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1. Surgical stabilization of rib fractures (SSRF): the WSES and CWIS position paper.

Author

Sermonesi, Giacomo, Bertelli, Riccardo, Pieracci, Fredric, Balogh, Zsolt, Coimbra, Raul, Galante, Joseph, Hecker, Andreas, Weber, Dieter, Bauman, Zachary, Kartiko, Susan, Patel, Bhavik, Whitbeck, SarahAnn, White, Thomas, Harrell, Kevin, Perrina, Daniele, Rampini, Alessia, Tian, Brian, Amico, Francesco, Beka, Solomon, Bonavina, Luigi, Ceresoli, Marco, Cobianchi, Lorenzo, Coccolini, Federico, Cui, Yunfeng, Dal Mas, Francesca, De Simone, Belinda, Di Carlo, Isidoro, Di Saverio, Salomone, Dogjani, Agron, Fette, Andreas, Fraga, Gustavo, Gomes, Carlos, Khan, Jim, Kirkpatrick, Andrew, Kruger, Vitor, Leppäniemi, Ari, Litvin, Andrey, Mingoli, Andrea, Navarro, David, Passera, Eliseo, Pisano, Michele, Podda, Mauro, Russo, Emanuele, Sakakushev, Boris, Santonastaso, Domenico, Sartelli, Massimo, Shelat, Vishal, Tan, Edward, Wani, Imtiaz, Abu-Zidan, Fikri, Biffl, Walter, Civil, Ian, Latifi, Rifat, Marzi, Ingo, Picetti, Edoardo, Pikoulis, Manos, Agnoletti, Vanni, Bravi, Francesca, Vallicelli, Carlo, Ansaloni, Luca, Moore, Ernest, and Catena, Fausto

Subjects
Consensus, Flail chest, Guidelines, Minimally invasive plating osteosynthesis (MIPO), Multiple rib fractures, Operative reduction and internal fixation (ORIF), Rib fixation, Rib fractures, Surgical stabilization of rib fractures (SSRF), Thoracic/chest trauma injury, Video-assisted thoracoscopy surgery (VATS), Rib Fractures, Humans, Fracture Fixation
Abstract

BACKGROUND: Rib fractures are one of the most common traumatic injuries and may result in significant morbidity and mortality. Despite growing evidence, technological advances and increasing acceptance, surgical stabilization of rib fractures (SSRF) remains not uniformly considered in trauma centers. Indications, contraindications, appropriate timing, surgical approaches and utilized implants are part of an ongoing debate. The present position paper, which is endorsed by the World Society of Emergency Surgery (WSES), and supported by the Chest Wall Injury Society, aims to provide a review of the literature investigating the use of SSRF in rib fracture management to develop graded position statements, providing an updated guide and reference for SSRF. METHODS: This position paper was developed according to the WSES methodology. A steering committee performed the literature review and drafted the position paper. An international panel of experts then critically revised the manuscript and discussed it in detail, to develop a consensus on the position statements. RESULTS: A total of 287 studies (systematic reviews, randomized clinical trial, prospective and retrospective comparative studies, case series, original articles) have been selected from an initial pool of 9928 studies. Thirty-nine graded position statements were put forward to address eight crucial aspects of SSRF: surgical indications, contraindications, optimal timing of surgery, preoperative imaging evaluation, rib fracture sites for surgical fixation, management of concurrent thoracic injuries, surgical approach, stabilization methods and material selection. CONCLUSION: This consensus document addresses the key focus questions on surgical treatment of rib fractures. The expert recommendations clarify current evidences on SSRF indications, timing, operative planning, approaches and techniques, with the aim to guide clinicians in optimizing the management of rib fractures, to improve patient outcomes and direct future research.

Published
2024

2. The 2023 WSES guidelines on the management of trauma in elderly and frail patients.

Author

De Simone, Belinda, Chouillard, Elie, Podda, Mauro, Pararas, Nikolaos, de Carvalho Duarte, Gustavo, Fugazzola, Paola, Birindelli, Arianna, Coccolini, Federico, Polistena, Andrea, Sibilla, Maria, Kruger, Vitor, Fraga, Gustavo, Montori, Giulia, Russo, Emanuele, Pintar, Tadeja, Ansaloni, Luca, Avenia, Nicola, Di Saverio, Salomone, Leppäniemi, Ari, Lauretta, Andrea, Sartelli, Massimo, Puzziello, Alessandro, Carcoforo, Paolo, Agnoletti, Vanni, Bissoni, Luca, Isik, Arda, Kluger, Yoram, Moore, Ernest, Romeo, Oreste, Abu-Zidan, Fikri, Beka, Solomon, Weber, Dieter, Tan, Edward, Paolillo, Ciro, Cui, Yunfeng, Kim, Fernando, Picetti, Edoardo, Di Carlo, Isidoro, Toro, Adriana, Sganga, Gabriele, Sganga, Federica, Testini, Mario, Di Meo, Giovanna, Kirkpatrick, Andrew, Marzi, Ingo, déAngelis, Nicola, Kelly, Michael, Wani, Imtiaz, Sakakushev, Boris, Bala, Miklosh, Bonavina, Luigi, Galante, Joseph, Shelat, Vishal, Cobianchi, Lorenzo, Mas, Francesca, Pikoulis, Manos, Damaskos, Dimitrios, Coimbra, Raul, Dhesi, Jugdeep, Hoffman, Melissa, Stahel, Philip, Maier, Ronald, Litvin, Andrey, Latifi, Rifat, Biffl, Walter, and Catena, Fausto

Subjects
Ageing, Antibiotics, Delirium, Direct oral anticoagulants management, Elderly, End of life, Frailty, Geriatric patient, Imaging, Laboratory test, Pain control, Palliative care, Resuscitation, Thrombo-prophylaxis, Trauma management, Trauma score, Vitamin K antagonists anticoagulants management, Humans, Wounds and Injuries, Aged, Frail Elderly, Frailty, Aged, 80 and over, Practice Guidelines as Topic, Geriatric Assessment
Abstract

BACKGROUND: The trauma mortality rate is higher in the elderly compared with younger patients. Ageing is associated with physiological changes in multiple systems and correlated with frailty. Frailty is a risk factor for mortality in elderly trauma patients. We aim to provide evidence-based guidelines for the management of geriatric trauma patients to improve it and reduce futile procedures. METHODS: Six working groups of expert acute care and trauma surgeons reviewed extensively the literature according to the topic and the PICO question assigned. Statements and recommendations were assessed according to the GRADE methodology and approved by a consensus of experts in the field at the 10th international congress of the WSES in 2023. RESULTS: The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage, including drug history, frailty assessment, nutritional status, and early activation of trauma protocol to improve outcomes. Acute trauma pain in the elderly has to be managed in a multimodal analgesic approach, to avoid side effects of opioid use. Antibiotic prophylaxis is recommended in penetrating (abdominal, thoracic) trauma, in severely burned and in open fractures elderly patients to decrease septic complications. Antibiotics are not recommended in blunt trauma in the absence of signs of sepsis and septic shock. Venous thromboembolism prophylaxis with LMWH or UFH should be administrated as soon as possible in high and moderate-risk elderly trauma patients according to the renal function, weight of the patient and bleeding risk. A palliative care team should be involved as soon as possible to discuss the end of life in a multidisciplinary approach considering the patients directives, family feelings and representatives desires, and all decisions should be shared. CONCLUSIONS: The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage based on assessing frailty and early activation of trauma protocol to improve outcomes. Geriatric Intensive Care Units are needed to care for elderly and frail trauma patients in a multidisciplinary approach to decrease mortality and improve outcomes.

Published
2024

3. The NUTRIENT Trial (NUTRitional Intervention among myEloproliferative Neoplasms): Results from a Randomized Phase I Pilot Study for Feasibility and Adherence

Author

Luque, Laura F Mendez, Avelar-Barragan, Julio, Nguyen, Hellen, Nguyen, Jenny, Soyfer, Eli, Li, Jiarui, Chen, Jane, Mehrotra, Nitya, Huang, Xin, Kosiorek, Heidi E, Dueck, Amylou C, Himstead, Alexander S, Heide, Elena S, Lem, Melinda, Alaoui, Kenza El, Mas, Eduard, Scherber, Robyn M, Mesa, Ruben A, Whiteson, Katrine, Odegaard, Andrew, and Fleischman, Angela G

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Hematology, Behavioral and Social Science, Prevention, Complementary and Integrative Health, Dietary Supplements, Nutrition, Clinical Trials and Supportive Activities, Clinical Research, Oral and gastrointestinal, Humans, United States, Pilot Projects, Feasibility Studies, Diet, Mediterranean, Myeloproliferative Disorders, Inflammation, Neoplasms, Nutrients
Abstract

PurposeChronic inflammation is integral to myeloproliferative neoplasm (MPN) pathogenesis. JAK inhibitors reduce cytokine levels, but not without significant side effects. Nutrition is a low-risk approach to reduce inflammation and ameliorate symptoms in MPN. We performed a randomized, parallel-arm study to determine the feasibility of an education-focused Mediterranean diet intervention among patients with MPN.Experimental designWe randomly assigned patients with MPN to either a Mediterranean diet or standard U.S. Dietary Guidelines for Americans (USDA). Groups received equal but separate education with registered dietician counseling and written dietary resources. Patients were prospectively followed for feasibility, adherence, and symptom burden assessments. Biological samples were collected at four timepoints during the 15-week study to explore changes in inflammatory biomarkers and gut microbiome.ResultsThe Mediterranean diet was as easy to follow for patients with MPN as the standard USDA diet. Approximately 80% of the patients in the Mediterranean diet group achieved a Mediterranean Diet Adherence Score of ≥8 throughout the entire active intervention period, whereas less than 50% of the USDA group achieved a score of ≥8 at any timepoint. Improvement in symptom burden was observed in both diet groups. No significant changes were observed in inflammatory cytokines. The diversity and composition of the gut microbiome remained stable throughout the duration of the intervention.ConclusionsWith dietician counseling and written education, patients with MPN can adhere to a Mediterranean eating pattern. Diet interventions may be further developed as a component of MPN care, and potentially incorporated into the management of other hematologic conditions.SignificanceDiet is a central tenant of management of chronic conditions characterized by subclinical inflammation, such as cardiovascular disease, but has not entered the treatment algorithm for clonal hematologic disorders. Here, we establish that a Mediterranean diet intervention is feasible in the MPN patient population and can improve symptom burden. These findings warrant large dietary interventions in patients with hematologic disorders to test the impact of diet on clinical outcomes.

Published
2024

4. Using a chat-based informed consent tool in large-scale genomic research.

Author

Savage, Sarah, LoTempio, Jonathan, Smith, Erica, Andrew, E, Mas, Gloria, Kahn-Kirby, Amanda, Délot, Emmanuèle, Cohen, Andrea, Pitsava, Georgia, Nussbaum, Robert, Fusaro, Vincent, Berger, Seth, and Vilain, Eric

Subjects
chatbot, genetic counseling, genomics, informed consent, large-scale research, Humans, Prospective Studies, Informed Consent, Genomics, Software, Communication
Abstract

OBJECTIVE: We implemented a chatbot consent tool to shift the time burden from study staff in support of a national genomics research study. MATERIALS AND METHODS: We created an Institutional Review Board-approved script for automated chat-based consent. We compared data from prospective participants who used the tool or had traditional consent conversations with study staff. RESULTS: Chat-based consent, completed on a users schedule, was shorter than the traditional conversation. This did not lead to a significant change in affirmative consents. Within affirmative consents and declines, more prospective participants completed the chat-based process. A quiz to assess chat-based consent user understanding had a high pass rate with no reported negative experiences. CONCLUSION: Our report shows that a structured script can convey important information while realizing the benefits of automation and burden shifting. Analysis suggests that it may be advantageous to use chatbots to scale this rate-limiting step in large research projects.

Published
2024

5. Cesena guidelines: WSES consensus statement on laparoscopic-first approach to general surgery emergencies and abdominal trauma.

Author

Sermonesi, Giacomo, Tian, Brian, Vallicelli, Carlo, Abu-Zidan, Fikri, Damaskos, Dimitris, Kelly, Michael, Leppäniemi, Ari, Galante, Joseph, Tan, Edward, Kirkpatrick, Andrew, Khokha, Vladimir, Romeo, Oreste, Chirica, Mircea, Pikoulis, Manos, Litvin, Andrey, Shelat, Vishal, Sakakushev, Boris, Wani, Imtiaz, Sall, Ibrahima, Fugazzola, Paola, Cicuttin, Enrico, Toro, Adriana, Amico, Francesco, Mas, Francesca, De Simone, Belinda, Sugrue, Michael, Bonavina, Luigi, Campanelli, Giampiero, Carcoforo, Paolo, Cobianchi, Lorenzo, Coccolini, Federico, Chiarugi, Massimo, Di Carlo, Isidoro, Di Saverio, Salomone, Podda, Mauro, Pisano, Michele, Sartelli, Massimo, Testini, Mario, Fette, Andreas, Rizoli, Sandro, Picetti, Edoardo, Weber, Dieter, Latifi, Rifat, Kluger, Yoram, Balogh, Zsolt, Biffl, Walter, Jeekel, Hans, Civil, Ian, Hecker, Andreas, Ansaloni, Luca, Bravi, Francesca, Agnoletti, Vanni, Beka, Solomon, Moore, Ernest, and Catena, Fausto

Subjects
Acute appendicitis, Acute care surgery, Acute cholecystitis, Acute diverticulitis, Acute pancreatitis, Acute peritonitis, Adhesive small bowel obstruction, Colo–rectal emergencies, Emergency general surgery, Guidelines, Incarcerated/complicated ventral/inguinal hernia, Laparoscopic approach, Laparoscopy, Mesenteric ischemia, Minimally invasive surgery/approach, Penetrating/blunt abdominal trauma, Perforated peptic ulcer, Recommendations, Trauma surgery hemodynamic stability, Humans, Emergencies, Retrospective Studies, Laparoscopy, Abdomen, Abdominal Injuries, Randomized Controlled Trials as Topic
Abstract

BACKGROUND: Laparoscopy is widely adopted across nearly all surgical subspecialties in the elective setting. Initially finding indication in minor abdominal emergencies, it has gradually become the standard approach in the majority of elective general surgery procedures. Despite many technological advances and increasing acceptance, the laparoscopic approach remains underutilized in emergency general surgery and in abdominal trauma. Emergency laparotomy continues to carry a high morbidity and mortality. In recent years, there has been a growing interest from emergency and trauma surgeons in adopting minimally invasive surgery approaches in the acute surgical setting. The present position paper, supported by the World Society of Emergency Surgery (WSES), aims to provide a review of the literature to reach a consensus on the indications and benefits of a laparoscopic-first approach in patients requiring emergency abdominal surgery for general surgery emergencies or abdominal trauma. METHODS: This position paper was developed according to the WSES methodology. A steering committee performed the literature review and drafted the position paper. An international panel of 54 experts then critically revised the manuscript and discussed it in detail, to develop a consensus on a position statement. RESULTS: A total of 323 studies (systematic review and meta-analysis, randomized clinical trial, retrospective comparative cohort studies, case series) have been selected from an initial pool of 7409 studies. Evidence demonstrates several benefits of the laparoscopic approach in stable patients undergoing emergency abdominal surgery for general surgical emergencies or abdominal trauma. The selection of a stable patient seems to be of paramount importance for a safe adoption of a laparoscopic approach. In hemodynamically stable patients, the laparoscopic approach was found to be safe, feasible and effective as a therapeutic tool or helpful to identify further management steps and needs, resulting in improved outcomes, regardless of conversion. Appropriate patient selection, surgeon experience and rigorous minimally invasive surgical training, remain crucial factors to increase the adoption of laparoscopy in emergency general surgery and abdominal trauma. CONCLUSIONS: The WSES expert panel suggests laparoscopy as the first approach for stable patients undergoing emergency abdominal surgery for general surgery emergencies and abdominal trauma.

Published
2023

6. The functional connectome in obsessive-compulsive disorder: resting-state mega-analysis and machine learning classification for the ENIGMA-OCD consortium.

Author

Bruin, Willem, Abe, Yoshinari, Alonso, Pino, Anticevic, Alan, Backhausen, Lea, Balachander, Srinivas, Bargallo, Nuria, Batistuzzo, Marcelo, Benedetti, Francesco, Bertolin Triquell, Sara, Brem, Silvia, Calesella, Federico, Couto, Beatriz, Denys, Damiaan, Echevarria, Marco, Eng, Goi, Ferreira, Sónia, Feusner, Jamie, Grazioplene, Rachael, Gruner, Patricia, Guo, Joyce, Hagen, Kristen, Hansen, Bjarne, Hirano, Yoshiyuki, Hoexter, Marcelo, Jahanshad, Neda, Jaspers-Fayer, Fern, Kasprzak, Selina, Kim, Minah, Koch, Kathrin, Bin Kwak, Yoo, Kwon, Jun, Lazaro, Luisa, Li, Chiang-Shan, Lochner, Christine, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Menchon, Jose, Moreira, Pedro, Morgado, Pedro, Nakagawa, Akiko, Nakao, Tomohiro, Narayanaswamy, Janardhanan, Nurmi, Erika, Zorrilla, Jose, Picó-Pérez, Maria, Piras, Fabrizio, Piras, Federica, Pittenger, Christopher, Reddy, Janardhan, Rodriguez-Manrique, Daniela, Sakai, Yuki, Shimizu, Eiji, Shivakumar, Venkataram, Simpson, Blair, Soriano-Mas, Carles, Sousa, Nuno, Spalletta, Gianfranco, Stern, Emily, Evelyn Stewart, S, Szeszko, Philip, Tang, Jinsong, Thomopoulos, Sophia, Thorsen, Anders, Yoshida, Tokiko, Tomiyama, Hirofumi, Vai, Benedetta, Veer, Ilya, Venkatasubramanian, Ganesan, Vetter, Nora, Vriend, Chris, Walitza, Susanne, Waller, Lea, Wang, Zhen, Watanabe, Anri, Wolff, Nicole, Yun, Je-Yeon, Zhao, Qing, van Leeuwen, Wieke, van Marle, Hein, van de Mortel, Laurens, van der Straten, Anouk, van der Werf, Ysbrand, Thompson, Paul, Stein, Dan, van den Heuvel, Odile, van Wingen, Guido, and Piacentini, John

Subjects
Humans, Connectome, Brain Mapping, Magnetic Resonance Imaging, Brain, Obsessive-Compulsive Disorder, Biomarkers, Neural Pathways
Abstract

Current knowledge about functional connectivity in obsessive-compulsive disorder (OCD) is based on small-scale studies, limiting the generalizability of results. Moreover, the majority of studies have focused only on predefined regions or functional networks rather than connectivity throughout the entire brain. Here, we investigated differences in resting-state functional connectivity between OCD patients and healthy controls (HC) using mega-analysis of data from 1024 OCD patients and 1028 HC from 28 independent samples of the ENIGMA-OCD consortium. We assessed group differences in whole-brain functional connectivity at both the regional and network level, and investigated whether functional connectivity could serve as biomarker to identify patient status at the individual level using machine learning analysis. The mega-analyses revealed widespread abnormalities in functional connectivity in OCD, with global hypo-connectivity (Cohens d: -0.27 to -0.13) and few hyper-connections, mainly with the thalamus (Cohens d: 0.19 to 0.22). Most hypo-connections were located within the sensorimotor network and no fronto-striatal abnormalities were found. Overall, classification performances were poor, with area-under-the-receiver-operating-characteristic curve (AUC) scores ranging between 0.567 and 0.673, with better classification for medicated (AUC = 0.702) than unmedicated (AUC = 0.608) patients versus healthy controls. These findings provide partial support for existing pathophysiological models of OCD and highlight the important role of the sensorimotor network in OCD. However, resting-state connectivity does not so far provide an accurate biomarker for identifying patients at the individual level.

Published
2023

7. ECLAPTE: Effective Closure of LAParoTomy in Emergency-2023 World Society of Emergency Surgery guidelines for the closure of laparotomy in emergency settings.

Author

Frassini, Simone, Cobianchi, Lorenzo, Fugazzola, Paola, Biffl, Walter, Coccolini, Federico, Damaskos, Dimitrios, Moore, Ernest, Kluger, Yoram, Ceresoli, Marco, Coimbra, Raul, Davies, Justin, Kirkpatrick, Andrew, Di Carlo, Isidoro, Hardcastle, Timothy, Isik, Arda, Chiarugi, Massimo, Gurusamy, Kurinchi, Maier, Ronald, Segovia Lohse, Helmut, Jeekel, Hans, Boermeester, Marja, Abu-Zidan, Fikri, Inaba, Kenji, Weber, Dieter, Augustin, Goran, Bonavina, Luigi, Velmahos, George, Sartelli, Massimo, Di Saverio, Salomone, Ten Broek, Richard, Granieri, Stefano, Dal Mas, Francesca, Farè, Camilla, Peverada, Jacopo, Zanghì, Simone, Viganò, Jacopo, Tomasoni, Matteo, Dominioni, Tommaso, Cicuttin, Enrico, Hecker, Andreas, Tebala, Giovanni, Galante, Joseph, Wani, Imtiaz, Khokha, Vladimir, Sugrue, Michael, Scalea, Thomas, Tan, Edward, Malangoni, Mark, Pararas, Nikolaos, Podda, Mauro, De Simone, Belinda, Ivatury, Rao, Cui, Yunfeng, Kashuk, Jeffry, Peitzman, Andrew, Kim, Fernando, Pikoulis, Emmanouil, Sganga, Gabriele, Chiara, Osvaldo, Kelly, Michael, Marzi, Ingo, Picetti, Edoardo, Agnoletti, Vanni, DeAngelis, Nicola, Campanelli, Giampiero, de Moya, Marc, Litvin, Andrey, Martínez-Pérez, Aleix, Sall, Ibrahima, Rizoli, Sandro, Tomadze, Gia, Sakakushev, Boris, Stahel, Philip, Civil, Ian, Shelat, Vishal, Costa, David, Chichom-Mefire, Alain, Latifi, Rifat, Chirica, Mircea, Amico, Francesco, Pardhan, Amyn, Seenarain, Vidya, Boyapati, Nikitha, Hatz, Basil, Ackermann, Travis, Abeyasundara, Sandun, Fenton, Linda, Plani, Frank, Sarvepalli, Rohit, Rouhbakhshfar, Omid, Caleo, Pamela, Ho-Ching Yau, Victor, Clement, Kristenne, Christou, Erasmia, Castillo, Ana, Gosal, Preet, Balasubramaniam, Sunder, Hsu, Jeremy, Banphawatanarak, Kamon, and Pisano, Michele

Subjects
Abdominal wall incision, Closure technique, Emergency, Incisional hernia, Laparotomy closure, Midline incision, Wound complications, Wound dehiscence, Humans, Laparotomy, Abdominal Wound Closure Techniques, Suture Techniques, Incisional Hernia, Reoperation
Abstract

Laparotomy incisions provide easy and rapid access to the peritoneal cavity in case of emergency surgery. Incisional hernia (IH) is a late manifestation of the failure of abdominal wall closure and represents frequent complication of any abdominal incision: IHs can cause pain and discomfort to the patients but also clinical serious sequelae like bowel obstruction, incarceration, strangulation, and necessity of reoperation. Previous guidelines and indications in the literature consider elective settings and evidence about laparotomy closure in emergency settings is lacking. This paper aims to present the World Society of Emergency Surgery (WSES) project called ECLAPTE (Effective Closure of LAParoTomy in Emergency): the final manuscript includes guidelines on the closure of emergency laparotomy.

Published
2023

8. Right Prefrontal Cortical Thickness Is Associated With Response to Cognitive-Behavioral Therapy in Children With Obsessive-Compulsive Disorder.

