

Author

Ekhtiari, Hamed, Zare-Bidoky, Mehran, Sangchooli, Arshiya, Janes, Amy C, Kaufman, Marc J, Oliver, Jason A, Prisciandaro, James J, Wüstenberg, Torsten, Anton, Raymond F, Bach, Patrick, Baldacchino, Alex, Beck, Anne, Bjork, James M, Brewer, Judson, Childress, Anna Rose, Claus, Eric D, Courtney, Kelly E, Ebrahimi, Mohsen, Filbey, Francesca M, Ghahremani, Dara G, Azbari, Peyman Ghobadi, Goldstein, Rita Z, Goudriaan, Anna E, Grodin, Erica N, Hamilton, J Paul, Hanlon, Colleen A, Hassani-Abharian, Peyman, Heinz, Andreas, Joseph, Jane E, Kiefer, Falk, Zonoozi, Arash Khojasteh, Kober, Hedy, Kuplicki, Rayus, Li, Qiang, London, Edythe D, McClernon, Joseph, Noori, Hamid R, Owens, Max M, Paulus, Martin P, Perini, Irene, Potenza, Marc, Potvin, Stéphane, Ray, Lara, Schacht, Joseph P, Seo, Dongju, Sinha, Rajita, Smolka, Michael N, Spanagel, Rainer, Steele, Vaughn R, Stein, Elliot A, Steins-Loeber, Sabine, Tapert, Susan F, Verdejo-Garcia, Antonio, Vollstädt-Klein, Sabine, Wetherill, Reagan R, Wilson, Stephen J, Witkiewitz, Katie, Yuan, Kai, Zhang, Xiaochu, and Zilverstand, Anna

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Psychology, Substance Misuse, Neurosciences, Behavioral and Social Science, Basic Behavioral and Social Science, Drug Abuse (NIDA only), Brain Disorders, 8.4 Research design and methodologies (health services), Generic health relevance, Good Health and Well Being, Checklist, Cues, Delphi Technique, Humans, Magnetic Resonance Imaging, Reproducibility of Results, Chemical Sciences, Biological Sciences, Medical and Health Sciences, Bioinformatics
Abstract

Cue reactivity is one of the most frequently used paradigms in functional magnetic resonance imaging (fMRI) studies of substance use disorders (SUDs). Although there have been promising results elucidating the neurocognitive mechanisms of SUDs and SUD treatments, the interpretability and reproducibility of these studies is limited by incomplete reporting of participants' characteristics, task design, craving assessment, scanning preparation and analysis decisions in fMRI drug cue reactivity (FDCR) experiments. This hampers clinical translation, not least because systematic review and meta-analysis of published work are difficult. This consensus paper and Delphi study aims to outline the important methodological aspects of FDCR research, present structured recommendations for more comprehensive methods reporting and review the FDCR literature to assess the reporting of items that are deemed important. Forty-five FDCR scientists from around the world participated in this study. First, an initial checklist of items deemed important in FDCR studies was developed by several members of the Enhanced NeuroImaging Genetics through Meta-Analyses (ENIGMA) Addiction working group on the basis of a systematic review. Using a modified Delphi consensus method, all experts were asked to comment on, revise or add items to the initial checklist, and then to rate the importance of each item in subsequent rounds. The reporting status of the items in the final checklist was investigated in 108 recently published FDCR studies identified through a systematic review. By the final round, 38 items reached the consensus threshold and were classified under seven major categories: 'Participants' Characteristics', 'General fMRI Information', 'General Task Information', 'Cue Information', 'Craving Assessment Inside Scanner', 'Craving Assessment Outside Scanner' and 'Pre- and Post-Scanning Considerations'. The review of the 108 FDCR papers revealed significant gaps in the reporting of the items considered important by the experts. For instance, whereas items in the 'General fMRI Information' category were reported in 90.5% of the reviewed papers, items in the 'Pre- and Post-Scanning Considerations' category were reported by only 44.7% of reviewed FDCR studies. Considering the notable and sometimes unexpected gaps in the reporting of items deemed to be important by experts in any FDCR study, the protocols could benefit from the adoption of reporting standards. This checklist, a living document to be updated as the field and its methods advance, can help improve experimental design, reporting and the widespread understanding of the FDCR protocols. This checklist can also provide a sample for developing consensus statements for protocols in other areas of task-based fMRI.