Author

Bertolín, Sara, Alonso, Pino, Martínez-Zalacaín, Ignacio, Menchón, Jose, Jimenez-Murcia, Susana, Baker, Justin, Bargalló, Nuria, Batistuzzo, Marcelo, Boedhoe, Premika, Brennan, Brian, Feusner, Jamie, Fitzgerald, Kate, Fontaine, Martine, Hansen, Bjarne, Hirano, Yoshiyuki, Hoexter, Marcelo, Huyser, Chaim, Jahanshad, Neda, Jaspers-Fayer, Fern, Kuno, Masaru, Kvale, Gerd, Lazaro, Luisa, Machado-Sousa, Mafalda, Marsh, Rachel, Morgado, Pedro, Nakagawa, Akiko, Norman, Luke, Nurmi, Erika, ONeill, Joseph, Ortiz, Ana, Perriello, Chris, Picó-Pérez, Maria, Shavitt, Roseli, Shimizu, Eiji, Simpson, Helen, Stewart, S, Thomopoulos, Sophia, Thorsen, Anders, Walitza, Susanne, Wolters, Lidewij, Thompson, Paul, van den Heuvel, Odile, Stein, Dan, Soriano-Mas, Carles, and Piacentini, John

Subjects
anxiety disorders, cognitive-behavioral therapy, magnetic resonance imaging, neuroimaging, obsessive-compulsive disorder, Adult, Adolescent, Humans, Child, Child, Preschool, Prefrontal Cortex, Obsessive-Compulsive Disorder, Magnetic Resonance Imaging, Frontal Lobe, Cognitive Behavioral Therapy
Abstract

OBJECTIVE: Cognitive-behavioral therapy (CBT) is considered a first-line treatment for obsessive-compulsive disorder (OCD) in pediatric and adult populations. Nevertheless, some patients show partial or null response. The identification of predictors of CBT response may improve clinical management of patients with OCD. Here, we aimed to identify structural magnetic resonance imaging (MRI) predictors of CBT response in 2 large series of children and adults with OCD from the worldwide ENIGMA-OCD consortium. METHOD: Data from 16 datasets from 13 international sites were included in the study. We assessed which variations in baseline cortical thickness, cortical surface area, and subcortical volume predicted response to CBT (percentage of baseline to post-treatment symptom reduction) in 2 samples totaling 168 children and adolescents (age range 5-17.5 years) and 318 adult patients (age range 18-63 years) with OCD. Mixed linear models with random intercept were used to account for potential cross-site differences in imaging values. RESULTS: Significant results were observed exclusively in the pediatric sample. Right prefrontal cortex thickness was positively associated with the percentage of CBT response. In a post hoc analysis, we observed that the specific changes accounting for this relationship were a higher thickness of the frontal pole and the rostral middle frontal gyrus. We observed no significant effects of age, sex, or medication on our findings. CONCLUSION: Higher cortical thickness in specific right prefrontal cortex regions may be important for CBT response in children with OCD. Our findings suggest that the right prefrontal cortex plays a relevant role in the mechanisms of action of CBT in children.

Published
2023

9. The 2021 SIIM-FISABIO-RSNA Machine Learning COVID-19 Challenge: Annotation and Standard Exam Classification of COVID-19 Chest Radiographs.

Author

Lakhani, Paras, Mongan, J, Singhal, C, Zhou, Q, Andriole, K, Auffermann, W, Prasanna, P, Pham, T, Peterson, Michael, Bergquist, P, Cook, T, Ferraciolli, S, Corradi, G, Takahashi, M, Workman, C, Parekh, M, Kamel, S, Galant, J, Mas-Sanchez, A, Benítez, E, Sánchez-Valverde, M, Jaques, L, Panadero, M, Vidal, M, Culiañez-Casas, M, Angulo-Gonzalez, D, Langer, S, de la Iglesia-Vayá, María, and Shih, G

Subjects
Artificial Intelligence, COVID-19, Machine Learning, Pneumonia, Radiography, Thorax, Humans, COVID-19, Artificial Intelligence, Radiography, Machine Learning, Radiologists, Radiography, Thoracic
Abstract

We describe the curation, annotation methodology, and characteristics of the dataset used in an artificial intelligence challenge for detection and localization of COVID-19 on chest radiographs. The chest radiographs were annotated by an international group of radiologists into four mutually exclusive categories, including typical, indeterminate, and atypical appearance for COVID-19, or negative for pneumonia, adapted from previously published guidelines, and bounding boxes were placed on airspace opacities. This dataset and respective annotations are available to researchers for academic and noncommercial use.

Published
2023

10. Deconvoluting complex correlates of COVID-19 severity with a multi-omic pandemic tracking strategy

Author

Parikh, Victoria N, Ioannidis, Alexander G, Jimenez-Morales, David, Gorzynski, John E, De Jong, Hannah N, Liu, Xiran, Roque, Jonasel, Cepeda-Espinoza, Victoria P, Osoegawa, Kazutoyo, Hughes, Chris, Sutton, Shirley C, Youlton, Nathan, Joshi, Ruchi, Amar, David, Tanigawa, Yosuke, Russo, Douglas, Wong, Justin, Lauzon, Jessie T, Edelson, Jacob, Mas Montserrat, Daniel, Kwon, Yongchan, Rubinacci, Simone, Delaneau, Olivier, Cappello, Lorenzo, Kim, Jaehee, Shoura, Massa J, Raja, Archana N, Watson, Nathaniel, Hammond, Nathan, Spiteri, Elizabeth, Mallempati, Kalyan C, Montero-Martín, Gonzalo, Christle, Jeffrey, Kim, Jennifer, Kirillova, Anna, Seo, Kinya, Huang, Yong, Zhao, Chunli, Moreno-Grau, Sonia, Hershman, Steven G, Dalton, Karen P, Zhen, Jimmy, Kamm, Jack, Bhatt, Karan D, Isakova, Alina, Morri, Maurizio, Ranganath, Thanmayi, Blish, Catherine A, Rogers, Angela J, Nadeau, Kari, Yang, Samuel, Blomkalns, Andra, O’Hara, Ruth, Neff, Norma F, DeBoever, Christopher, Szalma, Sándor, Wheeler, Matthew T, Gates, Christian M, Farh, Kyle, Schroth, Gary P, Febbo, Phil, deSouza, Francis, Cornejo, Omar E, Fernandez-Vina, Marcelo, Kistler, Amy, Palacios, Julia A, Pinsky, Benjamin A, Bustamante, Carlos D, Rivas, Manuel A, and Ashley, Euan A

Subjects
Biological Sciences, Genetics, Pneumonia & Influenza, Lung, Prevention, Human Genome, Clinical Research, Infectious Diseases, Infection, Good Health and Well Being, COVID-19, Genome, Viral, Genome-Wide Association Study, Humans, Pandemics, SARS-CoV-2
Abstract

The SARS-CoV-2 pandemic has differentially impacted populations across race and ethnicity. A multi-omic approach represents a powerful tool to examine risk across multi-ancestry genomes. We leverage a pandemic tracking strategy in which we sequence viral and host genomes and transcriptomes from nasopharyngeal swabs of 1049 individuals (736 SARS-CoV-2 positive and 313 SARS-CoV-2 negative) and integrate them with digital phenotypes from electronic health records from a diverse catchment area in Northern California. Genome-wide association disaggregated by admixture mapping reveals novel COVID-19-severity-associated regions containing previously reported markers of neurologic, pulmonary and viral disease susceptibility. Phylodynamic tracking of consensus viral genomes reveals no association with disease severity or inferred ancestry. Summary data from multiomic investigation reveals metagenomic and HLA associations with severe COVID-19. The wealth of data available from residual nasopharyngeal swabs in combination with clinical data abstracted automatically at scale highlights a powerful strategy for pandemic tracking, and reveals distinct epidemiologic, genetic, and biological associations for those at the highest risk.

Published
2022

11. An overview of the first 5 years of the ENIGMA obsessive–compulsive disorder working group: The power of worldwide collaboration

Author

van den Heuvel, Odile A, Boedhoe, Premika SW, Bertolin, Sara, Bruin, Willem B, Francks, Clyde, Ivanov, Iliyan, Jahanshad, Neda, Kong, Xiang‐Zhen, Kwon, Jun Soo, O'Neill, Joseph, Paus, Tomas, Patel, Yash, Piras, Fabrizio, Schmaal, Lianne, Soriano‐Mas, Carles, Spalletta, Gianfranco, van Wingen, Guido A, Yun, Je‐Yeon, Vriend, Chris, Simpson, H Blair, van Rooij, Daan, Hoexter, Marcelo Q, Hoogman, Martine, Buitelaar, Jan K, Arnold, Paul, Beucke, Jan C, Benedetti, Francesco, Bollettini, Irene, Bose, Anushree, Brennan, Brian P, De Nadai, Alessandro S, Fitzgerald, Kate, Gruner, Patricia, Grünblatt, Edna, Hirano, Yoshiyuki, Huyser, Chaim, James, Anthony, Koch, Kathrin, Kvale, Gerd, Lazaro, Luisa, Lochner, Christine, Marsh, Rachel, Mataix‐Cols, David, Morgado, Pedro, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C, Nurmi, Erika, Pittenger, Christopher, Reddy, YC Janardhan, Sato, João R, Soreni, Noam, Stewart, S Evelyn, Taylor, Stephan F, Tolin, David, Thomopoulos, Sophia I, Veltman, Dick J, Venkatasubramanian, Ganesan, Walitza, Susanne, Wang, Zhen, Thompson, Paul M, Stein, Dan J, Abe, Yoshinari, Alonso, Pino, Assogna, Francesca, Banaj, Nerisa, Batistuzzo, Marcelo C, Brem, Silvia, Ciullo, Valentina, Feusner, Jamie, Martínez‐Zalacaín, Ignacio, Menchón, José M, Miguel, Euripedes C, Piacentini, John, Piras, Federica, Sakai, Yuki, Wolters, Lidewij, and Yamada, Kei

Subjects
Biological Psychology, Psychology, Brain Disorders, Clinical Research, Serious Mental Illness, Pediatric, Neurosciences, Mental Health, Mental health, Neurological, Cerebral Cortex, Humans, Machine Learning, Multicenter Studies as Topic, Neuroimaging, Obsessive-Compulsive Disorder, cortical thickness, ENIGMA, mega-analysis, meta-analysis, MRI, obsessive-compulsive disorder, surface area, volume, ENIGMA-OCD working group, Cognitive Sciences, Experimental Psychology, Biological psychology, Cognitive and computational psychology
Abstract

Neuroimaging has played an important part in advancing our understanding of the neurobiology of obsessive-compulsive disorder (OCD). At the same time, neuroimaging studies of OCD have had notable limitations, including reliance on relatively small samples. International collaborative efforts to increase statistical power by combining samples from across sites have been bolstered by the ENIGMA consortium; this provides specific technical expertise for conducting multi-site analyses, as well as access to a collaborative community of neuroimaging scientists. In this article, we outline the background to, development of, and initial findings from ENIGMA's OCD working group, which currently consists of 47 samples from 34 institutes in 15 countries on 5 continents, with a total sample of 2,323 OCD patients and 2,325 healthy controls. Initial work has focused on studies of cortical thickness and subcortical volumes, structural connectivity, and brain lateralization in children, adolescents and adults with OCD, also including the study on the commonalities and distinctions across different neurodevelopment disorders. Additional work is ongoing, employing machine learning techniques. Findings to date have contributed to the development of neurobiological models of OCD, have provided an important model of global scientific collaboration, and have had a number of clinical implications. Importantly, our work has shed new light on questions about whether structural and functional alterations found in OCD reflect neurodevelopmental changes, effects of the disease process, or medication impacts. We conclude with a summary of ongoing work by ENIGMA-OCD, and a consideration of future directions for neuroimaging research on OCD within and beyond ENIGMA.

Published
2022

12. Identifying sex-specific differences in the carotid revascularisation literature: findings from a scoping review

Author

Yogendrakumar, Vignan, Shamy, Michel, Dewar, Brian, Fergusson, Dean A, Dowlatshahi, Dar, Hamel, Candyce, Gocan, Sophia, Fedyk, Mark, Mas, Jean-Louis, Rothwell, Peter, Howard, Virginia, and Bereznyakova, Olena

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Patient Safety, Clinical Trials and Supportive Activities, Stroke, Brain Disorders, 7.3 Management and decision making, Management of diseases and conditions, Cardiovascular, Carotid Arteries, Carotid Stenosis, Endarterectomy, Carotid, Female, Humans, Male, Stents, Treatment Outcome, atherosclerosis, intervention, stenosis, stent, WoW-CAD Investigators
Abstract

ObjectiveNo systematic review of the literature has dedicated itself to looking at the management of symptomatic carotid stenosis in female patients. In this scoping review, we aimed to identify all randomised controlled trials (RCTs) that reported sex-specific outcomes for patients who underwent carotid revascularisation, and determine whether sufficient information is reported within these studies to assess short-term and long-term outcomes in female patients.Design, setting and participantsWe systematically searched Medline, Embase, Pubmed and Cochrane libraries for RCTs published between 1991 and 2020 that included female patients and compared either endarterectomy with stenting, or any revascularisation (endarterectomy or stenting) with medical therapy in patients with symptomatic high-grade (>50%) carotid stenosis.ResultsFrom 1537 references examined, 27 eligible studies were identified. Sex-specific outcomes were reported in 13 studies. Baseline patient characteristics of enrolled female patients were reported in 2 of those 13 studies. Common outcomes reported included stroke and death, however, there was significant heterogeneity in the reporting of both periprocedural and long-term outcomes. Sex-specific differences relating to the degree of stenosis and time from index event to treatment are largely limited to studies comparing endarterectomy to medical therapy. Adverse events were not reported by sex.ConclusionsOnly half of the previously published RCTs and systematic reviews report sex-specific outcomes. Detailed analyses on the results of carotid artery intervention for female patients with symptomatic stenosis are limited.

Published
2021

13. PIAS1 modulates striatal transcription, DNA damage repair, and SUMOylation with relevance to Huntington’s disease

Author

Morozko, Eva L, Smith-Geater, Charlene, Monteys, Alejandro Mas, Pradhan, Subrata, Lim, Ryan G, Langfelder, Peter, Kachemov, Marketta, Kulkarni, Jayesh A, Zaifman, Josh, Hill, Austin, Stocksdale, Jennifer T, Cullis, Pieter R, Wu, Jie, Ochaba, Joseph, Miramontes, Ricardo, Chakraborty, Anirban, Hazra, Tapas K, Lau, Alice, St-cyr, Sophie, Orellana, Iliana, Kopan, Lexi, Wang, Keona Q, Yeung, Sylvia, Leavitt, Blair R, Reidling, Jack C, Yang, X William, Steffan, Joan S, Davidson, Beverly L, Sarkar, Partha S, and Thompson, Leslie M

Subjects
Biochemistry and Cell Biology, Genetics, Biological Sciences, Neurosciences, Huntington's Disease, Brain Disorders, Neurodegenerative, Stem Cell Research, Rare Diseases, Underpinning research, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Aetiology, Neurological, Animals, Cell Differentiation, DNA, DNA Damage, DNA Repair, DNA Repair Enzymes, Disease Models, Animal, Female, Humans, Huntingtin Protein, Huntington Disease, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Phosphotransferases (Alcohol Group Acceptor), Pluripotent Stem Cells, Primary Cell Culture, Protein Inhibitors of Activated STAT, Protein Processing, Post-Translational, RNA, Small Interfering, Small Ubiquitin-Related Modifier Proteins, Sumoylation, Transcription, Genetic, DNA damage repair, SUMO, PIAS, Huntington's disease, PNKP
Abstract

DNA damage repair genes are modifiers of disease onset in Huntington's disease (HD), but how this process intersects with associated disease pathways remains unclear. Here we evaluated the mechanistic contributions of protein inhibitor of activated STAT-1 (PIAS1) in HD mice and HD patient-derived induced pluripotent stem cells (iPSCs) and find a link between PIAS1 and DNA damage repair pathways. We show that PIAS1 is a component of the transcription-coupled repair complex, that includes the DNA damage end processing enzyme polynucleotide kinase-phosphatase (PNKP), and that PIAS1 is a SUMO E3 ligase for PNKP. Pias1 knockdown (KD) in HD mice had a normalizing effect on HD transcriptional dysregulation associated with synaptic function and disease-associated transcriptional coexpression modules enriched for DNA damage repair mechanisms as did reduction of PIAS1 in HD iPSC-derived neurons. KD also restored mutant HTT-perturbed enzymatic activity of PNKP and modulated genomic integrity of several transcriptionally normalized genes. The findings here now link SUMO modifying machinery to DNA damage repair responses and transcriptional modulation in neurodegenerative disease.

Published
2021

14. Correlates of trichomoniasis among female sex workers who inject drugs in two Mexico-US border cities.

Author

West, Brooke S, Becerra Ramirez, Milagros, Bristow, Claire C, Abramovitz, Daniela A, Vera, Alicia, Staines, Hugo, Gudelia Rangel, M, Patterson, Thomas L, Strathdee, Steffanie A, and for Proyecto Mujer Mas Segura

Subjects
for Proyecto Mujer Mas Segura, Humans, Trichomonas Infections, Substance Abuse, Intravenous, Methamphetamine, Risk Factors, Unsafe Sex, Violence, Adolescent, Adult, Mexico, United States, Female, Sex Workers, Sex Work, Trichomoniasis, female sex workers, injection drug use, methamphetamine, police violence, sexually transmitted infections, Drug Abuse (NIDA Only), Substance Abuse, Sexually Transmitted Infections, HIV/AIDS, Public Health, Clinical Sciences, Medical Microbiology, Public Health and Health Services
Abstract

This paper evaluates correlates of trichomoniasis among female sex workers who inject drugs (FSWIDs) in two Mexico-US border cities. HIV-negative FSWIDs aged 18 years or older were enrolled in a study between 2008 and 2010 in Tijuana and Ciudad Juarez (Cd.), Mexico. All participants underwent a baseline interviewer-administered survey and did a rapid test for trichomoniasis. Using regression to estimate prevalence ratios, we examined sociodemographics, sex work characteristics, sexual health and behavior, substance use, and police and violence exposures as potential correlates of trichomoniasis. Of 584 women (284 in Tijuana, 300 in Cd. Juarez), prevalence of trichomoniasis was 33.6%. Factors associated with trichomoniasis in multivariable analysis were having money stolen by police in the past six months (adjusted prevalence ratio [aPR] =1.448, 95% confidence interval [CI] = 1.152-1.821), recent methamphetamine use (aPR = 1.432, CI = 1.055-1.944), lifetime syphilis infection (aPR = 1.360, CI = 1.061-1.743), ever use of a home remedy to treat vaginal symptoms (aPR = 1.301, CI = 1.027-1.649), and number of regular clients in the past month (aPR = 1.006 per client, CI = 1.004-1.009), while controlling for age and city of interview. Alongside the need for trichomoniasis surveillance and treatment programs, findings indicate that both structural and behavioral factors serve as primary correlates of trichomoniasis among FSWIDs in these cities.

Published
2020

15. Proposal for Updated Nomenclature and Classification of Potential Causative Mechanism in Patent Foramen Ovale–Associated Stroke

Author

Elgendy, Akram Y, Saver, Jeffrey L, Amin, Zahid, Boudoulas, Konstantinos Dean, Carroll, John D, Elgendy, Islam Y, Grunwald, Iris Q, Gertz, Zachary M, Hijazi, Ziyad M, Horlick, Eric M, Kasner, Scott E, Kent, David M, Kumar, Preetham, Kavinsky, Clifford J, Liebeskind, David S, Lutsep, Helmi, Mojadidi, Mohammad K, Messé, Steven R, Mas, Jean-Louis, Mattle, Heinrich P, Meier, Bernhard, Mahmoud, Ahmad, Mahmoud, Ahmed N, Nietlispach, Fabian, Patel, Nimesh K, Rhodes, John F, Reisman, Mark, Sommer, Robert J, Sievert, Horst, Søndergaard, Lars, Zaman, Muhammad O, Thaler, David, and Tobis, Jonathan M

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Stroke, Hematology, Brain Disorders, Foramen Ovale, Patent, Humans, Ischemic Stroke, Terminology as Topic
Abstract

ImportanceRecent epidemiologic and therapeutic advances have transformed understanding of the role of and therapeutic approach to patent foramen ovale (PFO) in ischemic stroke. Patent foramen ovale is likely responsible for approximately 5% of all ischemic strokes and 10% of those occurring in young and middle-aged adults.ObservationsRandomized clinical trials have demonstrated that, to prevent recurrent ischemic stroke in patients with PFO and an otherwise-cryptogenic index ischemic stroke, PFO closure is superior to antiplatelet medical therapy alone; these trials have provided some evidence that, among medical therapy options, anticoagulants may be more effective than antiplatelet agents.Conclusions and relevanceThese new data indicate a need to update classification schemes of causative mechanisms in stroke, developed in an era in which an association between PFO and stroke was viewed as uncertain. We propose a revised general nomenclature and classification framework for PFO-associated stroke and detailed revisions for the 3 major stroke subtyping algorithms in wide use.

Published
2020

16. Mapping Cortical and Subcortical Asymmetry in Obsessive-Compulsive Disorder: Findings From the ENIGMA Consortium

Author

Kong, Xiang-Zhen, Boedhoe, Premika SW, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H, Arnold, Paul D, Assogna, Francesca, Baker, Justin T, Batistuzzo, Marcelo C, Benedetti, Francesco, Beucke, Jan C, Bollettini, Irene, Bose, Anushree, Brem, Silvia, Brennan, Brian P, Buitelaar, Jan, Calvo, Rosa, Cheng, Yuqi, Cho, Kang Ik K, Dallaspezia, Sara, Denys, Damiaan, Ely, Benjamin A, Feusner, Jamie, Fitzgerald, Kate D, Fouche, Jean-Paul, Fridgeirsson, Egill A, Glahn, David C, Gruner, Patricia, Gürsel, Deniz A, Hauser, Tobias U, Hirano, Yoshiyuki, Hoexter, Marcelo Q, Hu, Hao, Huyser, Chaim, James, Anthony, Jaspers-Fayer, Fern, Kathmann, Norbert, Kaufmann, Christian, Koch, Kathrin, Kuno, Masaru, Kvale, Gerd, Kwon, Jun Soo, Lazaro, Luisa, Liu, Yanni, Lochner, Christine, Marques, Paulo, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Medland, Sarah E, Menchón, José M, Minuzzi, Luciano, Moreira, Pedro S, Morer, Astrid, Morgado, Pedro, Nakagawa, Akiko, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C, Nurmi, Erika L, O'Neill, Joseph, Pariente, Jose C, Perriello, Chris, Piacentini, John, Piras, Fabrizio, Piras, Federica, Pittenger, Christopher, Reddy, YC Janardhan, Rus-Oswald, Oana Georgiana, Sakai, Yuki, Sato, Joao R, Schmaal, Lianne, Simpson, H Blair, Soreni, Noam, Soriano-Mas, Carles, Spalletta, Gianfranco, Stern, Emily R, Stevens, Michael C, Stewart, S Evelyn, Szeszko, Philip R, Tolin, David F, Tsuchiyagaito, Aki, van Rooij, Daan, van Wingen, Guido A, Venkatasubramanian, Ganesan, Wang, Zhen, Yun, Je-Yeon, Group, ENIGMA OCD Working, Anticevic, Alan, Banaj, Nerisa, and Bargalló, Nuria

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Psychology, Serious Mental Illness, Mental Health, Neurosciences, Brain Disorders, Clinical Research, Anxiety Disorders, Neurological, Mental health, Adult, Brain, Brain Mapping, Child, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Obsessive-Compulsive Disorder, Thalamus, Brain asymmetry, Laterality, Mega-analysis, Obsessive-compulsive disorder, Pallidum, ENIGMA OCD Working Group, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Biological sciences, Biomedical and clinical sciences
Abstract

BackgroundLateralized dysfunction has been suggested in obsessive-compulsive disorder (OCD). However, it is currently unclear whether OCD is characterized by abnormal patterns of brain structural asymmetry. Here we carried out what is by far the largest study of brain structural asymmetry in OCD.MethodsWe studied a collection of 16 pediatric datasets (501 patients with OCD and 439 healthy control subjects), as well as 30 adult datasets (1777 patients and 1654 control subjects) from the OCD Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium. Asymmetries of the volumes of subcortical structures, and of measures of regional cortical thickness and surface areas, were assessed based on T1-weighted magnetic resonance imaging scans, using harmonized image analysis and quality control protocols. We investigated possible alterations of brain asymmetry in patients with OCD. We also explored potential associations of asymmetry with specific aspects of the disorder and medication status.ResultsIn the pediatric datasets, the largest case-control differences were observed for volume asymmetry of the thalamus (more leftward; Cohen's d = 0.19) and the pallidum (less leftward; d = -0.21). Additional analyses suggested putative links between these asymmetry patterns and medication status, OCD severity, or anxiety and depression comorbidities. No significant case-control differences were found in the adult datasets.ConclusionsThe results suggest subtle changes of the average asymmetry of subcortical structures in pediatric OCD, which are not detectable in adults with the disorder. These findings may reflect altered neurodevelopmental processes in OCD.

Published
2020

17. ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.

Author

Thompson, Paul M, Jahanshad, Neda, Ching, Christopher RK, Salminen, Lauren E, Thomopoulos, Sophia I, Bright, Joanna, Baune, Bernhard T, Bertolín, Sara, Bralten, Janita, Bruin, Willem B, Bülow, Robin, Chen, Jian, Chye, Yann, Dannlowski, Udo, de Kovel, Carolien GF, Donohoe, Gary, Eyler, Lisa T, Faraone, Stephen V, Favre, Pauline, Filippi, Courtney A, Frodl, Thomas, Garijo, Daniel, Gil, Yolanda, Grabe, Hans J, Grasby, Katrina L, Hajek, Tomas, Han, Laura KM, Hatton, Sean N, Hilbert, Kevin, Ho, Tiffany C, Holleran, Laurena, Homuth, Georg, Hosten, Norbert, Houenou, Josselin, Ivanov, Iliyan, Jia, Tianye, Kelly, Sinead, Klein, Marieke, Kwon, Jun Soo, Laansma, Max A, Leerssen, Jeanne, Lueken, Ulrike, Nunes, Abraham, Neill, Joseph O', Opel, Nils, Piras, Fabrizio, Piras, Federica, Postema, Merel C, Pozzi, Elena, Shatokhina, Natalia, Soriano-Mas, Carles, Spalletta, Gianfranco, Sun, Daqiang, Teumer, Alexander, Tilot, Amanda K, Tozzi, Leonardo, van der Merwe, Celia, Van Someren, Eus JW, van Wingen, Guido A, Völzke, Henry, Walton, Esther, Wang, Lei, Winkler, Anderson M, Wittfeld, Katharina, Wright, Margaret J, Yun, Je-Yeon, Zhang, Guohao, Zhang-James, Yanli, Adhikari, Bhim M, Agartz, Ingrid, Aghajani, Moji, Aleman, André, Althoff, Robert R, Altmann, Andre, Andreassen, Ole A, Baron, David A, Bartnik-Olson, Brenda L, Marie Bas-Hoogendam, Janna, Baskin-Sommers, Arielle R, Bearden, Carrie E, Berner, Laura A, Boedhoe, Premika SW, Brouwer, Rachel M, Buitelaar, Jan K, Caeyenberghs, Karen, Cecil, Charlotte AM, Cohen, Ronald A, Cole, James H, Conrod, Patricia J, De Brito, Stephane A, de Zwarte, Sonja MC, Dennis, Emily L, Desrivieres, Sylvane, Dima, Danai, Ehrlich, Stefan, Esopenko, Carrie, Fairchild, Graeme, Fisher, Simon E, Fouche, Jean-Paul, and Francks, Clyde

Subjects
ENIGMA Consortium, Brain, Humans, Magnetic Resonance Imaging, Reproducibility of Results, Depressive Disorder, Major, Neuroimaging, Neurosciences, Clinical Research, Mental Health, Brain Disorders, Behavioral and Social Science, Genetics, Basic Behavioral and Social Science, Prevention, 2.1 Biological and endogenous factors, 2.3 Psychological, social and economic factors, Mental health, Neurological, Clinical Sciences, Public Health and Health Services, Psychology
Abstract

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.

Published
2020

18. Brain structural covariance networks in obsessive-compulsive disorder: a graph analysis from the ENIGMA Consortium

Author

Yun, Je-Yeon, Boedhoe, Premika SW, Vriend, Chris, Jahanshad, Neda, Abe, Yoshinari, Ameis, Stephanie H, Anticevic, Alan, Arnold, Paul D, Batistuzzo, Marcelo C, Benedetti, Francesco, Beucke, Jan C, Bollettini, Irene, Bose, Anushree, Brem, Silvia, Calvo, Anna, Cheng, Yuqi, Cho, Kang Ik K, Ciullo, Valentina, Dallaspezia, Sara, Denys, Damiaan, Feusner, Jamie D, Fouche, Jean-Paul, Giménez, Mònica, Gruner, Patricia, Hibar, Derrek P, Hoexter, Marcelo Q, Hu, Hao, Huyser, Chaim, Ikari, Keisuke, Kathmann, Norbert, Kaufmann, Christian, Koch, Kathrin, Lazaro, Luisa, Lochner, Christine, Marques, Paulo, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Menchón, José M, Minuzzi, Luciano, Morgado, Pedro, Moreira, Pedro, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C, Nurmi, Erika L, O’Neill, Joseph, Piacentini, John, Piras, Fabrizio, Piras, Federica, Reddy, YC Janardhan, Sato, Joao R, Simpson, H Blair, Soreni, Noam, Soriano-Mas, Carles, Spalletta, Gianfranco, Stevens, Michael C, Szeszko, Philip R, Tolin, David F, Venkatasubramanian, Ganesan, Walitza, Susanne, Wang, Zhen, van Wingen, Guido A, Xu, Jian, Xu, Xiufeng, Zhao, Qing, van den Heuvel, Odile3 A, Stein, Dan J, Thompson, Paul M, Ik, Kang, and Cho, K

Subjects
Mental Health, Brain Disorders, Serious Mental Illness, Clinical Research, Neurosciences, Neurological, Mental health, Adult, Brain, Cerebral Cortex, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Neural Pathways, Obsessive-Compulsive Disorder, brain structural covariance network, graph theory, obsessive-compulsive disorder, pharmacotherapy, illness duration, ENIGMA-OCD working group, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract

Brain structural covariance networks reflect covariation in morphology of different brain areas and are thought to reflect common trajectories in brain development and maturation. Large-scale investigation of structural covariance networks in obsessive-compulsive disorder (OCD) may provide clues to the pathophysiology of this neurodevelopmental disorder. Using T1-weighted MRI scans acquired from 1616 individuals with OCD and 1463 healthy controls across 37 datasets participating in the ENIGMA-OCD Working Group, we calculated intra-individual brain structural covariance networks (using the bilaterally-averaged values of 33 cortical surface areas, 33 cortical thickness values, and six subcortical volumes), in which edge weights were proportional to the similarity between two brain morphological features in terms of deviation from healthy controls (i.e. z-score transformed). Global networks were characterized using measures of network segregation (clustering and modularity), network integration (global efficiency), and their balance (small-worldness), and their community membership was assessed. Hub profiling of regional networks was undertaken using measures of betweenness, closeness, and eigenvector centrality. Individually calculated network measures were integrated across the 37 datasets using a meta-analytical approach. These network measures were summated across the network density range of K = 0.10-0.25 per participant, and were integrated across the 37 datasets using a meta-analytical approach. Compared with healthy controls, at a global level, the structural covariance networks of OCD showed lower clustering (P

Published
2020

19. Structural neuroimaging biomarkers for obsessive-compulsive disorder in the ENIGMA-OCD consortium: medication matters

Author

Bruin, Willem B, Taylor, Luke, Thomas, Rajat M, Shock, Jonathan P, Zhutovsky, Paul, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H, Anticevic, Alan, Arnold, Paul D, Assogna, Francesca, Benedetti, Francesco, Beucke, Jan C, Boedhoe, Premika SW, Bollettini, Irene, Bose, Anushree, Brem, Silvia, Brennan, Brian P, Buitelaar, Jan K, Calvo, Rosa, Cheng, Yuqi, Cho, Kang Ik K, Dallaspezia, Sara, Denys, Damiaan, Ely, Benjamin A, Feusner, Jamie D, Fitzgerald, Kate D, Fouche, Jean-Paul, Fridgeirsson, Egill A, Gruner, Patricia, Gürsel, Deniz A, Hauser, Tobias U, Hirano, Yoshiyuki, Hoexter, Marcelo Q, Hu, Hao, Huyser, Chaim, Ivanov, Iliyan, James, Anthony, Jaspers-Fayer, Fern, Kathmann, Norbert, Kaufmann, Christian, Koch, Kathrin, Kuno, Masaru, Kvale, Gerd, Kwon, Jun Soo, Liu, Yanni, Lochner, Christine, Lázaro, Luisa, Marques, Paulo, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Menchón, José M, Minuzzi, Luciano, Moreira, Pedro S, Morer, Astrid, Morgado, Pedro, Nakagawa, Akiko, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C, Nurmi, Erika L, O’Neill, Joseph, Pariente, Jose C, Perriello, Chris, Piacentini, John, Piras, Fabrizio, Piras, Federica, Reddy, YC Janardhan, Rus-Oswald, Oana G, Sakai, Yuki, Sato, João R, Schmaal, Lianne, Shimizu, Eiji, Simpson, H Blair, Soreni, Noam, Soriano-Mas, Carles, Spalletta, Gianfranco, Stern, Emily R, Stevens, Michael C, Stewart, S Evelyn, Szeszko, Philip R, Tolin, David F, Venkatasubramanian, Ganesan, Wang, Zhen, Yun, Je-Yeon, van Rooij, Daan, Thompson, Paul M, van den Heuvel, Odile A, Stein, Dan J, and van Wingen, Guido A

Subjects
Mental Health, Biomedical Imaging, Serious Mental Illness, Brain Disorders, Neurosciences, Clinical Research, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Mental health, Biomarkers, Brain, Humans, Magnetic Resonance Imaging, Neuroimaging, Obsessive-Compulsive Disorder, ENIGMA-OCD Working Group, Clinical Sciences, Public Health and Health Services, Psychology
Abstract

No diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Here, we aimed to identify magnetic resonance imaging (MRI) biomarkers for OCD, using 46 data sets with 2304 OCD patients and 2068 healthy controls from the ENIGMA consortium. We performed machine learning analysis of regional measures of cortical thickness, surface area and subcortical volume and tested classification performance using cross-validation. Classification performance for OCD vs. controls using the complete sample with different classifiers and cross-validation strategies was poor. When models were validated on data from other sites, model performance did not exceed chance-level. In contrast, fair classification performance was achieved when patients were grouped according to their medication status. These results indicate that medication use is associated with substantial differences in brain anatomy that are widely distributed, and indicate that clinical heterogeneity contributes to the poor performance of structural MRI as a disease marker.

Published
2020

20. Associations of Perioperative Variables With the 30-Day Risk of Stroke or Death in Carotid Endarterectomy for Symptomatic Carotid Stenosis.

Author

Knappich, Christoph, Kuehnl, Andreas, Haller, Bernhard, Salvermoser, Michael, Algra, Ale, Becquemin, Jean-Pierre, Bonati, Leo H, Bulbulia, Richard, Calvet, David, Fraedrich, Gustav, Gregson, John, Halliday, Alison, Hendrikse, Jeroen, Howard, George, Jansen, Olav, Malas, Mahmoud B, Ringleb, Peter A, Brown, Martin M, Mas, Jean-Louis, Brott, Thomas G, Morris, Dylan R, Lewis, Steff C, and Eckstein, Hans-Henning

Subjects
Humans, Carotid Stenosis, Postoperative Complications, Anesthesia, Local, Anesthesia, General, Endarterectomy, Carotid, Risk Factors, Aged, Middle Aged, Female, Male, Stroke, anesthesia, death, endarterectomy, carotid, humans, stroke, Clinical Research, Neurosciences, Brain Disorders, endarterectomy, carotid, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Neurology & Neurosurgery
Abstract

Background and Purpose- This analysis was performed to assess the association between perioperative and clinical variables and the 30-day risk of stroke or death after carotid endarterectomy for symptomatic carotid stenosis. Methods- Individual patient-level data from the 5 largest randomized controlled carotid trials were pooled in the Carotid Stenosis Trialists' Collaboration database. A total of 4181 patients who received carotid endarterectomy for symptomatic stenosis per protocol were included. Determinants of outcome included carotid endarterectomy technique, type of anesthesia, intraoperative neurophysiological monitoring, shunting, antiplatelet medication, and clinical variables. Stroke or death within 30 days after carotid endarterectomy was the primary outcome. Adjusted risk ratios (aRRs) were estimated in multilevel multivariable analyses using a Poisson regression model. Results- Mean age was 69.5±9.2 years (70.7% men). The 30-day stroke or death rate was 4.3%. In the multivariable regression analysis, local anesthesia was associated with a lower primary outcome rate (versus general anesthesia; aRR, 0.70 [95% CI, 0.50-0.99]). Shunting (aRR, 1.43 [95% CI, 1.05-1.95]), a contralateral high-grade carotid stenosis or occlusion (aRR, 1.58 [95% CI, 1.02-2.47]), and a more severe neurological deficit (mRS, 3-5 versus 0-2: aRR, 2.51 [95% CI, 1.30-4.83]) were associated with higher primary outcome rates. None of the other characteristics were significantly associated with the perioperative stroke or death risk. Conclusions- The current results indicate lower perioperative stroke or death rates in patients operated upon under local anesthesia, whereas a more severe neurological deficit and a contralateral high-grade carotid stenosis or occlusion were identified as potential risk factors. Despite a possible selection bias and patients not having been randomized, these findings might be useful to guide surgeons and anesthetists when treating patients with symptomatic carotid disease.

Published
2019

21. Resting-State Functional Connectivity Magnetic Resonance Imaging and Outcome After Acute Stroke.

Author

Puig, Josep, Blasco, Gerard, Alberich-Bayarri, Angel, Schlaug, Gottfried, Deco, Gustavo, Biarnes, Carles, Navas-Martí, Marian, Rivero, Mireia, Gich, Jordi, Figueras, Jaume, Torres, Cristina, Daunis-I-Estadella, Pepus, Oramas-Requejo, Celia, Serena, Joaquín, Stinear, Cathy, Kuceyeski, Amy, Soriano-Mas, Carles, Thomalla, Götz, Essig, Marco, Figley, Chase, Menon, Bijoy, Demchuk, Andrew, Wintermark, Max, Liebeskind, David, Pedraza, Salvador, and Nael, Kambiz

Subjects
brain, magnetic resonance imaging, patients, reperfusion, stroke, Aged, Aged, 80 and over, Brain, Brain Ischemia, Female, Functional Laterality, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Stroke
Abstract

Background and Purpose- Physiological effects of stroke are best assessed over entire brain networks rather than just focally at the site of structural damage. Resting-state functional magnetic resonance imaging can map functional-anatomic networks by analyzing spontaneously correlated low-frequency activity fluctuations across the brain, but its potential usefulness in predicting functional outcome after acute stroke remains unknown. We assessed the ability of resting-state functional magnetic resonance imaging to predict functional outcome after acute stroke. Methods- We scanned 37 consecutive reperfused stroke patients (age, 69±14 years; 14 females; 3-day National Institutes of Health Stroke Scale score, 6±5) on day 3 after symptom onset. After imaging preprocessing, we used a whole-brain mask to calculate the correlation coefficient matrices for every paired region using the Harvard-Oxford probabilistic atlas. To evaluate functional outcome, we applied the modified Rankin Scale at 90 days. We used region of interest analyses to explore the functional connectivity between regions and graph-computation analysis to detect differences in functional connectivity between patients with good functional outcome (modified Rankin Scale score ≤2) and those with poor outcome (modified Rankin Scale score >2). Results- Patients with good outcome had greater functional connectivity than patients with poor outcome. Although 3-day National Institutes of Health Stroke Scale score was the most accurate independent predictor of 90-day modified Rankin Scale (84.2%), adding functional connectivity increased accuracy to 94.7%. Preserved bilateral interhemispheric connectivity between the anterior inferior temporal gyrus and superior frontal gyrus and decreased connectivity between the caudate and anterior inferior temporal gyrus in the left hemisphere had the greatest impact in favoring good prognosis. Conclusions- These data suggest that information about functional connectivity from resting-state functional magnetic resonance imaging may help predict 90-day stroke outcome.

Published
2018

22. Cortical Abnormalities Associated With Pediatric and Adult Obsessive-Compulsive Disorder: Findings From the ENIGMA Obsessive-Compulsive Disorder Working Group

Author

Boedhoe, Premika SW, Schmaal, Lianne, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H, Anticevic, Alan, Arnold, Paul D, Batistuzzo, Marcelo C, Benedetti, Francesco, Beucke, Jan C, Bollettini, Irene, Bose, Anushree, Brem, Silvia, Calvo, Anna, Calvo, Rosa, Cheng, Yuqi, Cho, Kang Ik K, Ciullo, Valentina, Dallaspezia, Sara, Denys, Damiaan, Feusner, Jamie D, Fitzgerald, Kate D, Fouche, Jean-Paul, Fridgeirsson, Egill A, Gruner, Patricia, Hanna, Gregory L, Hibar, Derrek P, Hoexter, Marcelo Q, Hu, Hao, Huyser, Chaim, Jahanshad, Neda, James, Anthony, Kathmann, Norbert, Kaufmann, Christian, Koch, Kathrin, Kwon, Jun Soo, Lazaro, Luisa, Lochner, Christine, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Menchón, José M, Minuzzi, Luciano, Morer, Astrid, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C, Nishida, Seiji, Nurmi, Erika, O’Neill, Joseph, Piacentini, John, Piras, Fabrizio, Piras, Federica, Reddy, YC Janardhan, Reess, Tim J, Sakai, Yuki, Sato, Joao R, Simpson, H Blair, Soreni, Noam, Soriano-Mas, Carles, Spalletta, Gianfranco, Stevens, Michael C, Szeszko, Philip R, Tolin, David F, van Wingen, Guido A, Venkatasubramanian, Ganesan, Walitza, Susanne, Wang, Zhen, Yun, Je-Yeon, Thompson, Paul M, Stein, Dan J, van den Heuvel, Odile A, Bargalló, Nuria, Brandeis, Daniel, Buimer, Elizabeth, Busatto, Geraldo F, de Vries, Froukje E, de Wit, Stella J, Drechsler, Renate, and Falini, Andrea

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Psychology, Pediatric, Neurosciences, Mental Health, Serious Mental Illness, Brain Disorders, Neurological, Mental health, Adolescent, Adult, Age of Onset, Cerebral Cortex, Child, Frontal Lobe, Humans, Magnetic Resonance Imaging, Obsessive-Compulsive Disorder, Parietal Lobe, Reference Values, Temporal Lobe, Young Adult, ENIGMA-OCD Working Group, ENIGMA OCD Working Group, Cortical Thickness, FreeSurfer, MRI, Surface Area, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Clinical and health psychology
Abstract

ObjectiveBrain imaging studies of structural abnormalities in OCD have yielded inconsistent results, partly because of limited statistical power, clinical heterogeneity, and methodological differences. The authors conducted meta- and mega-analyses comprising the largest study of cortical morphometry in OCD ever undertaken.MethodT1-weighted MRI scans of 1,905 OCD patients and 1,760 healthy controls from 27 sites worldwide were processed locally using FreeSurfer to assess cortical thickness and surface area. Effect sizes for differences between patients and controls, and associations with clinical characteristics, were calculated using linear regression models controlling for age, sex, site, and intracranial volume.ResultsIn adult OCD patients versus controls, we found a significantly lower surface area for the transverse temporal cortex and a thinner inferior parietal cortex. Medicated adult OCD patients also showed thinner cortices throughout the brain. In pediatric OCD patients compared with controls, we found significantly thinner inferior and superior parietal cortices, but none of the regions analyzed showed significant differences in surface area. However, medicated pediatric OCD patients had lower surface area in frontal regions. Cohen's d effect sizes varied from -0.10 to -0.33.ConclusionsThe parietal cortex was consistently implicated in both adults and children with OCD. More widespread cortical thickness abnormalities were found in medicated adult OCD patients, and more pronounced surface area deficits (mainly in frontal regions) were found in medicated pediatric OCD patients. These cortical measures represent distinct morphological features and may be differentially affected during different stages of development and illness, and possibly moderated by disease profile and medication.

Published
2018

23. Living Close to Natural Outdoor Environments in Four European Cities: Adults’ Contact with the Environments and Physical Activity

Author

Triguero-Mas, Margarita, Donaire-Gonzalez, David, Seto, Edmund, Valentín, Antònia, Smith, Graham, Martínez, David, Carrasco-Turigas, Glòria, Masterson, Daniel, van den Berg, Magdalena, Ambròs, Albert, Martínez-Íñiguez, Tania, Dedele, Audrius, Hurst, Gemma, Ellis, Naomi, Grazulevicius, Tomas, Voorsmit, Martin, Cirach, Marta, Cirac-Claveras, Judith, Swart, Wim, Clasquin, Eddy, Maas, Jolanda, Wendel-Vos, Wanda, Jerrett, Michael, Gražulevičienė, Regina, Kruize, Hanneke, Gidlow, Christopher J, and Nieuwenhuijsen, Mark J

Subjects
Human Geography, Public Health, Health Sciences, Human Society, Clinical Research, Sustainable Cities and Communities, Adult, Cities, Cross-Sectional Studies, Environment, Environment Design, Europe, Exercise, Female, Geographic Information Systems, Humans, Male, Residence Characteristics, green spaces, physical activity, natural outdoor environments, Toxicology
Abstract

This study investigated whether residential availability of natural outdoor environments (NOE) was associated with contact with NOE, overall physical activity and physical activity in NOE, in four different European cities using objective measures. A nested cross-sectional study was conducted in Barcelona (Spain); Stoke-on-Trent (United Kingdom); Doetinchem (The Netherlands); and Kaunas (Lithuania). Smartphones were used to collect information on the location and physical activity (overall and NOE) of around 100 residents of each city over seven days. We used Geographic Information Systems (GIS) to determine residential NOE availability (presence/absence of NOE within 300 m buffer from residence), contact with NOE (time spent in NOE), overall PA (total physical activity), NOE PA (total physical activity in NOE). Potential effect modifiers were investigated. Participants spent around 40 min in NOE and 80 min doing overall PA daily, of which 11% was in NOE. Having residential NOE availability was consistently linked with higher NOE contact during weekdays, but not to overall PA. Having residential NOE availability was related to NOE PA, especially for our Barcelona participants, people that lived in a city with low NOE availability.