Published
2022

17. Interferon-induced IL-10 drives systemic T-cell dysfunction during chronic liver injury

Author

Hackstein, Carl-Philipp, Spitzer, Jasper, Symeonidis, Konstantinos, Horvatic, Helena, Bedke, Tanja, Steglich, Babett, Klein, Sabine, Assmus, Lisa M., Odainic, Alexandru, Szlapa, Jennifer, Kessler, Nina, Beyer, Marc, Schmithausen, Ricarda, Latz, Eicke, Flavell, Richard A., Garbi, Natalio, Kurts, Christian, Kümmerer, Beate M., Trebicka, Jonel, Roers, Axel, Huber, Samuel, Schmidt, Susanne V., Knolle, Percy A., and Abdullah, Zeinab

Published
2023
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20. Neprilysin-dependent neuropeptide Y cleavage in the liver promotes fibrosis by blocking NPY-receptor 1

Author

Ortiz, Cristina, Klein, Sabine, Reul, Winfried H., Magdaleno, Fernando, Gröschl, Stefanie, Dietrich, Peter, Schierwagen, Robert, Uschner, Frank E., Torres, Sandra, Hieber, Christoph, Meier, Caroline, Kraus, Nico, Tyc, Olaf, Brol, Maximilian, Zeuzem, Stefan, Welsch, Christoph, Poglitsch, Marco, Hellerbrand, Claus, Alfonso-Prieto, Mercedes, Mira, Fabio, Keller, Ulrich auf dem, Tetzner, Anja, Moore, Andrew, Walther, Thomas, and Trebicka, Jonel

Published
2023
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25. Subjective experiences of the addictive potential of E-cigarettes: results from focus group discussions.

Author

Andreas, Marike, Grundinger, Nadja, Wolber, Nadine, Szafran, Daria, Mons, Ute, Vollstädt-Klein, Sabine, Lohner, Valerie, Hughes, Tom, and Schneider, Sven

Subjects
COMPULSIVE behavior, FOCUS groups, QUALITATIVE research, ELECTRONIC cigarettes, INTERVIEWING, SMOKING, BEHAVIOR, DESCRIPTIVE statistics, THEMATIC analysis, DESIRE, RESEARCH methodology
Abstract

Background: Electronic cigarettes (e-cigarettes) have specific properties, such as their taste, vapor, or technicality, which might facilitate experiences of addiction. In this study, we aimed to investigate the subjective experience of the addictive potential of e-cigarettes using qualitative methodology. Method: We conducted semi-structured focus groups with adult e-cigarette users to discuss subjective experiences of addiction. Informed by Braun and Clarke's approach to thematic analysis, we conducted a deductive-inductive analysis in MAXQDA. First, deductive codes were based on the 10 domains of e-cigarette addiction previously identified by Bold and colleagues. Second, we inductively coded those e-cigarette properties that were identified by users to have addictive potential. Results: We conducted five focus group discussions with a total of 14 e-cigarette users (8 male, 6 female). Subjective experiences of e-cigarette addiction discussed by focus group participants accorded with domains of e-cigarette addiction as defined by Bold and colleagues. For example, users reported automatic use, craving, or sensory dependence. The only domains not reported were preference over competing rewards and impaired control. Second, we inductively identified three central properties of the addictive potential of e-cigarettes: unlimited usability, unobtrusiveness, and pleasant taste. Conclusion: Our findings were summarized in the Model of the Addictive Potential of E-cigarettes (MAPE). Understanding which e-cigarette properties lead to subjective experiences of addiction can inform cessation programs for those who want to quit as well as the refinement of measures to assess e-cigarette addiction. [ABSTRACT FROM AUTHOR]

Published
2024
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26. Decompensated MASH-Cirrhosis Model by Acute and Toxic Effects of Phenobarbital.

Author

Kraus, Nico, Uschner, Frank Erhard, Moeslein, Magnus, Schierwagen, Robert, Gu, Wenyi, Brol, Maximilian Joseph, Fürst, Eike, Grünewald, Inga, Lotersztajn, Sophie, Rautou, Pierre-Emmanuel, Duran-Güell, Marta, Flores Costa, Roger, Clària, Joan, Trebicka, Jonel, and Klein, Sabine

Subjects
LABORATORY rats, HIGH cholesterol diet, POISONS, WESTERN diet, VETERINARY drugs, RATS
Abstract