Published
2017

24. Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition

Author

Mateo, F, Arenas, EJ, Aguilar, H, Serra-Musach, J, de Garibay, G Ruiz, Boni, J, Maicas, M, Du, S, Iorio, F, Herranz-Ors, C, Islam, A, Prado, X, Llorente, A, Petit, A, Vidal, A, Català, I, Soler, T, Venturas, G, Rojo-Sebastian, A, Serra, H, Cuadras, D, Blanco, I, Lozano, J, Canals, F, Sieuwerts, AM, de Weerd, V, Look, MP, Puertas, S, García, N, Perkins, AS, Bonifaci, N, Skowron, M, Gómez-Baldó, L, Hernández, V, Martínez-Aranda, A, Martínez-Iniesta, M, Serrat, X, Cerón, J, Brunet, J, Barretina, MP, Gil, M, Falo, C, Fernández, A, Morilla, I, Pernas, S, Plà, MJ, Andreu, X, Seguí, MA, Ballester, R, Castellà, E, Nellist, M, Morales, S, Valls, J, Velasco, A, Matias-Guiu, X, Figueras, A, Sánchez-Mut, JV, Sánchez-Céspedes, M, Cordero, A, Gómez-Miragaya, J, Palomero, L, Gómez, A, Gajewski, TF, Cohen, EEW, Jesiotr, M, Bodnar, L, Quintela-Fandino, M, López-Bigas, N, Valdés-Mas, R, Puente, XS, Viñals, F, Casanovas, O, Graupera, M, Hernández-Losa, J, Ramón y Cajal, S, García-Alonso, L, Saez-Rodriguez, J, Esteller, M, Sierra, A, Martín-Martín, N, Matheu, A, Carracedo, A, González-Suárez, E, Nanjundan, M, Cortés, J, Lázaro, C, Odero, MD, Martens, JWM, Moreno-Bueno, G, Barcellos-Hoff, MH, Villanueva, A, Gomis, RR, and Pujana, MA

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Breast Cancer, Stem Cell Research, Adaptor Proteins, Signal Transducing, Adult, Aged, Breast Neoplasms, Carrier Proteins, Cell Proliferation, DNA-Binding Proteins, Female, Gene Expression Regulation, Neoplastic, Humans, Lung Neoplasms, MCF-7 Cells, MDS1 and EVI1 Complex Locus Protein, Microfilament Proteins, Middle Aged, Neoplasm Metastasis, Osteonectin, Proto-Oncogenes, Regulatory-Associated Protein of mTOR, SOX9 Transcription Factor, Signal Transduction, TOR Serine-Threonine Kinases, Transcription Factors, Xenograft Model Antitumor Assays, Clinical Sciences, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure.

Published
2017

25. PIAS1 Regulates Mutant Huntingtin Accumulation and Huntington’s Disease-Associated Phenotypes In Vivo

Author

Ochaba, Joseph, Monteys, Alex Mas, O’Rourke, Jacqueline G, Reidling, Jack C, Steffan, Joan S, Davidson, Beverly L, and Thompson, Leslie M

Subjects
Biomedical and Clinical Sciences, Neurosciences, Brain Disorders, Neurodegenerative, Huntington's Disease, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, Neurological, Animals, Brain, Disease Models, Animal, Humans, Huntingtin Protein, Huntington Disease, Mice, Mutation, Nerve Tissue Proteins, Neurons, Nuclear Proteins, Phenotype, Protein Inhibitors of Activated STAT, Small Ubiquitin-Related Modifier Proteins, Psychology, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

The disruption of protein quality control networks is central to pathology in Huntington's disease (HD) and other neurodegenerative disorders. The aberrant accumulation of insoluble high-molecular-weight protein complexes containing the Huntingtin (HTT) protein and SUMOylated protein corresponds to disease manifestation. We previously identified an HTT-selective E3 SUMO ligase, PIAS1, that regulates HTT accumulation and SUMO modification in cells. Here we investigated whether PIAS1 modulation in neurons alters HD-associated phenotypes in vivo. Instrastriatal injection of a PIAS1-directed miRNA significantly improved behavioral phenotypes in rapidly progressing mutant HTT (mHTT) fragment R6/2 mice. PIAS1 reduction prevented the accumulation of mHTT and SUMO- and ubiquitin-modified proteins, increased synaptophysin levels, and normalized key inflammatory markers. In contrast, PIAS1 overexpression exacerbated mHTT-associated phenotypes and aberrant protein accumulation. These results confirm the association between aberrant accumulation of expanded polyglutamine-dependent insoluble protein species and pathogenesis, and they link phenotypic benefit to reduction of these species through PIAS1 modulation.

Published
2016

26. Predictors of Injection Cessation and Relapse among Female Sex Workers who Inject Drugs in Two Mexican-US Border Cities

Author

West, Brooke S, Abramovitz, Daniela, Staines, Hugo, Vera, Alicia, Patterson, Thomas L, Strathdee, Steffanie A, and for Proyecto Mujer Mas Segura

Subjects
Public Health, Health Sciences, HIV/AIDS, Substance Misuse, Prevention, Behavioral and Social Science, Infectious Diseases, Clinical Research, Sexually Transmitted Infections, Drug Abuse (NIDA only), Women's Health, Good Health and Well Being, Adult, Age Factors, Cities, Female, Humans, Mexico, Proportional Hazards Models, Recurrence, Risk Factors, Sex Workers, Sexual Behavior, Substance Abuse, Intravenous, Time Factors, Urban Health, Injection drug use, Cessation, Relapse, Female sex work, Methadone maintenance, Treatment, Proyecto Mujer Mas Segura, Human Movement and Sports Sciences, Public Health and Health Services, Public health
Abstract

We know little about predictors of injection drug cessation and relapse among female sex workers who inject drugs (FSW-PWID) at the US-Mexico border. Among HIV-negative FSW-PWID taking part in a behavioral intervention study in Tijuana and Ciudad Juárez, Cox regression was used to identify predictors of time to first cessation of injection, which was defined as reporting not having injected drugs for a period of 4 months or longer, and among that subset, we examined predictors of time to injection relapse. Among 440 women, 84 (19%) reported ceasing injection during follow-up (median time to cessation = 9.3 months); of these, 30 (35%) reported relapse to injection (median time to relapse = 3.5 months). The rate of injection cessation was lower for women reporting trading sex prior to age 18 (adj. hazard ratio (HR) = 0.64, 95% confidence interval (CI) = 0.41-1.01), ever being sexually abused (adj. HR = 0.44, 95% CI = 0.27-0.71), and a higher number of vaginal sex acts with casual clients (adj. HR = 0.99 per transaction, 95% CI = 0.98-1.00). The rate of cessation was higher for women who spent more hours on the streets on a typical day (adj. HR = 1.04/h, 95% CI = 1.01-1.08) and who lived in Tijuana vs. Ciudad Juárez (adj. HR = 2.15, 95% CI = 1.14-4.07). The rate of relapse was higher among women reporting regular drug use with clients (adj. HR = 2.17, 95% CI = 0.96-4.89) and those scoring higher on a risk injection index (adj. HR = 2.04, 95% CI = 1.15-3.61). The rate of relapse was lower for FSW-PWID with higher than average incomes (adj. HR = 0.40, 95% CI = 0.18-0.89). These findings have important implications for the scale-up of methadone maintenance treatment programs (MMTPs) in Mexico and indicate a need for gender-specific programs that address sexual abuse experiences and economic vulnerabilities faced by FSW-PWID.

Published
2016

27. A comprehensive assessment of somatic mutation detection in cancer using whole-genome sequencing.

Author

Alioto, Tyler S, Buchhalter, Ivo, Derdak, Sophia, Hutter, Barbara, Eldridge, Matthew D, Hovig, Eivind, Heisler, Lawrence E, Beck, Timothy A, Simpson, Jared T, Tonon, Laurie, Sertier, Anne-Sophie, Patch, Ann-Marie, Jäger, Natalie, Ginsbach, Philip, Drews, Ruben, Paramasivam, Nagarajan, Kabbe, Rolf, Chotewutmontri, Sasithorn, Diessl, Nicolle, Previti, Christopher, Schmidt, Sabine, Brors, Benedikt, Feuerbach, Lars, Heinold, Michael, Gröbner, Susanne, Korshunov, Andrey, Tarpey, Patrick S, Butler, Adam P, Hinton, Jonathan, Jones, David, Menzies, Andrew, Raine, Keiran, Shepherd, Rebecca, Stebbings, Lucy, Teague, Jon W, Ribeca, Paolo, Giner, Francesc Castro, Beltran, Sergi, Raineri, Emanuele, Dabad, Marc, Heath, Simon C, Gut, Marta, Denroche, Robert E, Harding, Nicholas J, Yamaguchi, Takafumi N, Fujimoto, Akihiro, Nakagawa, Hidewaki, Quesada, Víctor, Valdés-Mas, Rafael, Nakken, Sigve, Vodák, Daniel, Bower, Lawrence, Lynch, Andrew G, Anderson, Charlotte L, Waddell, Nicola, Pearson, John V, Grimmond, Sean M, Peto, Myron, Spellman, Paul, He, Minghui, Kandoth, Cyriac, Lee, Semin, Zhang, John, Létourneau, Louis, Ma, Singer, Seth, Sahil, Torrents, David, Xi, Liu, Wheeler, David A, López-Otín, Carlos, Campo, Elías, Campbell, Peter J, Boutros, Paul C, Puente, Xose S, Gerhard, Daniela S, Pfister, Stefan M, McPherson, John D, Hudson, Thomas J, Schlesner, Matthias, Lichter, Peter, Eils, Roland, Jones, David TW, and Gut, Ivo G

Subjects
Humans, Medulloblastoma, Mutation, Genome, Human, Leukemia, Lymphoid, High-Throughput Nucleotide Sequencing, Genome, Human, Leukemia, Lymphoid
Abstract

As whole-genome sequencing for cancer genome analysis becomes a clinical tool, a full understanding of the variables affecting sequencing analysis output is required. Here using tumour-normal sample pairs from two different types of cancer, chronic lymphocytic leukaemia and medulloblastoma, we conduct a benchmarking exercise within the context of the International Cancer Genome Consortium. We compare sequencing methods, analysis pipelines and validation methods. We show that using PCR-free methods and increasing sequencing depth to ∼ 100 × shows benefits, as long as the tumour:control coverage ratio remains balanced. We observe widely varying mutation call rates and low concordance among analysis pipelines, reflecting the artefact-prone nature of the raw data and lack of standards for dealing with the artefacts. However, we show that, using the benchmark mutation set we have created, many issues are in fact easy to remedy and have an immediate positive impact on mutation detection accuracy.

Published
2015

28. A prospective comparison of alginate-hydrogel with standard medical therapy to determine impact on functional capacity and clinical outcomes in patients with advanced heart failure (AUGMENT-HF trial).

Author

Anker, Stefan, Coats, Andrew, Cristian, Gabriel, Dragomir, Dinu, Pusineri, Enrico, Piredda, Massimo, Bettari, Luca, Dowling, Robert, Volterrani, Maurizio, Kirwan, Bridget-Anne, Filippatos, Gerasimos, Mas, Jean-Louis, Danchin, Nicolas, Solomon, Scott, Ahmann, Frank, Hinson, Andy, Sabbah, Hani, Mann, Douglas, and Lee, Randall

Subjects
Advanced chronic heart failure, Alginate-hydrogel, Exercise capacity, Safety, Symptoms, Alginates, Echocardiography, Exercise Test, Exercise Tolerance, Female, Glucuronic Acid, Heart Failure, Hexuronic Acids, Humans, Hydrogel, Polyethylene Glycol Dimethacrylate, Length of Stay, Male, Middle Aged, Oxygen Consumption, Patient Safety, Prospective Studies, Prostheses and Implants, Quality of Life, Treatment Outcome, Walking
Abstract

AIMS: AUGMENT-HF was an international, multi-centre, prospective, randomized, controlled trial to evaluate the benefits and safety of a novel method of left ventricular (LV) modification with alginate-hydrogel. METHODS: Alginate-hydrogel is an inert permanent implant that is directly injected into LV heart muscle and serves as a prosthetic scaffold to modify the shape and size of the dilated LV. Patients with advanced chronic heart failure (HF) were randomized (1 : 1) to alginate-hydrogel (n = 40) in combination with standard medical therapy or standard medical therapy alone (Control, n = 38). The primary endpoint of AUGMENT-HF was the change in peak VO2 from baseline to 6 months. Secondary endpoints included changes in 6-min walk test (6MWT) distance and New York Heart Association (NYHA) functional class, as well as assessments of procedural safety. RESULTS: Enrolled patients were 63 ± 10 years old, 74% in NYHA functional class III, had a LV ejection fraction of 26 ± 5% and a mean peak VO2 of 12.2 ± 1.8 mL/kg/min. Thirty-five patients were successfully treated with alginate-hydrogel injections through a limited left thoracotomy approach without device-related complications; the 30-day surgical mortality was 8.6% (3 deaths). Alginate-hydrogel treatment was associated with improved peak VO2 at 6 months-treatment effect vs. CONTROL: +1.24 mL/kg/min (95% confidence interval 0.26-2.23, P = 0.014). Also 6MWT distance and NYHA functional class improved in alginate-hydrogel-treated patients vs. Control (both P < 0.001). CONCLUSION: Alginate-hydrogel in addition to standard medical therapy for patients with advanced chronic HF was more effective than standard medical therapy alone for improving exercise capacity and symptoms. The results of AUGMENT-HF provide proof of concept for a pivotal trial. TRIAL REGISTRATION NUMBER: NCT01311791.

Published
2015

29. Reinstating Aberrant mTORC1 Activity in Huntington’s Disease Mice Improves Disease Phenotypes

Author

Lee, John H, Tecedor, Luis, Chen, Yong Hong, Monteys, Alex Mas, Sowada, Matthew J, Thompson, Leslie M, and Davidson, Beverly L

Subjects
Biological Psychology, Psychology, Orphan Drug, Neurosciences, Rare Diseases, Neurodegenerative, Brain Disorders, Huntington's Disease, Aetiology, 2.1 Biological and endogenous factors, Neurological, Animals, Atrophy, Disease Models, Animal, GTP-Binding Proteins, Humans, Huntington Disease, Lipogenesis, Mechanistic Target of Rapamycin Complex 1, Mice, Monomeric GTP-Binding Proteins, Multiprotein Complexes, Neostriatum, Neuropeptides, Phenotype, Ras Homolog Enriched in Brain Protein, Serotonin Plasma Membrane Transport Proteins, Signal Transduction, TOR Serine-Threonine Kinases, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

Huntington's disease (HD) is caused by a polyglutamine tract expansion in huntingtin (HTT). Despite HTTs ubiquitous expression, there is early and robust vulnerability in striatum, the cause of which is poorly understood. Here, we provide evidence that impaired striatal mTORC1 activity underlies varied metabolic and degenerative phenotypes in HD brain and show that introducing the constitutively active form of the mTORC1 regulator, Rheb, into HD mouse brain, alleviates mitochondrial dysfunction, aberrant cholesterol homeostasis, striatal atrophy, impaired dopamine signaling, and increases autophagy. We also find that the expression of Rhes, a striatum-enriched mTOR activator, is reduced in HD patient and mouse brain and that exogenous addition of Rhes alleviates motor deficits and improves brain pathology in HD mice. Our combined work indicates that impaired Rhes/mTORC1 activity in HD brain may underlie the notable striatal susceptibility and thus presents a promising therapeutic target for HD therapy.

Published
2015

30. Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity

Author

Mark K. Bakker, Jos P. Kanning, Gad Abraham, Amy E. Martinsen, Bendik S. Winsvold, John-Anker Zwart, Romain Bourcier, Tomonobu Sawada, Masaru Koido, Yoichiro Kamatani, Sandrine Morel, Philippe Amouyel, Stéphanie Debette, Philippe Bijlenga, Takiy Berrandou, Santhi K. Ganesh, Nabila Bouatia-Naji, Gregory Jones, Matthew Bown, Gabriel J.E. Rinkel, Jan H. Veldink, Ynte M. Ruigrok, Anne Hege Aamodt, Anne Heidi Skogholt, Ben M Brumpton, Cristen J Willer, Else C Sandset, Espen S Kristoffersen, Hanne Ellekjær, Ingrid Heuch, Jonas B Nielsen, Knut Hagen, Kristian Hveem, Lars G Fritsche, Laurent F Thomas, Linda M Pedersen, Maiken E Gabrielsen, Oddgeir L Holmen, Sigrid Børte, Wei Zhou, Shérine Abboud, Massimo Pandolfo, Vincent Thijs, Didier Leys, Marie Bodenant, Fabien Louillet, Emmanuel Touzé, Jean-Louis Mas, Yves Samson, Sara Leder, Anne Léger, Sandrine Deltour, Sophie Crozier, Isabelle Méresse, Sandrine Canaple, Olivier Godefroy, Maurice Giroud, Yannick Béjot, Pierre Decavel, Elizabeth Medeiros, Paola Montiel, Thierry Moulin, Fabrice Vuillier, Jean Dallongeville, Antti J Metso, Tiina Metso, Turgut Tatlisumak, Caspar Grond-Ginsbach, Christoph Lichy, Manja Kloss, Inge Werner, Marie-Luise Arnold, Michael Dos Santos, Armin Grau, Martin Dichgans, Constanze Thomas-Feles, Ralf Weber, Tobias Brandt, Alessandro Pezzini, Valeria De Giuli, Filomena Caria, Loris Poli, Alessandro Padovani, Anna Bersano, Silvia Lanfranconi, Simone Beretta, Carlo Ferrarese, Giacomo Giacolone, Stefano Paolucci, Philippe Lyrer, Stefan Engelter, Felix Fluri, Florian Hatz, Dominique Gisler, Leo Bonati, Henrik Gensicke, Margareth Amort, Hugh Markus, Jennifer Majersik, Bradford Worrall, Andrew Southerland, John Cole, Steven Kittner, Evangelos Evangelou, Helen R Warren, He Gao, Georgios Ntritsos, Niki Dimou, Tonu Esko, Reedik Mägi, Lili Milani, Peter Almgren, Thibaud Boutin, Jun Ding, Franco Giulianini, Elizabeth G Holliday, Anne U Jackson, Ruifang Li-Gao, Wei-Yu Lin, Jian’an Luan, Massimo Mangino, Christopher Oldmeadow, Bram Peter Prins, Yong Qian, Muralidharan Sargurupremraj, Nabi Shah, Praveen Surendran, Sébastien Thériault, Niek Verweij, Sara M Willems, Jing-Hua Zhao, John Connell, Renée de Mutsert, Alex SF Doney, Martin Farrall, Cristina Menni, Andrew D Morris, Raymond Noordam, Guillaume Paré, Neil R Poulter, Denis C Shields, Alice Stanton, Simon Thom, Gonçalo Abecasis, Najaf Amin, Dan E Arking, Kristin L Ayers, Caterina M Barbieri, Chiara Batini, Joshua C Bis, Tineka Blake, Murielle Bochud, Michael Boehnke, Eric Boerwinkle, Dorret I Boomsma, Erwin P Bottinger, Peter S Braund, Marco Brumat, Archie Campbell, Harry Campbell, Aravinda Chakravarti, John C Chambers, Ganesh Chauhan, Marina Ciullo, Massimiliano Cocca, Francis Collins, Heather J Cordell, Gail Davies, Martin H de Borst, Eco J de Geus, Ian J Deary, Joris Deelen, Fabiola Del Greco M, Cumhur Yusuf Demirkale, Marcus Dörr, Georg B Ehret, Roberto Elosua, Stefan Enroth, A Mesut Erzurumluoglu, Teresa Ferreira, Mattias Frånberg, Oscar H Franco, Ilaria Gandin, Paolo Gasparini, Vilmantas Giedraitis, Christian Gieger, Giorgia Girotto, Anuj Goel, Alan J Gow, Vilmundur Gudnason, Xiuqing Guo, Ulf Gyllensten, Anders Hamsten, Tamara B Harris, Sarah E Harris, Catharina A Hartman, Aki S Havulinna, Andrew A Hicks, Edith Hofer, Albert Hofman, Jouke-Jan Hottenga, Jennifer E Huffman, Shih-Jen Hwang, Erik Ingelsson, Alan James, Rick Jansen, Marjo-Riitta Jarvelin, Roby Joehanes, Åsa Johansson, Andrew D Johnson, Peter K Joshi, Pekka Jousilahti, J Wouter Jukema, Antti Jula, Mika Kähönen, Sekar Kathiresan, Bernard D Keavney, Kay-Tee Khaw, Paul Knekt, Joanne Knight, Ivana Kolcic, Jaspal S Kooner, Seppo Koskinen, Kati Kristiansson, Zoltan Kutalik, Maris Laan, Marty Larson, Lenore J Launer, Benjamin Lehne, Terho Lehtimäki, David CM Liewald, Li Lin, Lars Lind, Cecilia M Lindgren, YongMei Liu, Ruth JF Loos, Lorna M Lopez, Yingchang Lu, Leo-Pekka Lyytikäinen, Anubha Mahajan, Chrysovalanto Mamasoula, Jaume Marrugat, Jonathan Marten, Yuri Milaneschi, Anna Morgan, Andrew P Morris, Alanna C Morrison, Peter J Munson, Mike A Nalls, Priyanka Nandakumar, Christopher P Nelson, Teemu Niiranen, Ilja M Nolte, Teresa Nutile, Albertine J Oldehinkel, Ben A Oostra, Paul F O’Reilly, Elin Org, Sandosh Padmanabhan, Walter Palmas, Aarno Palotie, Alison Pattie, Brenda WJH Penninx, Markus Perola, Annette Peters, Ozren Polasek, Peter P Pramstaller, Quang Tri Nguyen, Olli T Raitakari, Rainer Rettig, Kenneth Rice, Paul M Ridker, Janina S Ried, Harriëtte Riese, Samuli Ripatti, Antonietta Robino, Lynda M Rose, Jerome I Rotter, Igor Rudan, Daniela Ruggiero, Yasaman Saba, Cinzia F Sala, Veikko Salomaa, Nilesh J Samani, Antti-Pekka Sarin, Reinhold Schmidt, Helena Schmidt, Nick Shrine, David Siscovick, Albert V Smith, Harold Snieder, Siim Sõber, Rossella Sorice, John M Starr, David J Stott, David P Strachan, Rona J Strawbridge, Johan Sundström, Morris A Swertz, Kent D Taylor, Alexander Teumer, Martin D Tobin, Maciej Tomaszewski, Daniela Toniolo, Michela Traglia, Stella Trompet, Jaakko Tuomilehto, Christophe Tzourio, André G Uitterlinden, Ahmad Vaez, Peter J van der Most, Cornelia M van Duijn, Germaine C Verwoert, Veronique Vitart, Uwe Völker, Peter Vollenweider, Dragana Vuckovic, Hugh Watkins, Sarah H Wild, Gonneke Willemsen, James F Wilson, Alan F Wright, Jie Yao, Tatijana Zemunik, Weihua Zhang, John R Attia, Adam S Butterworth, Daniel I Chasman, David Conen, Francesco Cucca, John Danesh, Caroline Hayward, Joanna MM Howson, Markku Laakso, Edward G Lakatta, Claudia Langenberg, Olle Melander, Dennis O Mook-Kanamori, Colin NA Palmer, Lorenz Risch, Robert A Scott, Rodney J Scott, Peter Sever, Tim D Spector, Pim van der Harst, Nicholas J Wareham, Eleftheria Zeggini, Daniel Levy, Patricia B Munroe, Christopher Newton-Cheh, Morris J Brown, Andres Metspalu, Bruce M. Psaty, Louise V Wain, Paul Elliott, Mark J Caulfield, Padhraig Gormley, Verneri Anttila, Priit Palta, Tune H Pers, Kai-How Farh, Ester Cuenca-Leon, Mikko Muona, Nicholas A Furlotte, Tobias Kurth, Andres Ingason, George McMahon, Lannie Ligthart, Gisela M Terwindt, Mikko Kallela, Tobias M Freilinger, Caroline Ran, Scott G Gordon, Anine H Stam, Stacy Steinberg, Guntram Borck, Markku Koiranen, Lydia Quaye, Hieab H H Adams, Juho Wedenoja, David A Hinds, Julie E Buring, Markus Schürks, Maria Gudlaug Hrafnsdottir, Hreinn Stefansson, Susan M Ring, Brenda W J H Penninx, Markus Färkkilä, Ville Artto, Mari Kaunisto, Salli Vepsäläinen, Rainer Malik, Andrew C Heath, Pamela A F Madden, Nicholas G Martin, Grant W Montgomery, Mitja I Kurki, Mart Kals, Kalle Pärn, Eija Hämäläinen, Hailiang Huang, Andrea E Byrnes, Lude Franke, Jie Huang, Evie Stergiakouli, Phil H Lee, Cynthia Sandor, Caleb Webber, Zameel Cader, Bertram Muller-Myhsok, Stefan Schreiber, Thomas Meitinger, Johan G Eriksson, Kauko Heikkilä, Elizabeth Loehrer, Andre G Uitterlinden, Lynn Cherkas, Audun Stubhaug, Christopher S Nielsen, Minna Männikkö, Evelin Mihailov, Hartmut Göbel, Ann-Louise Esserlind, Anne Francke Christensen, Thomas Folkmann Hansen, Thomas Werge, Jaakko Kaprio, Arpo J Aromaa, Olli Raitakari, M Arfan Ikram, Tim Spector, Marjo-Riitta Järvelin, Christian Kubisch, Michel D Ferrari, Andrea C Belin, Maija Wessman, Arn M J M van den Maagdenberg, George Davey Smith, Kari Stefansson, Nicholas Eriksson, Mark J Daly, Benjamin M Neale, Jes Olesen, Dale R Nyholt, Masato Akiyama, Varinder S. Alg, Joseph P. Broderick, Ben M. Brumpton, Jérôme Dauvillier, Hubert Desal, Christian Dina, Christoph M. Friedrich, Emília I. Gaál-Paavola, Jean-Christophe Gentric, Sven Hirsch, Isabel C. Hostettler, Henry Houlden, Juha E. Jääskeläinen, Marianne Bakke Johnsen, Liming Li, Kuang Lin, Antti Lindgren, Olivier Martin, Koichi Matsuda, Iona Y. Millwood, Olivier Naggara, Mika Niemelä, Joanna Pera, Richard Redon, Guy A. Rouleau, Marie Søfteland Sandvei, Sabine Schilling, Eimad Shotar, Agnieszka Slowik, Chikashi Terao, W. M. Monique Verschuren, Robin G. Walters, David J. Werring, Cristen J. Willer, Daniel Woo, Bradford B. Worrall, Sirui Zhou, Biological Psychology, Amsterdam Reproduction & Development, APH - Mental Health, APH - Methodology, AMS - Sports, AMS - Ageing & Vitality, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Systems Ecology, Sociology and Social Gerontology, Bakker, Mark K., Kanning, Jos P., Abraham, Gad, Martinsen, Amy E., Winsvold, Bendik S., Zwart, John-Anker, Bourcier, Romain, Sawada, Tomonobu, Koido, Masaru, Kamatani, Yoichiro, Morel, Sandrine, Amouyel, Philippe, Debette, Stéphanie, Bijlenga, Philippe, Berrandou, Takiy, Ganesh, Santhi K., Bouatia-Naji, Nabila, Jones, Gregory, Bown, Matthew, Rinkel, Gabriel J. E., Veldink, Jan H., Ruigrok, Ynte M., Girotto, G., All-In Stroke, Hunt, Group, Cadisp, Consortium for Blood Pressure, International, Headache Genetics Consortium, International, Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group, International, Utrecht University [Utrecht], Baker Heart and Diabetes Institute (AUSTRALIA), University of Melbourne, University of Oslo (UiO), Norwegian University of Science and Technology (NTNU), Oslo University Hospital [Oslo], Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), The University of Tokyo (UTokyo), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Université de Genève = University of Geneva (UNIGE), Excellence Laboratory LabEx DISTALZ, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University of Michigan Medical School [Ann Arbor], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, University of Otago [Dunedin, Nouvelle-Zélande], University of Leicester, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), CHU Amiens-Picardie, HUNT All-In Stroke, CADISP group, International Consortium for Blood Pressure, International Headache Genetics Consortium, International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group: Anne Hege Aamodt, Anne Heidi Skogholt, Ben M Brumpton, Cristen J Willer, Else C Sandset, Espen S Kristoffersen, Hanne Ellekjær, Ingrid Heuch, Jonas B Nielsen, Knut Hagen, Kristian Hveem, Lars G Fritsche, Laurent F Thomas, Linda M Pedersen, Maiken E Gabrielsen, Oddgeir L Holmen, Sigrid Børte, Wei Zhou, Shérine Abboud, Massimo Pandolfo, Vincent Thijs, Didier Leys, Marie Bodenant, Fabien Louillet, Emmanuel Touzé, Jean-Louis Mas, Yves Samson, Sara Leder, Anne Léger, Sandrine Deltour, Sophie Crozier, Isabelle Méresse, Sandrine Canaple, Olivier Godefroy, Maurice Giroud, Yannick Béjot, Pierre Decavel, Elizabeth Medeiros, Paola Montiel, Thierry Moulin, Fabrice Vuillier, Jean Dallongeville, Antti J Metso, Tiina Metso, Turgut Tatlisumak, Caspar Grond-Ginsbach, Christoph Lichy, Manja Kloss, Inge Werner, Marie-Luise Arnold, Michael Dos Santos, Armin Grau, Martin Dichgans, Constanze Thomas-Feles, Ralf Weber, Tobias Brandt, Alessandro Pezzini, Valeria De Giuli, Filomena Caria, Loris Poli, Alessandro Padovani, Anna Bersano, Silvia Lanfranconi, Simone Beretta, Carlo Ferrarese, Giacomo Giacolone, Stefano Paolucci, Philippe Lyrer, Stefan Engelter, Felix Fluri, Florian Hatz, Dominique Gisler, Leo Bonati, Henrik Gensicke, Margareth Amort, Hugh Markus, Jennifer Majersik, Bradford Worrall, Andrew Southerland, John Cole, Steven Kittner, Evangelos Evangelou, Helen R Warren, He Gao, Georgios Ntritsos, Niki Dimou, Tonu Esko, Reedik Mägi, Lili Milani, Peter Almgren, Thibaud Boutin, Jun Ding, Franco Giulianini, Elizabeth G Holliday, Anne U Jackson, Ruifang Li-Gao, Wei-Yu Lin, Jian'an Luan, Massimo Mangino, Christopher Oldmeadow, Bram Peter Prins, Yong Qian, Muralidharan Sargurupremraj, Nabi Shah, Praveen Surendran, Sébastien Thériault, Niek Verweij, Sara M Willems, Jing-Hua Zhao, John Connell, Renée de Mutsert, Alex Sf Doney, Martin Farrall, Cristina Menni, Andrew D Morris, Raymond Noordam, Guillaume Paré, Neil R Poulter, Denis C Shields, Alice Stanton, Simon Thom, Gonçalo Abecasis, Najaf Amin, Dan E Arking, Kristin L Ayers, Caterina M Barbieri, Chiara Batini, Joshua C Bis, Tineka Blake, Murielle Bochud, Michael Boehnke, Eric Boerwinkle, Dorret I Boomsma, Erwin P Bottinger, Peter S Braund, Marco Brumat, Archie Campbell, Harry Campbell, Aravinda Chakravarti, John C Chambers, Ganesh Chauhan, Marina Ciullo, Massimiliano Cocca, Francis Collins, Heather J Cordell, Gail Davies, Martin H de Borst, Eco J de Geus, Ian J Deary, Joris Deelen, Fabiola Del Greco M, Cumhur Yusuf Demirkale, Marcus Dörr, Georg B Ehret, Roberto Elosua, Stefan Enroth, A Mesut Erzurumluoglu, Teresa Ferreira, Mattias Frånberg, Oscar H Franco, Ilaria Gandin, Paolo Gasparini, Vilmantas Giedraitis, Christian Gieger, Giorgia Girotto, Anuj Goel, Alan J Gow, Vilmundur Gudnason, Xiuqing Guo, Ulf Gyllensten, Anders Hamsten, Tamara B Harris, Sarah E Harris, Catharina A Hartman, Aki S Havulinna, Andrew A Hicks, Edith Hofer, Albert Hofman, Jouke-Jan Hottenga, Jennifer E Huffman, Shih-Jen Hwang, Erik Ingelsson, Alan James, Rick Jansen, Marjo-Riitta Jarvelin, Roby Joehanes, Åsa Johansson, Andrew D Johnson, Peter K Joshi, Pekka Jousilahti, J Wouter Jukema, Antti Jula, Mika Kähönen, Sekar Kathiresan, Bernard D Keavney, Kay-Tee Khaw, Paul Knekt, Joanne Knight, Ivana Kolcic, Jaspal S Kooner, Seppo Koskinen, Kati Kristiansson, Zoltan Kutalik, Maris Laan, Marty Larson, Lenore J Launer, Benjamin Lehne, Terho Lehtimäki, David Cm Liewald, Li Lin, Lars Lind, Cecilia M Lindgren, YongMei Liu, Ruth Jf Loos, Lorna M Lopez, Yingchang Lu, Leo-Pekka Lyytikäinen, Anubha Mahajan, Chrysovalanto Mamasoula, Jaume Marrugat, Jonathan Marten, Yuri Milaneschi, Anna Morgan, Andrew P Morris, Alanna C Morrison, Peter J Munson, Mike A Nalls, Priyanka Nandakumar, Christopher P Nelson, Teemu Niiranen, Ilja M Nolte, Teresa Nutile, Albertine J Oldehinkel, Ben A Oostra, Paul F O'Reilly, Elin Org, Sandosh Padmanabhan, Walter Palmas, Aarno Palotie, Alison Pattie, Brenda Wjh Penninx, Markus Perola, Annette Peters, Ozren Polasek, Peter P Pramstaller, Quang Tri Nguyen, Olli T Raitakari, Rainer Rettig, Kenneth Rice, Paul M Ridker, Janina S Ried, Harriëtte Riese, Samuli Ripatti, Antonietta Robino, Lynda M Rose, Jerome I Rotter, Igor Rudan, Daniela Ruggiero, Yasaman Saba, Cinzia F Sala, Veikko Salomaa, Nilesh J Samani, Antti-Pekka Sarin, Reinhold Schmidt, Helena Schmidt, Nick Shrine, David Siscovick, Albert V Smith, Harold Snieder, Siim Sõber, Rossella Sorice, John M Starr, David J Stott, David P Strachan, Rona J Strawbridge, Johan Sundström, Morris A Swertz, Kent D Taylor, Alexander Teumer, Martin D Tobin, Maciej Tomaszewski, Daniela Toniolo, Michela Traglia, Stella Trompet, Jaakko Tuomilehto, Christophe Tzourio, André G Uitterlinden, Ahmad Vaez, Peter J van der Most, Cornelia M van Duijn, Germaine C Verwoert, Veronique Vitart, Uwe Völker, Peter Vollenweider, Dragana Vuckovic, Hugh Watkins, Sarah H Wild, Gonneke Willemsen, James F Wilson, Alan F Wright, Jie Yao, Tatijana Zemunik, Weihua Zhang, John R Attia, Adam S Butterworth, Daniel I Chasman, David Conen, Francesco Cucca, John Danesh, Caroline Hayward, Joanna Mm Howson, Markku Laakso, Edward G Lakatta, Claudia Langenberg, Olle Melander, Dennis O Mook-Kanamori, Colin Na Palmer, Lorenz Risch, Robert A Scott, Rodney J Scott, Peter Sever, Tim D Spector, Pim van der Harst, Nicholas J Wareham, Eleftheria Zeggini, Daniel Levy, Patricia B Munroe, Christopher Newton-Cheh, Morris J Brown, Andres Metspalu, Bruce M Psaty, Louise V Wain, Paul Elliott, Mark J Caulfield, Padhraig Gormley, Verneri Anttila, Priit Palta, Tonu Esko, Tune H Pers, Kai-How Farh, Ester Cuenca-Leon, Mikko Muona, Nicholas A Furlotte, Tobias Kurth, Andres Ingason, George McMahon, Lannie Ligthart, Gisela M Terwindt, Mikko Kallela, Tobias M Freilinger, Caroline Ran, Scott G Gordon, Anine H Stam, Stacy Steinberg, Guntram Borck, Markku Koiranen, Lydia Quaye, Hieab H H Adams, Terho Lehtimäki, Antti-Pekka Sarin, Juho Wedenoja, David A Hinds, Julie E Buring, Markus Schürks, Paul M Ridker, Maria Gudlaug Hrafnsdottir, Hreinn Stefansson, Susan M Ring, Jouke-Jan Hottenga, Brenda W J H Penninx, Markus Färkkilä, Ville Artto, Mari Kaunisto, Salli Vepsäläinen, Rainer Malik, Andrew C Heath, Pamela A F Madden, Nicholas G Martin, Grant W Montgomery, Mitja I Kurki, Mart Kals, Reedik Mägi, Kalle Pärn, Eija Hämäläinen, Hailiang Huang, Andrea E Byrnes, Lude Franke, Jie Huang, Evie Stergiakouli, Phil H Lee, Cynthia Sandor, Caleb Webber, Zameel Cader, Bertram Muller-Myhsok, Stefan Schreiber, Thomas Meitinger, Johan G Eriksson, Veikko Salomaa, Kauko Heikkilä, Elizabeth Loehrer, Andre G Uitterlinden, Albert Hofman, Cornelia M van Duijn, Lynn Cherkas, Linda M Pedersen, Audun Stubhaug, Christopher S Nielsen, Minna Männikkö, Evelin Mihailov, Lili Milani, Hartmut Göbel, Ann-Louise Esserlind, Anne Francke Christensen, Thomas Folkmann Hansen, Thomas Werge, Jaakko Kaprio, Arpo J Aromaa, Olli Raitakari, M Arfan Ikram, Tim Spector, Marjo-Riitta Järvelin, Andres Metspalu, Christian Kubisch, David P Strachan, Michel D Ferrari, Andrea C Belin, Martin Dichgans, Maija Wessman, Arn M J M van den Maagdenberg, Dorret I Boomsma, George Davey Smith, Kari Stefansson, Nicholas Eriksson, Mark J Daly, Benjamin M Neale, Jes Olesen, Daniel I Chasman, Dale R Nyholt, Aarno Palotie, Masato Akiyama, Varinder S Alg, Sigrid Børte, Joseph P Broderick, Ben M Brumpton, Jérôme Dauvillier, Hubert Desal, Christian Dina, Christoph M Friedrich, Emília I Gaál-Paavola, Jean-Christophe Gentric, Sven Hirsch, Isabel C Hostettler, Henry Houlden, Kristian Hveem, Juha E Jääskeläinen, Marianne Bakke Johnsen, Liming Li, Kuang Lin, Antti Lindgren, Olivier Martin, Koichi Matsuda, Iona Y Millwood, Olivier Naggara, Mika Niemelä, Joanna Pera, Richard Redon, Guy A Rouleau, Marie Søfteland Sandvei, Sabine Schilling, Eimad Shotar, Agnieszka Slowik, Chikashi Terao, W M Monique Verschuren, Robin G Walters, David J Werring, Cristen J Willer, Daniel Woo, Bradford B Worrall, Sirui Zhou, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, and Admin, Oskar

Subjects
Advanced and Specialized Nursing, Incidence, risk assessment, Smoking/epidemiology, intracranial aneurysm, genetic heterogeneity, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Risk Factors, Intracranial Aneurysm/epidemiology, Humans, Subarachnoid Hemorrhage/epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, genetics, Neurology (clinical), aneurysmal subarachnoid hemorrhage, genetic, Cardiology and Cardiovascular Medicine
Abstract

Background: Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined set of unruptured IA and ASAH) and (2) assess its association with patient characteristics. Methods: A genetic risk score incorporating genetic association data for IA and 17 traits related to IA (so-called metaGRS) was created using 1161 IA cases and 407 392 controls from the UK Biobank population study. The metaGRS was validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68 568 controls from the Nordic HUNT population study. Furthermore, we assessed association between the metaGRS and patient characteristics in a cohort of 5560 IA patients. Results: Per SD increase of metaGRS, the hazard ratio for ASAH incidence was 1.34 (95% CI, 1.20–1.51) and the odds ratio for IA presence 1.09 (95% CI, 1.01–1.18). Upon including the metaGRS on top of clinical risk factors, the concordance index to predict ASAH hazard increased from 0.63 (95% CI, 0.59–0.67) to 0.65 (95% CI, 0.62–0.69), while prediction of IA presence did not improve. The metaGRS was statistically significantly associated with age at ASAH (β=−4.82×10 −3 per year [95% CI, −6.49×10 −3 to −3.14×10 −3 ]; P =1.82×10 −8 ), and location of IA at the internal carotid artery (odds ratio=0.92 [95% CI, 0.86–0.98]; P =0.0041). Conclusions: The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic prediction studies of IA and ASAH.

Published
2023

31. Associations of medication with subcortical morphology across the lifespan in OCD: Results from the international ENIGMA Consortium

Author

Iliyan Ivanov, Premika S.W. Boedhoe, Yoshinari Abe, Pino Alonso, Stephanie H. Ameis, Paul D. Arnold, Srinivas Balachander, Justin T. Baker, Nerisa Banaj, Nuria Bargalló, Marcelo C. Batistuzzo, Francesco Benedetti, Jan C. Beucke, Irene Bollettini, Silvia Brem, Brian P. Brennan, Jan Buitelaar, Rosa Calvo, Yuqi Cheng, Kang Ik K. Cho, Sara Dallaspezia, Damiaan Denys, Juliana B. Diniz, Benjamin A. Ely, Jamie D. Feusner, Sónia Ferreira, Kate D. Fitzgerald, Martine Fontaine, Patricia Gruner, Gregory L. Hanna, Yoshiyuki Hirano, Marcelo Q. Hoexter, Chaim Huyser, Keisuke Ikari, Anthony James, Fern Jaspers-Fayer, Hongyan Jiang, Norbert Kathmann, Christian Kaufmann, Minah Kim, Kathrin Koch, Jun Soo Kwon, Luisa Lázaro, Yanni Liu, Christine Lochner, Rachel Marsh, Ignacio Martínez-Zalacaín, David Mataix-Cols, José M. Menchón, Luciano Minuzzi, Astrid Morer, Pedro Morgado, Akiko Nakagawa, Takashi Nakamae, Tomohiro Nakao, Janardhanan C. Narayanaswamy, Erika L. Nurmi, Sanghoon Oh, Chris Perriello, John C. Piacentini, Maria Picó-Pérez, Fabrizio Piras, Federica Piras, Y.C. Janardhan Reddy, Daniela Rodriguez Manrique, Yuki Sakai, Eiji Shimizu, H. Blair Simpson, Noam Soreni, Carles Soriano-Mas, Gianfranco Spalletta, Emily R. Stern, Michael C. Stevens, S. Evelyn Stewart, Philip R. Szeszko, David F. Tolin, Daan van Rooij, Dick J. Veltman, Ysbrand D. van der Werf, Guido A. van Wingen, Ganesan Venkatasubramanian, Susanne Walitza, Zhen Wang, Anri Watanabe, Lidewij H. Wolters, Xiufeng Xu, Je-Yeon Yun, Mojtaba Zarei, Fengrui Zhang, Qing Zhao, Neda Jahanshad, Sophia I. Thomopoulos, Paul M. Thompson, Dan J. Stein, Odile A. van den Heuvel, Joseph O'Neill, Sara Poletti, Egill Axfjord Fridgeirsson, Toshikazu Ikuta, Stella J. de Wit, Chris Vriend, Selina Kasprzak, Masaru Kuno, Jumpei Takahashi, Euripedes C. Miguel, Roseli G. Shavitt, Morgan Hough, Jose C. Pariente, Ana E. Ortiz, Sara Bertolín, Eva Real, Cinto Segalàs, Pedro Silva Moreira, Nuno Sousa, Jin Narumoto, Kei Yamada, Jinsong Tang, Jean-Paul Fouche, Taekwan Kim, Sunah Choi, Minji Ha, Sunghyun Park, Anatomy and neurosciences, Psychiatry, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Neuroscience - Systems & Network Neuroscience, Amsterdam Neuroscience - Neurodegeneration, Adult Psychiatry, Child Psychiatry, Paediatric Psychosocial Care, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Graduate School, Ivanov, Iliyan, Boedhoe, Premika S W, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H, Arnold, Paul D, Balachander, Sriniva, Baker, Justin T, Banaj, Nerisa, Bargalló, Nuria, Batistuzzo, Marcelo C, Benedetti, Francesco, Beucke, Jan C, Bollettini, Irene, Brem, Silvia, Brennan, Brian P, Buitelaar, Jan, Calvo, Rosa, Cheng, Yuqi, Cho, Kang Ik K, Dallaspezia, Sara, Denys, Damiaan, Diniz, Juliana B, Ely, Benjamin A, Feusner, Jamie D, Ferreira, Sónia, Fitzgerald, Kate D, Fontaine, Martine, Gruner, Patricia, Hanna, Gregory L, Hirano, Yoshiyuki, Hoexter, Marcelo Q, Huyser, Chaim, Ikari, Keisuke, James, Anthony, Jaspers-Fayer, Fern, Jiang, Hongyan, Kathmann, Norbert, Kaufmann, Christian, Kim, Minah, Koch, Kathrin, Kwon, Jun Soo, Lázaro, Luisa, Liu, Yanni, Lochner, Christine, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Menchón, José M, Minuzzi, Luciano, Morer, Astrid, Morgado, Pedro, Nakagawa, Akiko, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C, Nurmi, Erika L, Oh, Sanghoon, Perriello, Chri, Piacentini, John C, Picó-Pérez, Maria, Piras, Fabrizio, Piras, Federica, Reddy, Y C Janardhan, Manrique, Daniela Rodriguez, Sakai, Yuki, Shimizu, Eiji, Simpson, H Blair, Soreni, Noam, Soriano-Mas, Carle, Spalletta, Gianfranco, Stern, Emily R, Stevens, Michael C, Stewart, S Evelyn, Szeszko, Philip R, Tolin, David F, van Rooij, Daan, Veltman, Dick J, van der Werf, Ysbrand D, van Wingen, Guido A, Venkatasubramanian, Ganesan, Walitza, Susanne, Wang, Zhen, Watanabe, Anri, Wolters, Lidewij H, Xu, Xiufeng, Yun, Je-Yeon, Zarei, Mojtaba, Zhang, Fengrui, Zhao, Qing, Jahanshad, Neda, Thomopoulos, Sophia I, Thompson, Paul M, Stein, Dan J, van den Heuvel, Odile A, and O'Neill, Joseph

Subjects
Obsessive-Compulsive Disorder, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], OCD, Psychotropics, Longevity, SRIs, Magnetic Resonance Imaging, Benzodiazepines, Psychiatry and Mental health, Clinical Psychology, Age, Cross-Sectional Studies, Subcortical volumes, 130 000 Cognitive Neurology & Memory, Child, Preschool, Serotonin Uptake Inhibitors, Humans, Child, Selective Serotonin Reuptake Inhibitors, Aged, Antipsychotic Agents
Abstract

Background: Widely used psychotropic medications for obsessive-compulsive disorder (OCD) may change the volumes of subcortical brain structures, and differently in children vs. adults. We measured subcortical volumes cross-sectionally in patients finely stratified for age taking various common classes of OCD drugs. Methods: The ENIGMA-OCD consortium sample (1081 medicated/1159 unmedicated OCD patients and 2057 healthy controls aged 6–65) was divided into six successive 6–10-year age-groups. Individual structural MRIs were parcellated automatically using FreeSurfer into 8 regions-of-interest (ROIs). ROI volumes were compared between unmedicated and medicated patients and controls, and between patients taking serotonin reuptake inhibitors (SRIs), tricyclics (TCs), antipsychotics (APs), or benzodiazepines (BZs) and unmedicated patients. Results: Compared to unmedicated patients, volumes of accumbens, caudate, and/or putamen were lower in children aged 6–13 and adults aged 50–65 with OCD taking SRIs (Cohen's d = −0.24 to −0.74). Volumes of putamen, pallidum (d = 0.18–0.40), and ventricles (d = 0.31–0.66) were greater in patients aged 20–29 receiving APs. Hippocampal volumes were smaller in patients aged 20 and older taking TCs and/or BZs (d = −0.27 to −1.31). Conclusions: Results suggest that TCs and BZs could potentially aggravate hippocampal atrophy of normal aging in older adults with OCD, whereas SRIs may reduce striatal volumes in young children and older adults. Similar to patients with psychotic disorders, OCD patients aged 20–29 may experience subcortical nuclear and ventricular hypertrophy in relation to APs. Although cross-sectional, present results suggest that commonly prescribed agents exert macroscopic effects on subcortical nuclei of unknown relation to therapeutic response.