Metabolic dysfunction-associated Steatohepatitis (MASH), is a prominent cause for liver cirrhosis. MASH-cirrhosis is responsible for liver complications and there is no specific treatment. To develop new therapeutic approaches, animal models are needed. The aim of this study was to develop a fast animal model of MASH-cirrhosis in rats reflecting the human disease. Carbon tetrachloride (CCl4) injections in combination with a high-fat Western diet (WD) were used to induce MASH-cirrhosis. To accelerate liver injury, animals received phenobarbital (PB) in their drinking water using two different regimens. Rats developed advanced MASH-cirrhosis characterized by portal hypertension, blood biochemistry, hepatic ballooning, steatosis, inflammation and fibrosis. Importantly, rats receiving low-dose PB for the long term (LT) showed ascites after 6 weeks, whereas rats with high-dose short-term (ST) PB developed ascites after 8 weeks. ST- and LT-treated rats showed increased portal pressure (PP) and decreased mean arterial pressure (MAP). Of note, hepatocyte ballooning was only observed in the LT group. The LT administration of low-dose PB with CCl4 intoxication and WD represents a fast and reproducible rat model mimicking decompensated MASH-cirrhosis in humans. Thus, CCl4 + WD with LT low-dose phenobarbital treatment might be the preferred rat animal model for drug development in MASH-cirrhosis. [ABSTRACT FROM AUTHOR]

Published
2024
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29. The clinical course of comorbid substance use disorder and attention deficit/hyperactivity disorder: protocol and clinical characteristics of the INCAS study

Author

Brynte, Christoffer, Aeschlimann, Myriam, Barta, Csaba, Begeman, Alex Hendikus Abraham, Bäcker, Amanda, Crunelle, Cleo Lina, Daigre, Constanza, De Fuentes-Merillas, Laura, Demetrovics, Zsolt, Dom, Geert, López, Lara Grau, Icick, Romain, Johnson, Brian, Joostens, Peter, Kapitány-Fövény, Máté, Karsinti, Emily, Kiefer, Falk, Konstenius, Maija, Levin, Frances R., Luderer, Mathias, Markus, Wiebren, Matthys, Frieda, Moggi, Franz, Palma-Alvarez, Raul Felipe, Paraskevopoulou, Maria, Ramos-Quiroga, J. Antoni, Schellekens, Arnt, Soravia, Leila M., Therribout, Norman, Thomas, Anil, van de Glind, Geurt, van Kernebeek, Michiel Willem, Vollstädt-Klein, Sabine, Vorspan, Florence, van den Brink, Wim, and Franck, Johan

Published
2022
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34. THU-083 Acute kidney injury (AKI) severity in critically-ill patients with decompensated liver cirrhosis and acute-on-chronic liver failure (ACLF)

Author

Schulz, Martin, primary, Wolters, Lena, additional, Jurr, Helen, additional, Gu, Wenyi, additional, Brol, Maximilian Joseph, additional, Uschner, Frank Erhard, additional, Tischendorf, Michael, additional, Buscher, Konrad, additional, Zarbock, Alexander, additional, Schierwagen, Robert, additional, Klein, Sabine, additional, Zeuzem, Stefan, additional, Peiffer, Kai-Henrik, additional, and Trebicka, Jonel, additional

Published
2024
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35. WED-074 The role of endothelial FoxO1 pathway in decompensated liver cirrhosis and acute-on-chronic liver failure

Author

Schachteli, Fabian, primary, Zhang, Yang, additional, Klein, Sabine, additional, Joseph Brol, Maximilian, additional, Schierwagen, Robert, additional, Lembeck, Pia, additional, Noemi Reinartz Groba, Sara, additional, Gu, Wenyi, additional, Zeuzem, Stefan, additional, Trebicka, Jonel, additional, Potente, Michael, additional, and Erhard Uschner, Frank, additional

Published
2024
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36. WED-078 Systemic albumin administration improves the gut microbiome and intestinal permeability in animal models of cirrhosis and ACLF

Author

Phillips, Alexandra, primary, Jin, Yi, additional, Rosenberger, Florian, additional, Zhao, Qianwen, additional, Habtesion, Abeba, additional, Andreola, Fausto, additional, Davies, Nathan, additional, Clasen, Frederick, additional, Edwards, Lindsey, additional, Macnaughtan, Jane, additional, Klein, Sabine, additional, Trebicka, Jonel, additional, Shoaie, Saeed, additional, Mann, Matthias, additional, and Jalan, Rajiv, additional

Published
2024
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38. THU-087 Herpesvirus viremia-cause or consequence of ACLF? Higher prevalence of cytomegalovirus, Epstein-Barr virus and herpes simplex virus viremia in patients with acute-on-chronic liver failure