Published
2022

32. Reduction in Early Stroke Risk in Carotid Stenosis With Transient Ischemic Attack Associated With Statin Treatment

Author

Merwick, Áine, Albers, Gregory W, Arsava, Ethem M, Ay, Hakan, Calvet, David, Coutts, Shelagh B, Cucchiara, Brett L, Demchuk, Andrew M, Giles, Matthew F, Mas, Jean-Louis, Olivot, Jean Marc, Purroy, Francisco, Rothwell, Peter M, Saver, Jeffrey L, Sharma, Vijay K, Tsivgoulis, Georgios, and Kelly, Peter J

Subjects
Cardiovascular, Atherosclerosis, Clinical Research, Brain Disorders, Stroke, Prevention, Neurosciences, Aged, Aged, 80 and over, Brain Ischemia, Carotid Stenosis, Diffusion Magnetic Resonance Imaging, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Male, Middle Aged, Radiography, Risk Factors, Time Factors, carotid stenosis, ischemic attack, transient, statin, ischemic attack, transient, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Neurology & Neurosurgery
Abstract

Background and purposeStatins reduce stroke risk when initiated months after transient ischemic attack (TIA)/stroke and reduce early vascular events in acute coronary syndromes, possibly via pleiotropic plaque stabilization. Few data exist on acute statin use in TIA. We aimed to determine whether statin pretreatment at TIA onset modified early stroke risk in carotid stenosis.MethodsWe analyzed data from 2770 patients with TIA from 11 centers, 387 with ipsilateral carotid stenosis. ABCD2 score, abnormal diffusion weighted imaging, medication pretreatment, and early stroke were recorded.ResultsIn patients with carotid stenosis, 7-day stroke risk was 8.3% (95% confidence interval [CI], 5.7-11.1) compared with 2.7% (CI, 2.0%-3.4%) without stenosis (P

Published
2013

33. Impact of the HAS 2019 French guidelines on the frequency of hospital undernutrition in children

Author

Margaux Richou, Olivier L. Mantha, Noël Peretti, Béatrice Dubern, Emmanuel Mas, Régis Hankard, and Arnaud De Luca

Subjects
Hospitalization, Nutrition Assessment, Nutritional Support, Malnutrition, Pediatrics, Perinatology and Child Health, Humans, Nutritional Status, Child, Hospitals
Abstract

In 2019, the French National Authority for Health (Haute Autorité de Santé, HAS) published guidelines on the diagnosis of undernutrition. The present article focuses on the impact of switching from the 2012 guidelines of the Nutrition Committee of the French Paediatric Society (CNSFP) to the HAS guidelines on the frequency of hospital undernutrition in children. We selected for the period 2010-2019 from the ePINUT database: (1) all children aged more than 2 years with (2) clinically confirmed nutritional status in (3) French sites. The frequency of undernutrition was 15.4% vs. 28.8% using the CNSFP and HAS criteria, respectively (p 0.01; n = 6304). When compared to non-malnourished children regardless of the criteria used, malnourished children: (1) stayed longer in hospital (CNSFP: 9.0 ± 11.8 vs. 6.5 ± 8.7 days, p 0.01; HAS: 7.8 ± 10.1 vs. 6.4 ± 8.4 days, p 0.01), (2) gained more weight during hospitalization (% of weight at admission) (CNSFP: +1.4 ± 4.1 vs. -0.3 ± 3.5%, p 0.01; HAS: +2.3 ± 4.7 vs. -0.1 ± 3.4%, p 0.01), and (3) received nutritional support more frequently during hospitalization (CNSFP: 20% vs. 5%, p 0.01; HAS: 13% vs. 4%, p 0.01). Switching to the HAS guidelines resulted in an almost twofold higher frequency of undernutrition in hospitalized children. Initiation of nutritional care remained low considering the nutritional status. The present study warrants interventional studies to determine which children may benefit more from nutritional therapy to improve their outcome.

Published
2023

34. Workflows and Outcomes in Patients With Suspected Large Vessel Occlusion Stroke Triaged in Urban and Nonurban Areas

Author

Alvaro Garcia-Tornel, Monica Millan, Marta Rubiera, Alejandro Bustamante, Manuel Requena, Laura Dorado, Marta Olivé-Gadea, Xavier Jiménez, Angels Soto, Marisol Querol, Maria Hernández-Pérez, Meritxell Gomis, Pere Cardona, Xabier Urra, Francesc Purroy, Yolanda Silva, Xavier Ustrell, Patricia Esteve, Mercè Salvat-Plana, Miquel Gallofré, Carlos Molina, Antoni Dávalos, Tudor Jovin, Sonia Abilleira, Marc Ribo, Natalia Pérez de la Ossa, Marc Ribó Jacobi, Estela Sanjuan, Katherine Santana, Noelia Rodríguez, Jorge Pagola, David Rodriguez-Luna, Olga Maisterra, Estevo Santamarina, Marian Muchada, Jesús Juega, Sandra Boned, Antonio Palasi Franco, Álvaro García -Tornel, Matías Deck, Victoria Sala, Lucía Muñoz, Mónica Millán, Elena López-Cancio, María Hernández-Pérez, Jordi Ciurans, Daniela Samaniego, Tamara Canento, Lorena Martin, Anna Planas, Joaquin Broto, Agustín Sorrentino, Martí Paré, Nuole Zhu, Alicia Garrido, Laia Grau, Ane Miren Crespo, Silvia Presas, Miriam Almendrote, Alba Ramos, Giuseppe Lucente, Lourdes Ispierto, Manuel Lozano, Juan Luis Becerra, Marta Jiménez, Dolores Vilas Rolán, Nicolas Guanyabens, Josep Sanchez-Ojanguren, Alicia Martínez-Piñeiro, Sara Forcén, Mireia Gea, Marta Álvarez, Anna Ramos, Manuel Domínguez Lizarbe, Sara, Rubio Guerra, Irene Bragado, Andrea Arbex, Luis Rodríguez, Pere Cardona Portela, Helena Quesada García, Blanca Lara Rodríguez, Nuria Cayuela, Julia Miró, Clara Marzal, Andrés Paipa, Sergio Campoy, Ana Núñez, Pablo Arroyo, Sarah Besora, Vanessa Adell, Jaume Campdelacreu, Montse Alemany Martí, Belén González, Laura Bau Vila, Marta Fiter Crespo, Anna Berbel, Ma. Cristina Villaescusa Urbaneja, Núria Guillen, Nuria Vidal, Patricia Valentina Vérez Santamaria, Diego Herrero Navarro, Marta Simó, Mercedes Falip, Elisabeth Matas, Neus Mongay Ochoa, Ariadna Gifreu, Albert Muñoz, Lucía Romero, Eduard Portell, Guillermo Hernández Perez, F. Ruiz Esteve, Silvia Teixidor, Augusto Salazar Talavera, Roser Gómez, Xabier Urra Nuin, Martha Vargas, Ángel Chamorro, Sergio Amaro, Laura Llull, Arturo Renú, Salvatore Rudilosso, Raquel Sánchez del Valle, Helena Ariño, Nuria Solà, Delón la Puma, Francisco Gil, Juan Bernardo Gómez, Nuria Matos, Neus Falgàs, Sergi Borrego, Almudena Sánchez, Mircea Balasa, Carmen Montejo, Mar Guasp, David Reyes, Pablo Sánchez Cervilla, Jose Miguel Contador, Victor Augusto Vera Monge, Oscar Ramos, Alejandro Rodríguez, Ana Rodríguez Campello, Gemma Romeral Ballester, Mireia Llop Trujillano, Eva Giralt Steinhauer, Elisa Cuadrado Godia, Angel Javier Ois Santiago, Jordi Jimenez Conde, Joan Martí Fábregas, Daniel Guisado, Luís Prats, Pol Camps, Raquel Delgado, Alejandro Martínez Domeño, Rebeca Marín, David Cànovas, Jordi Estela, Marta Ros, Sonsoles Aranceta, Jordi Espinosa, Marta Rubio, Cristina Lafuente, Oriol Barrachina, Alicia Anguita, Anna Reverter, Carmen García, Gemma Sansa, Mariona Hervas, Monica Crosas, Tania Delgado, Jerzy Krupinski, Sonia Huertas Folch, Gemma Muñoz Gamito, Josep Trenado Alvarez, Teresa Subirana, Jessica Molina, Laura Comes Romero, Gemma Guardia Valls, Miriam Jover, Javier Joaquín Sotova, Sonia Mª García Sánchez, Sebastian Valenzuela (intensivista), Manuel Gómez-Choco, Juan José Mengual, M. Àngels Font, Mª Isabel Gómez Ruiz, Irati Zubizarreta, Susana Fernández González, Laura Gubieras, Carmen E. Cobos, Luis Mena Romo, Nuria Caballol, Luis Cano, Joaquín Serena Leal, Mikel Terceño Izarra, Irene Bragado Trigo, Saima Bashir Viturro, Laura Pardo Albiñana, Montserrat Reina Garrido, Carla Marco Cazcarra, Karol Enrique Uscamaita, Fabian Márquez, Cristina Coll, Mar Irida Lloret Villlas, Berta Solano Vila, Berta Alemany Perna, Daniel López Domínguezl, Mercedes de Lera, Anna Cots Foraster, Urszula Bojaryn, Ikram Benabdelhak, Gerard Mauri Capdevila, Jordi Sanahuja Montesinos, Daniel Vázquez, José Vicente Hervás, Cristina González, Alejandro Quílez, Mikel Vicente Pascual, María Ruiz, Yolanda Riba, M. Pilar Gil Villar, Cristina García, Xavier Ustrell Roig, Mònica Baldrich Mora, Anna Pellisé Guinjoan, Judit Borras, Alba Mañé Martínez, Rafael Marés, Jaume Viñas i Gaya, Laia Seró, Alan Flores, Paula Rodríguez, Gislaine Castilho, Angela Monterde Ortega, Silvia Reverté, Josep Zaragoza, Joan Josep Baiges, Gisela Martín Ozaeta, Sonia Escalante, Iago Payo, Júlia Saura Salvado, Natalia Mas Sala, Josep M Soler Insa, Ester Tio Vilamala, Josep Abos Navarro, Héctor Cruz Tabuenca, Tamara Canento Sánchez, Elisabet Roldán, Elsa Puiggrós Rubiol, Elisabet Franquet, Lidia Fuentes, Javier Donaire, Elena Martí, Laura Giménez, Junior Gil Vázquez, Eloisa Nieto Clara Gris Ambrós, Puri Rodríguez, José Félix Oletta, Pilar Pons Mellado, Catena, Bárbara Gómez, Vergilin Raileau, Esther Catena Ruíz, Oscar Pardina, Jordi Mercadal, María López-Diéguez, Pilar Pérez, Lourdes Gabarró, María Orriols, Joan Josep Canet, Mireia Roca, Muriel Álvaro, Francesc Boneu, Georgina Giménez, Jaume Albà, Francesc Gibert, Jéssica Garcia, Patricia Barragan, Gustavo Jurado, Josep Sabaté Ortega, Joan Amaurys Martínez Solano, Víctor Fernández, Mónica Torres, Ana Belén Montero Alvaredo, Laura Redondo Parejo, Josep Maria Aragonés, Anna Bullón, Cora Loste, Paula González, Neker Bejarano, Francisco Sanchez, Gianni Lucchetti, Xavier Pla, Javier Gimeno, Esteban Reynaga, Montse Barcons, Gabriel Celedón, Juan Ortiz, Goran Anastasovski, Oscar Mascaró, Javier Diez de los Ríos, Meritxell Feliu, Anna Ribera, Cristhian Ruiz, Gerard Corominas, Daniella Nunes, Claudia Roca, Nadina Latorre, Lizbeth Yataco, Maricelys Cruz, Nerea Blanco, Santiago Castejón, Dolores Cocho Calderón, Claustre Pont Sunyer, Jordi Espinosa Garcia, Rodrigo Paz Martin, Albert de Luis Sanchez, Dolores Espinosa Vivas, Juan Valencia Molina, Gemma, Planels Palome, Laia Tomas Chaume, Ares Villagrasa Vilella, Marco Bustamante, Anunciación Boltes, Fernando Rodríguez, Itziar Arrieta, Jordi Ciurans Molist, Barnés Andreu, Ernest Palomeras Soler, Nicolau Guanyabens Buscà, Manuel Daza López, Jordi Bigas Farreres, Virginia Casado Ruiz, Desiree Muriana Batiste, Mª Pilar Sanz Cartagena, Eulalia Cabot de Vega, Josep Bassa Real, Hector Pelaez Roman, César Socolich, Josep Mª Alonso Camp, Antonio Tomás Cano Orgaz, Mª Pilar Fossas Felip, Nicolás Morón, Sandra Bacca, Mauricio Molina, Francesc Casarramona, Lorena Elias, Muhammad Zidane Bukaei, Jose Antonio Martos Gutierrez, Judith Lopez Escuin, Cristina Olaizola, Yolexis López Vargas, Juan Jiménez Oyonarte, Rashida Soultana, Eduardo Sanjurjo Golpe, Esther Salvador, Guillem Vila, Marcos Serrano, Matilde Nuria López Claverol, Marian Lamolla, Miquel Amate, Adriana Rodriguez, Ruth Romero, Montgomery del Carpio, Ana Isabel Hernandez, Julián Martín, M Carmen Rosas, Antonio Nogueroles, Sorilandy Encarnación, Augusto Robles, Jose Antonio Herrera, Roger Gavilán, Toghrol Mameghani, Gastón Araujo, M.Angeles Garrido Morales, Enric Ramon Albert Segui, Eva Fernandez Climent, Francesc Paris Pujol, Mireia Judit Garrofé Seira, Lucía Gómez Pía, Fernando Salleres Nuñez, Cristina Aguar Peñalver, Cristina Vaz Lopes, Elisenda Ribera Tasa, Carmen Repullo Vilchez, Modesto Sánchez Zambrana, Beatriu Suescun Ribas, Inés Vilà Panés, Montserrat Vila Planavila, Alicia Vaqueiro Lorenzo, Meritxell Sabartés Guixes, Jorge Medina, David Sambrano, Javi Zamarreño, Carmen Pirela, Paola Vélez, Luis Cajamarca, Honey Pérez, Yarles Martínez, Jesus Alexander Gonçalves, Carles Regordosa, Claudia Mormeneo, Laura Griu, Maria Francia Colina, Enric Farik, Dolors Carrión Duch, Carles Badenas, Oscar Bernal, Núria Agramunt, Shyrlei Morales, Victoria Reynoso, Miguel Guerrero, Primitivo Romera Cid, Mònica Folqué, Claudia Pedroza, Adnan Hachem, Íñigo Soteras Martínez, Xavier Verdera García, Mercè López Amorós, Xavier Costa Subirós, Marta Cufí Benet, Cecile Van Eendenburg, Teresa Osuna, Dra Gina Santos, Mireia Pallisera, Lluís Gonzalo Oliva, Gemma Sanchez, Xavier Basurto, Ludgi Vivoda, Richard Van der Kleyn, Laura Robles, Ana Cabanelas Barranco, Mª Cruz Almendros, Marc Pérez Oliveras, Amelia Fernández Álvarez, Maria Rybyeva, Antoni Viñas, Maria Barcons, Joaquim Danès Alberto Tavera, Pablo Burbano, Cintie López, David Cruz, Paula Bisbe, Nora Fernández, Juan Carlos Palacio, Eduardo Fraiz, Oriol Aguiló, Rollmy Amorodjo, John Velázquez, Elena Sánchez, Jaume Español, Judit Perez de Celis, Anna Coll, Glòria Díaz, Margarida Vergés i Sala, Mª Ángels Casas Capdevila, Yosmairy Yoselin Ferrini, Aitor Gorriz, Diego-Javier Cucurell Navarro, Dulce Velásquez, Jaume Pla Soler, Josep González, Julian David Higuera, Lina Cuellar, Liza Margarita Miniello, Lluis Pujol, Sorin Cracan, Mora Vives, M Angela, Lopez Lopez, null Anabel, Montse Gorchs Molist, Delofeu Anna, Silvia Solà Muñoz, Ferreres Yolanda, Carol Pujalte, Elisabeth Téllez Marín, Yolanda Font Casas, Sara Hernández Luque, Joaquim Mejias Sendra, Francesca Mellado Valero, Campos Escala, Galup De Lacanal, Lopez Diaz, Castillo Paramio, Català Estopà, Español Moreda, Calafell Majo, Carballo Almeida, Castro Naval, M Elena, Cregut Ruiz, Pere Lluis, Deulofeu Font, Fabregat Sanjuan, Joan Pere, Fontquerni Gorchs, Forés Bellés, Joan Antoni, Gomez Herrera, Juan Carlos, Hijazo Prades, Itzaina Torvisco, Marti Rovira, Obiols Gonzalez, Olive Cavero, Querol Gil, M Soledad, Rico Rodriguez, Rios Sambernardo, Ropero Molina, Jose Ramon, Sanchez Valero, Santos Arevalo, Maria Jose, Soto Garcia, Maria Angeles, Tebar Escribano, Torres Garcia, Pedro José, Verdes Carrion, M Isabel, Verge Lopez, Juan Jose, Lopez Canela, M Angeles, Lucas Guarque, Morales Alvarez, Jorge Arnulfo, Morell Fornieles, Subirats Gomez, Maria Teresa, Torello Masa, Val Lopez, Maria Mercedes, Palmero Reyes, Juan Manuel, Rodriguez Forne, Ruana Turiel, Sanchez Gonzalez, Sebastia Gornals, Abrio Rico, Albert Gual Falip, Aznar Oliveros, Brugues Perotti, Calvet Molinero, Catells Franco, Corrales Medina, Daroca Miro, Duran Marquez, Feliu Pradas, Figueras Casanova, Garcia Tortajada, Grajera Gallego, Azahara del Mar, Las Arroyo, Dulcenombre de Jesus, Laserreta Sanz, Llambrich Vidal, Monllao Corral, Morales de la Cruz, Moreno Blanco, Orejuela Orgaz, Piñana Suazo, Pons Minguillon, Rodríguez Gómez, José Carlos, Rodriguez Pereira, Sedo Porcel, Sevil Villar, Sierra Lopez, Torres Romero, Trepat Calveres, Ventura Arnella, Acera Gil, M Teresa, Biesot Vico, Castro Galea, Rosa Maria, Escorcia Chafer, Juan Antonio, Gil Faure, Hernandez Luque, Jimenez Delgado, Mallafre Gay, M. Angel, Olivares Sanzo, Pubill Fondevila, Sabate Fort, Segovia Agámez, Antonio Carlos, Turata Longaretti, Valle Hernandez, Trayner Guixens, Aguilar Valor, Aguirre Alvarez, Alastrue Naval, Alferez Baquero, Alonso Marne, Cristina, Aloy Orozco, Alvarez Colino, Alvarez Peñuela, Ameller Cirilo, Maria Vanessa, Andujar Guerrero, Estefania Remedios, Auladell Sillero, Azcarate Sorbet, Basany Genesca, Benavent Barduena, Benito Tudela, Blanch Pardo, Boluda Pla, Bonilla Gonzalez, Bru Serramalera, Burnat Andreu, Caballero Calvo-Rayo, Calvo Casellas, Camps Mombiela, Cano Bresme, Carcelen Fernandez, Caro Solà, Casasas Matavacas, Castanedo Bolado, Cerdeña Cortina, Abella Jane, Laia Collado Borrego, Colom Orri, Comellas Vilanova, Conillera Sole, Cots Torres, Cuchi Estepa, de Sostoa Graell, del Rio Lopez, Delgado Compte, Diaz Bueno, Diaz Maneiro, Andrea Lucia, Domenech Palau, M. Carme, Duran Carasso, Pablo Javier, El Abidi, Escoda Martin, Esteve Casanovas, Fernandez Perez, Ferre Quintero, Flores Escobar, Fontcuberta Abad, Fortes del Valle, Mª Luisa, Franco Quesada, Sara Maria, Franco Romero, Gallego Francisco, Gamiz Gala, Alicia, Garcia Castañeda, Garcia Rodriguez, Casajuana Gemma, Gomez Arroyo, Gomez Girbau, Gonzalez Fernandez, Gonzalez Gonzalez, Gonzalez Lopez, Gual Obeso, Guerrero Blanco, Guillemas Roca, Guillermo Eudaldo, Hernandez Sebastia, Homar Covas, Hostench Alvarez, Huerta Royo, Ibañez Barcelo, Izquiero Cruz, Jaione Urdangarin Etxetxikia, Juárez Gimenez, Khlifi Alami, Laparra Gasco, Lara Moreales, Lasaosa Medina, Maria Lourdes, Lazaro Cava, Leon Berrar, López Maturana, Lopez Ramirez, López Romero, Lorente Marco, Lorenzo Martin, Lozano Casals, Lujan Nicola, Madrid Diaz, Jose Antonio, Maria Teresa Peris Morales, Marti Clemente, Martinez Castaño, David Natanael, Martinez Gamez, Martinez Gonzalez, Martinez Quesada, Maria de la Cabeza, Marzà Fusté, Mireia, M Conillera, Melendo Lasheras, Miralles Mestre, Montserrat Puig Pastalle, Montserrate Vidal, Mora Mellado, Morales Ponce, Morera Cabre, Morera Vivet, Mundi Souza, Muñoz Quiles, Navea Rosa, Neira Iglesias, M Asuncion, Nuñez Manrique, Mª Pilar, Obiols Martinez, Pallares Reig, Partegas Torres, Pascual Berengueras, Perez Gamez, Perez Oset, Perez Restrepo, Maria Alejandra, Planas Yeste, Planells Mangado, Puertas Carbonell, Quinteiro Blanco, Rebollar Benavente, Recasens Fernandez, Reyes Gomez, Maria del Carmen, Roca Pou, Rodriguez Ferrer, Rodriguez Franco, Rodriguez Fuertes, Rodriguez Muñoz, Rodriguez Navarro, Roig Iniesta, Romero Gracia, Rovira Brunet, Rovira de Eugenio, Rubio Baena, Ruiz Llorens, Sala Llamazares, San Juan Alaez, Sanchez Segura, Santasusana Soldevilla, Sanz Salmeron, Segura Perez, Serra Balcells, Sorina Dumitras, Teixidor Montoya, Tena Vicente, Tierno Salinas, Ester Ines, Toledo Testa, Tomàs Figueras, Tomas Ruperez, Torrano Garcia-Penche, Torres Esparza, Florenc Uku, Vazquez Blanco, Vazquez De la Paz, Vazquez Gil, Vazquez Gonzalez, Vidal Meler, Vilalta Cots, Vilches Jimenez, Visser Fernandez, Viu Gavin, Vives Vives, Carmona Jimenez, Francisco Jose, Galobardes Vilches, Gonzalez Gomez, Jodar Manzanera, Marimon Cortes, Marrodan Orive, Martin Bosch, Martorell Lopez, Millares Roca, M Jesus, Miralles Guri, Muliterno Hernandez, Muñoz Oliva, Pons Pujol, Postius Conde, Prieto Arruñada, Quintana Mathé, Rosell Mata, Alvarin Alvarez, Arrufat Flores, Bañuelos Pago, Campo Vilar, Cardus Hidalgo, Castello Gil, Maria Gloria, Castrillo Montsesinos, Clave Garces, Comes Sanroma, Descalzo Sequi, Errando Ricol, Escudero Campillo, Maria del Mar, Fernandez Alvarez, Fernandez Gomez, Franch Espinosa, Freixes Graells, Garcia Plaza, Garcia-Marron Gallego, Hernandez Simancas, Jaraba Armas, Jimenez Ramos, Lopez Oganissian, Madrona Romero, M Rosa, Martinez Millan, Martínez Morón, Merchan Encinas, Moreno Jimenez, Muñoz Rico, Navarro Rodriguez, Nogales Ibañez, Rita Maria, Novillo Viera, Parella Torrabadella, Mari Alba, Pera Villar, Carla Montserrat, Rabella Miralles, Ramis Trilles, Ribera Ortiz, Sastre Perez, Soro Borrega, Tapia Fores, Tellez Bernad, Trenado Alvarez, Felix Martin, Herrero Perez, Lanau Fuster, Lopez Gomariz, Pardo Lozano, Quintana Altimiras, Ventosa Lopez, Almodovar Damian, Alvarez Monterroso, Arambudo Comas, Boullon Garzon, Burgos Capella, Campuzano Garcia, Maria Del Mar, Capdevila Olivas, Carre Marti, Clara Isabel, Carretero Bacaicoa, Cazorla Calderon, Chacon Osuna, Cortes Planas, Cortit Olio, Delhomme Estany, Fructuos Martinez, Garcia Lopez, Pascual Luis, Genis Amill Vallve, Gonzalez Muñoz, Hernaez Ventura, Lavernia Gimenez, Martin Rojo, Martínez Medina, Mayol Barrera, Mercader Pi, Merino Dalmau, Miguel Campodarbe, Moreno Sanchez, Francisco Javier, Alba Mari, Penela Barrameda, Prieto Ajenjo, Rodriguez Pareja, Rodríguez Piñar, Javier Francisco, Rodriguez Tello, Romero Pereda, Sainz Saborido, Santacana Martin, Santos Martinez, Sierra Chavez, Turbau Torres, Vicente Domenech, Villena Esteo, Vives Pertegaz, Baena Gonzalez, Bagaria Pont, Beltran Sanchez, Bonet Alarcon, Borch Ballescà, Buhils Clanchet, Closa Garcia, Colomina Carril, Cristina Fernandez Sanchez, Fernandez Toledo Edurne Judith, Espases Rodriguez, Espert Resa, F Xavier, Fernández Sol, Gonzalez Lugo, Gracia Llesera, Herrada Lendinez, Juliench Liesa, Sandra Alicia, Lopez Ortega, Lopez Yuste, Lozano Villanueva, Lucia Sola Soto, Madrid Castellano, Megias Cano, Daniel Jesus, Montasell Ponce, Montesinos Sospedra, Moya Martinez, Muñoz Herrera, Ocaña Fernandez, Palau Bernal, Perez Sole, Ramon Carbonell, Ribas Lop, Rubio López, Rueda Lopez, Sabat Castaño, Sabata Lara, Salmerón Ramírez, Serra Creus, Serrano Dalmau, Sumasi Mainero, Gonzalo Gabriel, Valencia Primo, Ana Maria Viñuales Muñoz, Josep Roig, and Verònica Hidalgo.

Subjects
Stroke, Advanced and Specialized Nursing, Treatment Outcome, Endovascular Procedures, Humans, Neurology (clinical), Cardiology and Cardiovascular Medicine, Brain Ischemia, Ischemic Stroke, Thrombectomy, Workflow
Abstract

Background: We aim to compare the outcome of patients from urban areas, where the referral center is able to perform thrombectomy, with patients from nonurban areas enrolled in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion). Methods: Patients with suspected large vessel occlusion stroke, as evaluated by a Rapid Arterial Occlusion Evaluation score of ≥5, from urban catchment areas of thrombectomy-capable centers during RACECAT trial enrollment period were included in the Stroke Code Registry of Catalonia. Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with an ischemic stroke. Secondary outcomes included mortality at 90 days, rate of thrombolysis and thrombectomy, time from onset to thrombolysis, and thrombectomy initiation. Propensity score matching was used to assemble a cohort of patients with similar characteristics. Results: The analysis included 1369 patients from nonurban areas and 2502 patients from urban areas. We matched 920 patients with an ischemic stroke from urban areas and nonurban areas based on their propensity scores. Patients with ischemic stroke from nonurban areas had higher degrees of disability at 90 days (median [interquartle range] modified Rankin Scale score, 3 [2–5] versus 3 [1–5], common odds ratio, 1.25 [95% CI, 1.06–1.48]); the observed average effect was only significant in patients with large vessel stroke (common odds ratio, 1.36 [95% CI, 1.08–1.65]). Mortality rate was similar between groups(odds ratio, 1.02 [95% CI, 0.81–1.28]). Patients from nonurban areas had higher odds of receiving thrombolysis (odds ratio, 1.36 [95% CI, 1.16–1.67]), lower odds of receiving thrombectomy(odds ratio, 0.61 [95% CI, 0.51–0.75]), and longer time from stroke onset to thrombolysis (mean difference 38 minutes [95% CI, 25–52]) and thrombectomy(mean difference 66 minutes [95% CI, 37–95]). Conclusions: In Catalonia, Spain, patients with large vessel occlusion stroke triaged in nonurban areas had worse neurological outcomes than patients from urban areas, where the referral center was able to perform thrombectomy. Interventions aimed at improving organizational practices and the development of thrombectomy capabilities in centers located in remote areas should be pursued. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02795962.

Published
2022

35. Is off-label thrombolysis safe and effective in a real-life primary stroke center? A retrospective analysis of data from a 5-year prospective database

Author

D. Sablot, F. Leibinger, A. Dutray, L. Van Damme, L. Nguyen Them, G. Farouil, C. Jebali, C. Arquizan, M.-J. Ibanez-Julia, A. Laverdure, T. Allou, W. Chaabane, B. Fadat, N. Olivier, P. Smadja, M. Tardieu, M. Lachcar, J. Mas, A. Ousji, S. Jurici, I. Mourand, A. Ferraro, A. Dumitrana, Z.M. Bensalah, F. Damon, O.-A. Tincau, D. Valverde, V. Mekue-Fotso, A. Bonafe, L. Ortega, and N. Gaillard

Subjects
Stroke, Treatment Outcome, Fibrinolytic Agents, Neurology, Humans, Thrombolytic Therapy, Neurology (clinical), Brain Ischemia, Retrospective Studies, Ischemic Stroke, Cerebral Hemorrhage
Abstract

Intravenous thrombolysis (IVT) use for acute ischemic stroke (AIS) varies among countries, partly due to guidelines and product labeling changes. The study aim was to identify the characteristics of patients with AIS treated with off-label IVT and to determine its safety when performed in a primary stroke center (PSC).This observational, single-center study included all consecutive patients admitted to Perpignan PSC for AIS and treated with IVT and patients transferred for EVT, between January 1, 2015 and December 31, 2019. Data of patients treated with IVT according to ("in-label group") or outside ("off-label") the initial guidelines and manufacturer's product specification were compared. Safety was assessed using symptomatic intracerebral hemorrhage (SIH) as the main adverse event.Among the 892 patients in the database (834 screened by MRI, 93.5%), 746 were treated by IVT: 185 (24.8%) "in-label" and 561 (75.2%) "off-label". In the "off-label" group, 316 (42.4% of the cohort) had a single criterion for "off-label" use, 197 (26.4%) had two, and 48 (6.4%) had three or more criteria, without any difference in IVT safety pattern among them. SIH rates were comparable between the "off-label" and "in-label" groups (2.7% vs. 1.1%, P=0.21); early neurological deterioration and systematic adverse event due to IVT treatment were similar in the 2 groups. "Off-label" patients had higher in-hospital (8.7% vs. 3.8%, P=0.05) and 3-month mortality rates (12.1% vs 5.4%, P0.01), but this is explained by confounding factors as they were older (76 vs 67 years, P0.0001) and more dependent (median modified Rankin scale score 0.4 vs 0.1, P0.0001) at admission."Off-label" thrombolysis for AIS seems to be safe and effective in the routine setting of a primary stroke center.

Published
2022

36. Efficacy, safety, and immunogenicity of a booster regimen of Ad26.COV2.S vaccine against COVID-19 (ENSEMBLE2): results of a randomised, double-blind, placebo-controlled, phase 3 trial

Author

Karin Hardt, An Vandebosch, Jerald Sadoff, Mathieu Le Gars, Carla Truyers, David Lowson, Ilse Van Dromme, Johan Vingerhoets, Tobias Kamphuis, Gert Scheper, Javier Ruiz-Guiñazú, Saul N Faust, Christoph D Spinner, Hanneke Schuitemaker, Johan Van Hoof, Macaya Douoguih, Frank Struyf, Brian T. Garibaldi, Timothy E. Albertson, Christian Sandrock, Janet S. Lee, Mark R. Looney, Victor F. Tapson, Charles Shey Wiysonge, Luis Humberto Anaya Velarde, Daniel Backenroth, Jisha Bhushanan, Börries Brandenburg, Vicky Cárdenas, Bohang Chen, Fei Chen, Polan Chetty, Pei-Ling Chu, Kimberly Cooper, Jerome Custers, Hilde Delanghe, Anna Duca, Tracy Henrick, Jarek Juraszek, Catherine Nalpas, Monika Peeters, Jose Pinheiro, Sanne Roels, Martin F. Ryser, Jose Salas, Samantha Santoro Matias, Ilse Scheys, Pallavi Shetty, Georgi Shukarev, Jeffrey Stoddard, Willem Talloen, NamPhuong Tran, Nathalie Vaissiere, Elisabeth van Son-Palmen, Jiajun Xu, Erin A. Goecker, Alexander L. Greninger, Keith R. Jerome, Pavitra Roychoudhury, Simbarashe G. Takuva, Jose Luis Accini Mendoza, Eric Achtyes, Habibul Ahsan, Azhar Alhatemi, Nancy Allen, Jose R. Arribas, Ghazaleh Bahrami, Lucia Bailon, Ali Bajwa, Jonathan Baker, Mira Baron, Susana Benet, Driss Berdaï, Patrick Berger, Todd Bertoch, Claire Bethune, Sybille Bevilacqua, Maria Silvia Biagioni Santos, Ian Binnian, Karen Bisnauthsing, Jean-Marc Boivin, Hilde Bollen, Sandrine Bonnet, Alberto M. Borobia, Elisabeth Botelho-Nevers, Phil Bright, Vianne Britten, Claire Brown, Amanda Buadi, Erik Buntinx, Lesley Burgess, Larry Bush, Maria Rosario Capeding, Quito Osuna Carr, Amparo Carrasco Mas, Hélène Catala, Katrina Cathie, T. Shawn Caudill, Fernando Cereto Castro, Kénora Chau, Steven Chavoustie, Marie Chowdhury, Nicolas Chronos, Paola Cicconi, Liliana Cifuentes, Sara Maria Cobo, Helen Collins, Hayley Colton, Carlos Rolando G. Cuaño, Valentino D'Onofrio, Paul Dargan, Thomas Darton, Peter Deane, Jose Luis Del Pozo, Inge Derdelinckx, Amisha Desai, Michael Dever, Beatriz Díaz-Pollán, Mark DiBuono, Matthew Doust, Christopher Duncan, Jose Maria Echave-Sustaeta, Frank Eder, Kimberly Ellis, Stanton Elzi, Stevan Emmett, Johannes Engelbrecht, Mim Evans, Theo Farah, Timothy Felton, João Pedro Ferreira, Catherine Floutier, Patrick Flume, Stacy Ford, Veronica Fragoso, Andrew Freedman, Emilia Frentiu, Christopher Galloway, Florence Galtier, Julia Garcia Diaz, Irene García García, Alcaide Garcia, Zoe Gardener, Pascale Gauteul, Steven Geller, Andrew Gibson, Claudia Gillet, Nicolas Girerd, Pierre-Olivier Girodet, Maria Tarcela Gler, Richard Glover, Herschel Don D. Go, Karishma Gokani, Damien Gonthier, Christopher Green, Richard Greenberg, Carl Griffin, Coert Grobbelaar, Adonis Guancia, Gloria Hakkarainen, James Harris, Michael Hassman, Deirdre Heimer, Elizabeth Hellstrom-Louw, Yoan Herades, Christopher Holroyd, Nazreen Hussen, Marie Grace Dawn Isidro, Yvonne Jackson, Manish Jain, Esaú Custódio João Filho, Daniel Johnson, Ben Jones, Natasha Joseph, Analyn Jumeras, Patricia Junquera, Johanna Kellett-Wright, Patrick Kennedy, Paul E. Kilgore, Kenneth Kim, Murray Kimmel, George Konis, Mark Kutner, Karine Lacombe, Odile Launay, Rajeka Lazarus, Samuel Lederman, Gigi Lefebvre, Katrina Lennon Collins, Isabel Leroux-Roels, Kenneth Wilson O. Lim, Muriel Lins, Edward Liu, Martin Llewelyn, Akbar Mahomed, Bernardo Porto Maia, Alícia Marín-Candon, Xavier Martínez-Gómez, Jean Benoit Martinot, Andrea Mazzella, Frank McCaughan, Louise McCormack, John McGettigan, Purvi Mehra, Rhonda Mejeur, Vicki Miller, Anthony Mills, Jose Molto Marhuenda, Prebashan Moodley, Marta Mora-Rillo, Beatriz Mothe, Daniel Mullan, Alasdair Munro, Paul Myers, Jeremy Nell, Tamara Newman Lobato Souza, Jane A. O'Halloran, Maria Dolores Ochoa Mazarro, Abigail Oliver, Jose Millan Onate Gutierrez, Jessica Ortega, Masaru Oshita, Susana Otero Romero, Jeffrey Scott Overcash, Daniel Owens, Alice Packham, Mihaela Pacurar, Leonardo Paiva de Sousa, Adrian Palfreeman, Christian José Pallares, Rahul Patel, Suchet Patel, Leslie Pelkey, Denise Peluso, Florentina Penciu, S. Jerry Pinto, Kevin Pounds, Joe Pouzar, Antoinette Pragalos, Rachel Presti, David Price, Ehsaan Qureshi, José Valdez Ramalho Madruga, Mayur Ramesh, Bruce Rankin, Béatrice Razat, Breno Riegel Santos, Robert Riesenberg, Ernie Riffer, Siobhan Roche, Katie Rose, Pietro Rosellini, Patrick Rossignol, Beth Safirstein, Hernan Salazar, Gregorio Sanchez Vallejo, Smrithi Santhosh, Enrique Seco-Meseguer, Michael Seep, Emma Sherry, Philip Short, Patrick Soentjens, Joel Solis, Alejandro Soriano Viladomiu, Caroline Sorli, Selwyn Spangenthal, Niamh Spence, Elaine Stephenson, Cynthia Strout, Ronald Surowitz, Kristy Michelle Taladua, David Tellalian, Claire Thalamas, Nang Thiriphoo, Judith Thomas, Nicholas Thomas, Guillermo Trout, Mikel Urroz, Bernard Veekmans, Laurent Veekmans, Ralph Elvi M. Villalobos, Sarah Warren, Brian Webster, Alexander White, Gail Williams, Hayes Williams, Barbara Wilson, Alan Winston, Martin Wiselka, and Marcus Zervos

Subjects
Adult, Vaccines, COVID-19 Vaccines, Immunogenicity, Vaccine, Infectious Diseases, Adolescent, Ad26COVS1, Double-Blind Method, SARS-CoV-2, Humans, COVID-19, Antibodies, Viral
Abstract

Despite the availability of effective vaccines against COVID-19, booster vaccinations are needed to maintain vaccine-induced protection against variant strains and breakthrough infections. This study aimed to investigate the efficacy, safety, and immunogenicity of the Ad26.COV2.S vaccine (Janssen) as primary vaccination plus a booster dose.ENSEMBLE2 is a randomised, double-blind, placebo-controlled, phase 3 trial including crossover vaccination after emergency authorisation of COVID-19 vaccines. Adults aged at least 18 years without previous COVID-19 vaccination at public and private medical practices and hospitals in Belgium, Brazil, Colombia, France, Germany, the Philippines, South Africa, Spain, the UK, and the USA were randomly assigned 1:1 via a computer algorithm to receive intramuscularly administered Ad26.COV2.S as a primary dose plus a booster dose at 2 months or two placebo injections 2 months apart. The primary endpoint was vaccine efficacy against the first occurrence of molecularly confirmed moderate to severe-critical COVID-19 with onset at least 14 days after booster vaccination, which was assessed in participants who received two doses of vaccine or placebo, were negative for SARS-CoV-2 by PCR at baseline and on serology at baseline and day 71, had no major protocol deviations, and were at risk of COVID-19 (ie, had no PCR-positive result or discontinued the study before day 71). Safety was assessed in all participants; reactogenicity, in terms of solicited local and systemic adverse events, was assessed as a secondary endpoint in a safety subset (approximately 6000 randomly selected participants). The trial is registered with ClinicalTrials.gov, NCT04614948, and is ongoing.Enrolment began on Nov 16, 2020, and the primary analysis data cutoff was June 25, 2021. From 34 571 participants screened, the double-blind phase enrolled 31 300 participants, 14 492 of whom received two doses (7484 in the Ad26.COV2.S group and 7008 in the placebo group) and 11 639 of whom were eligible for inclusion in the assessment of the primary endpoint (6024 in the Ad26.COV2.S group and 5615 in the placebo group). The median (IQR) follow-up post-booster vaccination was 36·0 (15·0-62·0) days. Vaccine efficacy was 75·2% (adjusted 95% CI 54·6-87·3) against moderate to severe-critical COVID-19 (14 cases in the Ad26.COV2.S group and 52 cases in the placebo group). Most cases were due to the variants alpha (B.1.1.7) and mu (B.1.621); endpoints for the primary analysis accrued from Nov 16, 2020, to June 25, 2021, before the global dominance of delta (B.1.617.2) or omicron (B.1.1.529). The booster vaccine exhibited an acceptable safety profile. The overall frequencies of solicited local and systemic adverse events (evaluated in the safety subset, n=6067) were higher among vaccine recipients than placebo recipients after the primary and booster doses. The frequency of solicited adverse events in the Ad26.COV2.S group were similar following the primary and booster vaccinations (local adverse events, 1676 [55·6%] of 3015 vs 896 [57·5%] of 1559, respectively; systemic adverse events, 1764 [58·5%] of 3015 vs 821 [52·7%] of 1559, respectively). Solicited adverse events were transient and mostly grade 1-2 in severity.A homologous Ad26.COV2.S booster administered 2 months after primary single-dose vaccination in adults had an acceptable safety profile and was efficacious against moderate to severe-critical COVID-19. Studies assessing efficacy against newer variants and with longer follow-up are needed.Janssen ResearchDevelopment.

Published
2022

37. Helicobacter pylori-negative Chronic Gastritis in Children

Author

Amit Assa, Osvaldo Borrelli, Ilse Broekaert, Marco Deganello Saccomani, Jernej Dolinsek, Javier Martin-de-Carpi, Emmanuel Mas, Erasmo Miele, Sara Sila, Mike Thomson, Christos Tzivinikos, Marc A. Benninga, Pediatric surgery, Paediatric Gastroenterology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam Reproduction & Development (AR&D), Assa, Amit, Borrelli, Osvaldo, Broekaert, Ilse, Saccomani, Marco Deganello, Dolinsek, Jernej, Martin-de-Carpi, Javier, Mas, Emmanuel, Miele, Erasmo, Sila, Sara, Thomson, Mike, Tzivinikos, Christo, and Benninga, Marc A

Subjects
Adult, Cross-Sectional Studies, Helicobacter pylori, Gastritis, Pediatrics, Perinatology and Child Health, Eosinophilia, Gastroenterology, Humans, Child, Enteritis, Helicobacter Infections
Abstract

OBJECTIVES: To systematically review the current evidence on Helicobacter pylori-negative chronic gastritis including natural history, available therapies and outcomes. METHODS: Articles providing data on the prevalence, treatment or outcomes of Helicobacter pylori-negative gastritis were identified through a systematic search in the MEDLINE and EMBASE databases. All original research articles from human studies until October 31, 2021, were included. RESULTS: A total of 54 studies were included consisted of eosinophilic gastritis (n = 9), autoimmune gastritis (n = 11), collagenous gastritis (n = 16), focally enhanced gastritis (n = 6), lymphocytic gastritis (n = 5) and other causes including idiopathic gastritis and chronic renal failure related (n = 7). Most of the included studies were either cross-sectional or longitudinal cohorts except for collagenous gastritis, which mainly included case reports and case series. The prevalence of paediatric eosinophilic gastritis ranges between 5 and 7/100,000 and patients have generally favourable outcome with 50% to 70% clinical and histological response to either corticosteroids or elimination diets. Autoimmune gastritis and collagenous gastritis are extremely rare entities, commonly present with refractory iron deficiency anaemia, while lymphocytic gastritis is relatively common (10%-45%) in children with coeliac disease. Data on treatments and outcomes of autoimmune, collagenous, and focally enhanced gastritis are lacking with limited data implying poor response to therapy in the former 2 diagnoses. CONCLUSIONS: Helicobacter pylori-negative gastritis is uncommonly reported, mainly in small cohorts, mixed adult-paediatric cohorts or as sporadic case reports. As common symptoms are not specific, thus not always result in an endoscopic evaluation, the true prevalence of these distinct disorders may be underestimated, and thus under reported.

Published
2022

38. Training in Paediatric Clinical Nutrition Across Europe

Author

Alexandra Papadopoulou, Carmen Ribes-Koninckx, Alastair Baker, Maria Noni, Eleni Koutri, Maria-Vasiliki Karagianni, Sue Protheroe, Alfredo Guarino, Emmanuel Mas, Michael Wilschanski, Enriqueta Roman, Johanna Escher, Raoul I. Furlano, Carsten Posovszky, Ilse Hoffman, Gabor Veres, Jiri Bronsky, Almuthe Christine Hauer, Duska Tjesic-Drinkovic, Maria Fotoulaki, Rok Orel, Vaidotas Urbonas, Aydan Kansu, Miglena Georgieva, Berthold Koletzko, Papadopoulou, Alexandra, Ribes-Koninckx, Carmen, Baker, Alastair, Noni, Maria, Koutri, Eleni, Karagianni, Maria-Vasiliki, Protheroe, Sue, Guarino, Alfredo, Mas, Emmanuel, Wilschanski, Michael, Roman, Enriqueta, Escher, Johanna, Furlano, Raoul I, Posovszky, Carsten, Hoffman, Ilse, Veres, Gabor, Bronsky, Jiri, Hauer, Almuthe Christine, Tjesic-Drinkovic, Duska, Fotoulaki, Maria, Orel, Rok, Urbonas, Vaidota, Kansu, Aydan, Georgieva, Miglena, Koletzko, Berthold, and Pediatrics

Subjects
Europe, children, clinical nutrition training, training in paediatric gastroenterology, hepatology and nutrition, Surveys and Questionnaires, Pediatrics, Perinatology and Child Health, Gastroenterology, Humans, Child, Child Nutritional Physiological Phenomena, Societies, Medical
Abstract

OBJECTIVES/BACKGROUND: Disease-related malnutrition is common in patients with chronic diseases and has detrimental effects, therefore, skills in nutrition care are essential core competencies for paediatric digestive medicine. The aim of this survey, conducted as part of a global survey of paediatric gastroenterology, hepatology and nutrition (PGHN) training in Europe, was to assess nutrition care-related infrastructure, staff, and patient volumes in European PGHN training centres. METHODS: Standardized questionnaires related to clinical nutrition (CN) care were completed by representatives of European PGHN training centres between June 2016 and December 2019. RESULTS: One hundred training centres from 17 European countries, Turkey, and Israel participated in the survey. Dedicated CN clinics exist in 66% of the centres, with fulltime and part-time CN specialists in 66% and 42%, respectively. Home tube feeding (HTF) and home parenteral nutrition (HPN) programmes are in place in 95% and 77% of centres, respectively. Twenty-four percent of centres do not have a dedicated dietitian and 55% do not have a dedicated pharmacist attached to the training centre. Even the largest centres with >5000 outpatients reported that 25% and 50%, respectively do not have a dedicated dietitian or pharmacist. Low patient numbers on HTF and HPN of

Published
2022

39. Prognostic Impact of Unsupervised Early Assessment of Bulk and Leukemic Stem Cell Measurable Residual Disease in Acute Myeloid Leukemia

Author

Alban Canali, Inès Vergnolle, Sarah Bertoli, Laetitia Largeaud, Marie-Laure Nicolau, Jean-Baptiste Rieu, Suzanne Tavitian, Françoise Huguet, Muriel Picard, Pierre Bories, Jean Philippe Vial, Nicolas Lechevalier, Marie Christine Béné, Isabelle Luquet, Véronique Mansat-De Mas, Eric Delabesse, Christian Récher, and François Vergez

Subjects
Leukemia, Myeloid, Acute, Cancer Research, Neoplasm, Residual, Oncology, Stem Cells, Humans, Induction Chemotherapy, Prognosis
Abstract

Purpose: Acute myeloid leukemias (AML) are clonal diseases that develop from leukemic stem cells (LSC) that carry an independent prognostic impact on the initial response to induction chemotherapy, demonstrating the clinical relevance of LSC abundance in AML. In 2018, the European LeukemiaNet published recommendations for the detection of measurable residual disease (Bulk MRD) and suggested the exploration of LSC MRD and the use of multiparametric displays. Experimental Design: We evaluated the performance of unsupervised clustering for the post-induction assessment of bulk and LSC MRD in 155 patients with AML who received intensive conventional chemotherapy treatment. Results: The median overall survival (OS) for Bulk+ MRD patients was 16.7 months and was not reached for negative patients (HR, 3.82; P < 0.0001). The median OS of LSC+ MRD patients was 25.0 months and not reached for negative patients (HR, 2.84; P = 0.001). Interestingly, 1-year (y) and 3-y OS were 60% and 39% in Bulk+, 91% and 52% in Bulk-LSC+ and 92% and 88% in Bulk-LSC−. Conclusions: In this study, we confirm the prognostic impact of post-induction multiparametric flow cytometry Bulk MRD in patients with AML. Focusing on LSCs, we identified a group of patients with negative Bulk MRD but positive LSC MRD (25.8% of our cohort) with an intermediate prognosis, demonstrating the interest of MRD analysis focusing on leukemic chemoresistant subpopulations.