Author

Sonnenberg, Jannik, primary, Thiyagarajah, Keerthihan, additional, Gorgulu, Esra, additional, Glitscher, Mirco, additional, Kraus, Nico, additional, Wiedemann, Toska, additional, Muecke, Marcus Maximilian, additional, Praktiknjo, Michael, additional, Erasmus, Hans-Peter, additional, Uschner, Frank Erhard, additional, Gu, Wenyi, additional, Brol, Maximilian Joseph, additional, Schulz, Martin, additional, Tischendorf, Michael, additional, Schierwagen, Robert, additional, Klein, Sabine, additional, Vasseur, Jessica, additional, Zeuzem, Stefan, additional, Storf, Holger, additional, Welsch, Christoph, additional, Trebicka, Jonel, additional, Ciesek, Sandra, additional, Hildt, Eberhard, additional, and Peiffer, Kai-Henrik, additional

Published
2024
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39. FRI-039 Terlipressin therapy is associated with increased risk of colonization with multidrug-resistant bacteria in patients with decompensated cirrhosis

Author

Mucke, Marcus, primary, Hernandez-Tejero, Maria, additional, Gu, Wenyi, additional, Kuhn, Michael, additional, Janz, Malte, additional, Isabell Keller, Marisa, additional, Fullam, Anthony, additional, Altepeter, Laura, additional, Mucke, Victoria, additional, Finkelmeier, Fabian, additional, Maria Schwarzkopf, Katharina, additional, Carla, Cremonese, additional, Hunyady, Peter, additional, Heilani, Myriam, additional, Erhard Uschner, Frank, additional, Schierwagen, Robert, additional, Joseph Brol, Maximilian, additional, Klein, Sabine, additional, Peiffer, Kai-Henrik, additional, Hogardt, Michael, additional, Shoaie, Saeed, additional, Coenraad, Minneke, additional, Bojunga, Jörg, additional, Arroyo, Vicente, additional, Zeuzem, Stefan, additional, Kempf, Volkhard A.J., additional, Welsch, Christoph, additional, Laleman, Wim, additional, Bork, Peer, additional, Fernandez, Javier, additional, and Trebicka, Jonel, additional

Published
2024
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40. OS-014-YI Long-term albumin infusion reduces the mortality of cirrhosis and ACLF animal models by modulating the gut-liver axis and hepatic TLR4 signalling

Author

Phillips, Alexandra, primary, Zhao, Qianwen, additional, Habtesion, Abeba, additional, Andreola, Fausto, additional, Davies, Nathan, additional, Edwards, Lindsey, additional, Macnaughtan, Jane, additional, Klein, Sabine, additional, Trebicka, Jonel, additional, and Jalan, Rajiv, additional

Published
2024
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41. WED-126 Biglycan as a biomarker in acute-on-chronic liver failure (ACLF)

Author

Schulz, Martin, primary, Roth, Esther, additional, Zeng-Brouwers, Jinyang, additional, Buscher, Konrad, additional, Schierwagen, Robert, additional, Joseph Brol, Maximilian, additional, Erhard Uschner, Frank, additional, Klein, Sabine, additional, Zeuzem, Stefan, additional, Peiffer, Kai-Henrik, additional, Trebicka, Jonel, additional, and Schaefer, Liliana, additional

Published
2024
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44. International Consensus Statement for the Screening, Diagnosis, and Treatment of Adolescents with Concurrent Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder

Author

Özgen, Heval, Spijkerman, Renske, Noack, Moritz, Holtmann, Martin, Schellekens, Arnt S.A., van de Glind, Geurt, Banaschewski, Tobias, Barta, Csaba, Begeman, Alex, Casas, Miguel, Crunelle, Cleo L., Blanco, Constanza Daigre, Dalsgaard, Søren, Demetrovics, Zsolt, den Boer, Jacomine, Dom, Geert, Eapen, Valsamma, Faraone, Stephen V., Franck, Johan, González, Rafael A., Grau-López, Lara, Groenman, Annabeth P., Hemphälä, Malin, Icick, Romain, Johnson, Brian, Kaess, Michael, Kapitány-Fövény, Máté, Kasinathan, John G., Kaye, Sharlene S., Kiefer, Falk, Konstenius, Maija, Levin, Frances R., Luderer, Mathias, Martinotti, Giovanni, Matthys, Frieda I.A., Meszaros, Gergely, Moggi, Franz, Munasur-Naidoo, Ashmita P., Post, Marianne, Rabinovitz, Sharon, Ramos-Quiroga, Antoni, Sala, Regina, Shafi, Abu, Slobodin, Ortal, Staal, Wouter G., Thomasius, Rainer, Truter, Ilse, van Kernebeek, Michiel W., Velez-Pastrana, Maria C., Vollstädt-Klein, Sabine, Vorspan, Florence, Young, Jesse T., Yule, Amy, van den Brink, Wim, and Hendriks, Vincent

Published
2020

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