Published
2022

40. Factor XIa inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke): an international, randomised, double-blind, placebo-controlled, phase 2b trial

Author

Ashkan Shoamanesh, Hardi Mundl, Eric E Smith, Jaime Masjuan, Ivan Milanov, Teruyuki Hirano, Alina Agafina, Bruce Campbell, Valeria Caso, Jean-Louis Mas, Qiang Dong, Peter Turcani, Hanne Christensen, Jose M Ferro, Roland Veltkamp, Robert Mikulik, Gian Marco De Marchis, Thompson Robinson, Robin Lemmens, Adam Stepien, Stefan Greisenegger, Risto Roine, Laszlo Csiba, Pooja Khatri, Jonathan Coutinho, Arne G Lindgren, Andrew M Demchuk, Pablo Colorado, Bodo Kirsch, Christoph Neumann, Laura Heenan, Lizhen Xu, Stuart J Connolly, Robert G Hart, Neurology, ACS - Atherosclerosis & ischemic syndromes, and ANS - Neurovascular Disorders

Subjects
Male, Anticoagulants, Hemorrhage, Thrombosis, General Medicine, Factor XIa, Brain Ischemia, Stroke, Treatment Outcome, Double-Blind Method, Humans, Female, Platelet Aggregation Inhibitors, Aged, Ischemic Stroke
Abstract

Background: Asundexian (Bayer AG, Leverkusen, Germany), an oral small molecule factor XIa (FXIa) inhibitor, might prevent thrombosis without increasing bleeding. Asundexian's effect for secondary prevention of recurrent stroke is unknown. Methods: In this randomised, double-blind, placebo-controlled, phase 2b dose-finding trial (PACIFIC-Stroke), patients with acute (within 48 h) non-cardioembolic ischaemic stroke were recruited from 196 hospitals in 23 countries. Patients were eligible if they were aged 45 years or older, to be treated with antiplatelet therapy, and able to have a baseline MRI (either before or within 72 h of randomisation). Eligible participants were randomly assigned (1:1:1:1), using an interactive web-based response system and stratified according to anticipated antiplatelet therapy (single vs dual), to once daily oral asundexian (BAY 2433334) 10 mg, 20 mg, or 50 mg, or placebo in addition to usual antiplatelet therapy, and were followed up during treatment for 26–52 weeks. Brain MRIs were obtained at study entry and at 26 weeks or as soon as possible after treatment discontinuation. The primary efficacy outcome was the dose–response effect on the composite of incident MRI-detected covert brain infarcts and recurrent symptomatic ischaemic stroke at or before 26 weeks after randomisation. The primary safety outcome was major or clinically relevant non-major bleeding as defined by International Society on Thrombosis and Haemostasis criteria. The efficacy outcome was assessed in all participants assigned to treatment, and the safety outcome was assessed in all participants who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04304508, and is now complete. Findings: Between June 15, 2020, and July 22, 2021, 1880 patients were screened and 1808 participants were randomly assigned to asundexian 10 mg (n=455), 20 mg (n=450), or 50 mg (n=447), or placebo (n=456). Mean age was 67 years (SD 10) and 615 (34%) participants were women, 1193 (66%) were men, 1505 (83%) were White, and 268 (15%) were Asian. The mean time from index stroke to randomisation was 36 h (SD 10) and median baseline National Institutes of Health Stroke Scale score was 2·0 (IQR 1·0–4·0). 783 (43%) participants received dual antiplatelet treatment for a mean duration of 70·1 days (SD 113·4) after randomisation. At 26 weeks, the primary efficacy outcome was observed in 87 (19%) of 456 participants in the placebo group versus 86 (19%) of 455 in the asundexian 10 mg group (crude incidence ratio 0·99 [90% CI 0·79–1·24]), 99 (22%) of 450 in the asundexian 20 mg group (1·15 [0·93–1·43]), and 90 (20%) of 447 in the asundexian 50 mg group (1·06 [0·85–1·32]; t statistic –0·68; p=0·80). The primary safety outcome was observed in 11 (2%) of 452 participants in the placebo group versus 19 (4%) of 445 in the asundexian 10 mg group, 14 (3%) of 446 in the asundexian 20 mg group, and 19 (4%) of 443 in the asundexian 50 mg group (all asundexian doses pooled vs placebo hazard ratio 1·57 [90% CI 0·91–2·71]). Interpretation: In this phase 2b trial, FXIa inhibition with asundexian did not reduce the composite of covert brain infarction or ischaemic stroke and did not increase the composite of major or clinically relevant non-major bleeding compared with placebo in patients with acute, non-cardioembolic ischaemic stroke. Funding: Bayer AG.

Published
2022

41. Electroconvulsive therapy effects on anhedonia and reward circuitry anatomy: A dimensional structural neuroimaging approach

Author

Joan A. Camprodon, Erik Lee, Marta Cano, Tracy Barbour, Kristen K. Ellard, Alexis Worthley, and Carles Soriano-Mas

Subjects
Anhedonia, media_common.quotation_subject, medicine.medical_treatment, Neuroimaging, behavioral disciplines and activities, Pleasure, Reward system, Electroconvulsive therapy, Reward, mental disorders, medicine, Humans, Valence (psychology), Electroconvulsive Therapy, Depression (differential diagnoses), media_common, Depressive Disorder, Major, medicine.disease, Magnetic Resonance Imaging, Psychiatry and Mental health, Clinical Psychology, Major depressive disorder, medicine.symptom, Psychology, psychological phenomena and processes, Clinical psychology
Abstract

Anhedonia is a core symptom of major depressive disorder (MDD) resulting from maladaptive reward processing. Electroconvulsive therapy (ECT) is an effective treatment for patients with MDD. No previous neuroimaging studies have taken a dimensional approach to assess whether ECT-induced volume changes are specifically related to improvements in anhedonia and positive valence emotional constructs. We aimed to assess the relationship between ECT-induced brain volumetric changes and improvement in anhedonia and reward processing in patients with MDD.We evaluated 15 patients with MDD before and after ECT. We used magnetic resonance imaging, clinical scales (i.e., Quick Inventory of Depressive Symptomatology for syndromal depression severity and Snaith-Hamilton Pleasure Scale for anhedonia) and the Temporal Experience of Pleasure Scale for anticipatory and consummatory experiences of pleasure. We identified 5 regions of interest within the reward circuit and a 6th control region relevant for MDD but not core to the reward system (Brodmann Area 25).Anhedonia, anticipatory and consummatory reward processing improved after ECT. Volume increases within the right reward system separated anhedonia responders and non-responders. Improvement in anticipatory (but not consummatory) reward correlated with increases in volume in hippocampus, amygdala, ventral tegmental area and nucleus accumbens.We evaluated a modest sample size of patients with concurrent pharmacological treatment using a subjective psychometric assessment.We highlight the importance of a dimensional and circuit-based approach to understanding target engagement and the mechanism of action of ECT, with the goal to define symptom- and circuit-specific response biomarkers for device neuromodulation therapies.

Published
2022

42. SALAI-Net: species-agnostic local ancestry inference network

Author

Benet, Oriol Sabat, Daniel, Mas Montserrat, Xavier, Giro-I-Nieto, Alexander G, Ioannidis, and Universitat Politècnica de Catalunya. Departament de Teoria del Senyal i Comunicacions

Subjects
Informàtica::Aplicacions de la informàtica::Bioinformàtica [Àrees temàtiques de la UPC], Statistics and Probability, Genome, Bioinformatics, Biochemistry, Computer Science Applications, Computational Mathematics, Dogs, Haplotypes, Bioinformàtica, Computational Theory and Mathematics, Local ancestry inference, Animals, Humans, Molecular Biology, Genome-Wide Association Study
Abstract

Availability and implementation: We provide an open source implementation and links to publicly available data at github.com/AI-sandbox/SALAI-Net. Data is publicly available as follows: https://www.internationalgenome.org (1000 Genomes), https://www.simonsfoundation.org/simons-genome-diversity-project (Simons Genome Diversity Project), https://www.sanger.ac.uk/resources/downloads/human/hapmap3.html (HapMap), ftp://ngs.sanger.ac.uk/production/hgdp/hgdp_wgs.20190516 (Human Genome Diversity Project) and https://www.ncbi.nlm.nih.gov/bioproject/PRJNA448733 (Canid genomes). Local ancestry inference (LAI) is the high resolution prediction of ancestry labels along a DNA sequence. LAI is important in the study of human history and migrations, and it is beginning to play a role in precision medicine applications including ancestry-adjusted genome-wide association studies (GWASs) and polygenic risk scores (PRSs). Existing LAI models do not generalize well between species, chromosomes or even ancestry groups, requiring re-training for each different setting. Furthermore, such methods can lack interpretability, which is an important element in each of these applications. We present SALAI-Net, a portable statistical LAI method that can be applied on any set of species and ancestries (species-agnostic), requiring only haplotype data and no other biological parameters. Inspired by identity by descent methods, SALAI-Net estimates population labels for each segment of DNA by performing a reference matching approach, which leads to an interpretable and fast technique. We benchmark our models on whole-genome data of humans and we test these models’ ability to generalize to dog breeds when trained on human data. SALAI-Net outperforms previous methods in terms of balanced accuracy, while generalizing between different settings, species and datasets. Moreover, it is up to two orders of magnitude faster and uses considerably less RAM memory than competing methods. This paper was published as part of a special issue financially supported by ECCB2022. Some of the computing for this project was performed on the Sherlock cluster at Stanford University. We would like to thank Stanford University and the Stanford Research Computing Center for providing computational resources and support that contributed to these research results. A.G.I. and D.M.M. received support from NIH under award R01HG010140. Conflict of Interest: AGI is a co-founder of Galatea Bio Inc. Peer Reviewed Objectius de Desenvolupament Sostenible::3 - Salut i Benestar Objectius de Desenvolupament Sostenible::3 - Salut i Benestar::3.4 - Per a 2030, reduir en un terç la mortalitat prematura per malalties no transmissibles, mitjançant la prevenció i el tractament, i promoure la salut mental i el benestar

Published
2022

44. Neutrophil to Lymphocyte Ratio in Patients With a First Episode of Psychosis: A Two-Year Longitudinal Follow-up Study

Author

Miquel, Bioque, Ana, Catarina Matias-Martins, Vicent, Llorca-Bofí, Gisela, Mezquida, Manuel J, Cuesta, Eduard, Vieta, Sílvia, Amoretti, Antonio, Lobo, Ana, González-Pinto, Carmen, Moreno, Alexandra, Roldán, Anabel, Martinez-Aran, Immaculada, Baeza, Daniel, Bergé, Clemente, García-Rizo, Sergi, Mas Herrero, Miquel, Bernardo, and Vicent, Balanzá

Subjects
Male, Psychiatry and Mental health, Psychotic Disorders, Neutrophils, Humans, Female, Prospective Studies, Lymphocytes, Follow-Up Studies
Abstract

Background and Hypothesis A pro-inflammatory phenotype has been related to psychotic disorders. The neutrophil-lymphocyte ratio (NLR) is an accessible biomarker that could be helpful to characterize this systemic inflammation state. Study Design This study evaluated the NLR in a cohort of 310 subjects with a first episode of psychosis (FEP) and a matched group of 215 healthy controls, recruited in 16 Spanish centers participating in the PEPs Project. We investigated the NLR measures over 2 years in a prospective, naturalistic study. Study Results At baseline, the FEP group showed a significant higher mean NLR compared to the control group (1.96 ± 1.11 vs 1.72 ± 0.74, P = 0.03). These ratio differences between groups grew at the 24 months follow-up visit (2.04 ± 0.86 vs 1.65 ± 0.65, P < 0.001). Within the FEP group, there were no significant differences in NLR across the follow-up visits, between genders or diagnosis groups (affective vs nonaffective). NLR values did not correlate with the Positive and Negative Symptoms Scale scores. The group of patients who did not reach remission criteria at the end of the study showed a significant higher NLR than those who remitted (2.1896 ± 0.85 vs 1.95 ± 0.87, P = 0.042). A significant correlation between antipsychotic doses and NLR was found at the two-years follow-up visit (r=0.461, P < 0.001). Conclusions Our results highlight the existence of an underlying predisposition of FEP patients to present an increased mean NLR. The use of NLR in clinical practice could be helpful to identify this inflammatory imbalance.

Published
2023

45. Caustic Ingestion: A Risk-Based Algorithm

Author

Joan, Tosca, Ana, Sánchez, Ana, Sanahuja, Rosana, Villagrasa, Paloma, Poyatos, Pilar, Mas, Isabel, Pascual, Paloma, Lluch, Belén, Herreros, Andrés, Peña, Vicente, Sánchiz, and Miguel, Mínguez

Subjects
Eating, Hepatology, Caustics, Burns, Chemical, Gastroenterology, Humans, Algorithms, Retrospective Studies
Abstract

Caustic ingestion management could be improved with a diagnostic approach based on risk factors. This study aimed to develop an algorithm derived from predictive factors of a poor clinical course, to evaluate its diagnostic accuracy and resource consumption, and to compare it with 2 other approaches, a radiological one based on computed tomography and a classical one based on symptoms and endoscopy.All patients older than 15 years presenting with caustic ingestion in our tertiary care hospital between 1995 and 2021 were prospectively included. Adverse outcome was defined as intensive care unit admission, emergency surgery, or death. Ingestion characteristics, symptoms, and laboratory and endoscopic findings were analyzed to determine the most relevant risk factors. Diagnostic accuracy and the number of examinations required were estimated and compared with the other 2 algorithms applied to our series.The sample included 532 cases of caustic ingestion, 13.2% (95% confidence interval [CI]: 10.3-16.0) of which had adverse outcomes. Volume and type of caustic substance; presence of symptoms and pharyngolaryngeal involvement; and neutrophilia, acidosis, and endoscopic injury were combined to develop an algorithm that would provide the highest diagnostic odds ratio (167.2; 95% CI: 71.9-388.7). Following this approach, half of the patients (50.6%; 95% CI: 46.2-55.1) would not require any examination and, overall, the need for endoscopy (20.0%; 95% CI: 16.4-23.5) and computed tomography (16.3%; 95% CI: 13.0-19.5) would be lower than that for the other 2 algorithms.A risk-based algorithm could improve caustic ingestion management by maintaining high diagnostic accuracy while reducing diagnostic test requirements.

Published
2022

46. Frailty, depression risk and 10-year hospitalization in older adults. The FRADEA study

Author

Marta Carolina Ruiz-Grao, Pedro Manuel Sánchez-Jurado, Milagros Molina-Alarcón, Miriam Garrido-Miguel, Celia Álvarez-Bueno, Rubén Alcantud-Córcoles, Fernando Andrés-Petrel, Almudena Avendaño-Céspedes, Cristina Gómez-Ballesteros, Victoria Sánchez-Flor- Alfaro, Rita López-Bru, Belén Roldán-García, María Teresa Tabernero-Sahuquillo, Marta Mas-Romero, Rafael García-Molina, Luis Romero-Rizos, and Pedro Abizanda

Subjects
Cohort Studies, Hospitalization, Frailty, Spain, Frail Elderly, Humans, Geriatric Assessment, Gerontology, Aged
Abstract

To determine whether the interaction between frailty status and depression risk is associated with hospitalization density in older adults.Ongoing cohort study in 794 subjects aged over 70 years from Albacete (Spain). Data were collected on depression risk, frailty, hospitalizations, and covariates. Participants were categorized into six groups.Adjusted hospitalization risk was higher for groups of prefrail/-non depression risk (HR 1.48; 95% confidence interval (CI) 1.16-1.89), prefrail/depression risk (HR 1.73; 95% CI 1.29-2.30), frail/non depression risk (HR 1.79; 95% CI 1.22-2.62), and frail/depression risk (HR 2.12; 95% CI 1.49-3.02), compared with robust/non depression risk group (p0.01). Frail and prefrail groups presented increased hospitalization density in the first four follow-up years.Depression risk changes the yearly probabilities of hospitalization in prefrail and frail groups, increasing them in the first years. Depression risk should be monitored in prefrail and frail older adults as an independent risk factor for hospitalization.

Published
2022

47. Secretory immunoglobulin A (s-IgA) reactivity to acute psychosocial stress in children and adolescents: The influence of pubertal development and history of maltreatment

Author

Laia Marques-Feixa, Águeda Castro-Quintas, Helena Palma-Gudiel, Soledad Romero, Astrid Morer, Marta Rapado-Castro, María Martín, Iñaki Zorrilla, Hilario Blasco-Fontecilla, Maite Ramírez, María Mayoral, Iría Mendez, Nerea San Martín-Gonzalez, María Rodrigo-Yanguas, José Luis Monteserín-García, Lourdes Fañanás, María José Muñoz, Eulalia Anglada, Ariadna Mas, María José Lobato, Pilar Santamarina, Silvia Gadea, Maddi Laborde, Carmen Moreno, Lydia Gayubo, and María Marín-Vila

Subjects
Hypothalamo-Hypophyseal System, Psychological tests, Adolescent, Hydrocortisone, Maltractament infantil, Endocrine and Autonomic Systems, Immunology, Adolescents, Teenagers, Tests psicològics, Immunoglobulina A, Immunoglobulin A, Behavioral Neuroscience, Immunoglobulin A, Secretory, Humans, Child, Saliva, Infants, Children, Stress, Psychological, Child abuse
Abstract

Background: Mucosal secretory immunoglobulin A (s-IgA) is an antibody protein-complex that plays a crucial role in immune first defense against infection. Although different immune biomarkers have been associated with stress-related psychopathology, s-IgA remains poorly studied, especially in youth. Objectives: The present study investigated how s-IgA behaves in front of acute psychosocial stress in children and adolescents, including possible variability associated with developmental stage and history of childhood maltreatment (CM). Methods: 94 children and adolescents from 7 to 17 years (54 with a current psychiatric diagnostic and 40 healthy controls) drawn from a larger Spanish study were explored (EPI-Young Stress Project). To assess biological reactivity, participants provided five saliva samples during an acute laboratory-based psychosocial stressor, the Trier Social Stress Test for Children (TSST-C). Samples were assayed for s-IgA, as well as for cortisol. Pubertal development was ascertained by Tanner stage and CM following TASSCV criteria. Results: We observed s-IgA fluctuations throughout the stressor, indicating the validity of TSST-C to stimulate s-IgA secretion (F(4,199) = 6.200, p

Published
2022

49. Discovery of the ARP2 protein as a determining molecule in tumor cell death

Author

Jaime Mas-Oliva and Juana Virginia Tapia-Vieyra

Subjects
Male, Cell type, Programmed cell death, DNA, Complementary, Xenopus, Apoptosis, CHO Cells, Metastasis, Cell membrane, Xenopus laevis, Cricetulus, LNCaP, medicine, Animals, Humans, RNA, Messenger, Ovum, biology, Chemistry, Chinese hamster ovary cell, Prostatic Neoplasms, General Medicine, biology.organism_classification, medicine.disease, medicine.anatomical_structure, Cancer research, Calcium, Calcium Channels, Apoptosis Regulatory Proteins
Abstract

Cancer is a multifactorial disease that constitutes a serious public health problem worldwide. Prostate cancer advanced stages are associated with the development of androgen-independent tumors and an apoptosis-resistant phenotype that progresses to metastasis. By studying androgen-independent lymphoid nodule carcinoma of the prostate (LNCaP) cells induced to apoptosis by serum elimination, we identified the activation of a non-selective cationic channel of 23pS conductance that promotes incoming Ca2+ currents, as well as apoptosis final stages. arp2cDNA was isolated and identified to be of the same cell type, and mRNA was expressed in Xenopus laevis oocytes, which was found to be associated with the activation of incoming Ca2+ currents and induction to apoptosis. cDNA, which encodes the ARP2 protein, was overexpressed in LNCaP cells and Chinese hamster ovary cells, which induced apoptosis. Our evidence suggests that protein ARP2 overexpression and transit to the cell membrane allows an increased Ca2+ incoming current that initiates the apoptosis process in epithelial-type cells whose phenotype shows resistance to programmed cell death.

Published
2023

50. Home‐based exercise programs in patients with chronic kidney disease: A systematic review and META‐analysis

Author

Anna Junqué‐Jiménez, Ariadna Morera‐Mas, Carmen Pérez‐Ventana‐Ortiz, Lola Andreu‐Periz, and Eva Segura‐Ortí

Subjects
Hand Strength, Quality of Life, Humans, General Medicine, Renal Insufficiency, Chronic, Exercise, General Nursing, Exercise Therapy
Abstract

Intradialysis exercise programs in renal patients result in improved functional capacity, muscle strength, symptoms of depression, and health-related quality of life. Home-based exercise programs are an alternative to overcome logistical and human resource problems. However, the implementation of these programs is not an easy task and there is a lack of knowledge regarding the benefits associated with home-based exercise programs.To determine whether home-based exercise programs improve functional capacity, health-related quality of life, muscle strength, and symptoms of depression among patients with stage III-V chronic kidney disease.A systematic review and meta-analyses following PRISMA guidelines were utilized. Relevant articles were collected and independently assessed for their inclusion eligibility. Effects of home-based exercise were summarized by the standardized mean differences and represented by forest plots (Review Manager 5.4).Eight studies were included, none of which reported any adverse effects. The intervention was usually aerobic, 76% of these programs lasted 3-6 months, and exercise adherence was 60-87.5%. Four studies measured health-related quality of life and found significant improvements in several subscales. Regarding functional capacity, five studies used the six-minute walking test (44.9 meters; 95% CI [30.45, 59.30]; p ≤ .001), three studies used the sit-to-stand-to-sit test (-0.45 seconds; 95% CI [-0.46, -0.26]; p ≤ .001), and two studies used the timed up-and-go test (-0.76 seconds; 95% CI [-1.38, -0.15]; p ≤ .001) and the handgrip strength test (1.16 kg; 95% CI [-2.88, 5.20]; p ≤ .001).Home-based exercise programs are beneficial to renal patients. These interventions are safe and effective to improve health-related quality of life and functional capacity and reduce symptoms of depression among patients with chronic kidney disease.

Published
2022

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