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1. The bii4africa dataset of faunal and floral population intactness estimates across Africas major land uses.

Author

Clements, Hayley, Do Linh San, Emmanuel, Hempson, Gareth, Linden, Birthe, Maritz, Bryan, Monadjem, Ara, Reynolds, Chevonne, Siebert, Frances, Stevens, Nicola, Biggs, Reinette, De Vos, Alta, Blanchard, Ryan, Child, Matthew, Esler, Karen, Hamann, Maike, Loft, Ty, Reyers, Belinda, Selomane, Odirilwe, Skowno, Andrew, Tshoke, Tshegofatso, Abdoulaye, Diarrassouba, Aebischer, Thierry, Aguirre-Gutiérrez, Jesús, Alexander, Graham, Ali, Abdullahi, Allan, David, Amoako, Esther, Angedakin, Samuel, Aruna, Edward, Avenant, Nico, Badjedjea, Gabriel, Bakayoko, Adama, Bamba-Kaya, Abraham, Bates, Michael, Bates, Paul, Belmain, Steven, Bennitt, Emily, Bradley, James, Brewster, Chris, Brown, Michael, Bryja, Josef, Butynski, Thomas, Carvalho, Filipe, Channing, Alan, Chapman, Colin, Cohen, Callan, Cords, Marina, Cramer, Jennifer, Cronk, Nadine, Cunneyworth, Pamela, Dalerum, Fredrik, Danquah, Emmanuel, Davies-Mostert, Harriet, de Blocq, Andrew, De Jong, Yvonne, Demos, Terrence, Denys, Christiane, Djagoun, Chabi, Doherty-Bone, Thomas, Drouilly, Marine, du Toit, Johan, Ehlers Smith, David, Ehlers Smith, Yvette, Eiseb, Seth, Fashing, Peter, Ferguson, Adam, Fernández-García, José, Finckh, Manfred, Fischer, Claude, Gandiwa, Edson, Gaubert, Philippe, Gaugris, Jerome, Gibbs, Dalton, Gilchrist, Jason, Gil-Sánchez, Jose, Githitho, Anthony, Goodman, Peter, Granjon, Laurent, Grobler, J, Gumbi, Bonginkosi, Gvozdik, Vaclav, Harvey, James, Hauptfleisch, Morgan, Hayder, Firas, Hema, Emmanuel, Herbst, Marna, Houngbédji, Mariano, Huntley, Brian, Hutterer, Rainer, Ivande, Samuel, Jackson, Kate, Jongsma, Gregory, Juste, Javier, Kadjo, Blaise, Kaleme, Prince, Kamugisha, Edwin, Kaplin, Beth, Kato, Humphrey, Kiffner, Christian, and Kimuyu, Duncan

Subjects
Animals, Humans, Ecosystem, Conservation of Natural Resources, Biodiversity, Vertebrates, Mammals
Abstract

Sub-Saharan Africa is under-represented in global biodiversity datasets, particularly regarding the impact of land use on species population abundances. Drawing on recent advances in expert elicitation to ensure data consistency, 200 experts were convened using a modified-Delphi process to estimate intactness scores: the remaining proportion of an intact reference population of a species group in a particular land use, on a scale from 0 (no remaining individuals) to 1 (same abundance as the reference) and, in rare cases, to 2 (populations that thrive in human-modified landscapes). The resulting bii4africa dataset contains intactness scores representing terrestrial vertebrates (tetrapods: ±5,400 amphibians, reptiles, birds, mammals) and vascular plants (±45,000 forbs, graminoids, trees, shrubs) in sub-Saharan Africa across the regions major land uses (urban, cropland, rangeland, plantation, protected, etc.) and intensities (e.g., large-scale vs smallholder cropland). This dataset was co-produced as part of the Biodiversity Intactness Index for Africa Project. Additional uses include assessing ecosystem condition; rectifying geographic/taxonomic biases in global biodiversity indicators and maps; and informing the Red List of Ecosystems.

Published
2024

2. TAD evolutionary and functional characterization reveals diversity in mammalian TAD boundary properties and function.

Author

Okhovat, Mariam, VanCampen, Jake, Nevonen, Kimberly, Harshman, Lana, Li, Weiyu, Layman, Cora, Ward, Samantha, Herrera, Jarod, Wells, Jackson, Sheng, Rory, Mao, Yafei, Ndjamen, Blaise, Lima, Ana, Vigh-Conrad, Katinka, Stendahl, Alexandra, Yang, Ran, Fedorov, Lev, Matthews, Ian, Easow, Sarah, Chan, Dylan, Jan, Taha, Eichler, Evan, Rugonyi, Sandra, Conrad, Donald, Carbone, Lucia, and Ahituv, Nadav

Subjects
Animals, Mice, Humans, Genomics, Genome, Gene Expression Regulation, Epigenomics, Chromatin Immunoprecipitation Sequencing, Chromatin, Mammals
Abstract

Topological associating domains (TADs) are self-interacting genomic units crucial for shaping gene regulation patterns. Despite their importance, the extent of their evolutionary conservation and its functional implications remain largely unknown. In this study, we generate Hi-C and ChIP-seq data and compare TAD organization across four primate and four rodent species and characterize the genetic and epigenetic properties of TAD boundaries in correspondence to their evolutionary conservation. We find 14% of all human TAD boundaries to be shared among all eight species (ultraconserved), while 15% are human-specific. Ultraconserved TAD boundaries have stronger insulation strength, CTCF binding, and enrichment of older retrotransposons compared to species-specific boundaries. CRISPR-Cas9 knockouts of an ultraconserved boundary in a mouse model lead to tissue-specific gene expression changes and morphological phenotypes. Deletion of a human-specific boundary near the autism-related AUTS2 gene results in the upregulation of this gene in neurons. Overall, our study provides pertinent TAD boundary evolutionary conservation annotations and showcases the functional importance of TAD evolution.

Published
2023

3. Defining Longer-Term Outcomes in an Ovine Model of Moderate Perinatal Hypoxia-Ischemia.

Author

Mike, Jana Krystofova, Wu, Katherine Y, White, Yasmine, Pathipati, Praneeti, Ndjamen, Blaise, Hutchings, Rachel S, Losser, Courtney, Vento, Christian, Arellano, Kimberly, Vanhatalo, Oona, Ostrin, Samuel, Windsor, Christine, Ha, Janica, Alhassen, Ziad, Goudy, Brian D, Vali, Payam, Lakshminrusimha, Satyan, Gobburu, Jogarao VS, Long-Boyle, Janel, Chen, Peggy, Wu, Yvonne W, Fineman, Jeffrey R, Ferriero, Donna M, and Maltepe, Emin

Subjects
Paediatrics, Biomedical and Clinical Sciences, Childhood Injury, Cerebral Palsy, Physical Injury - Accidents and Adverse Effects, Pediatric, Perinatal Period - Conditions Originating in Perinatal Period, Cerebrovascular, Brain Disorders, Preterm, Low Birth Weight and Health of the Newborn, Stroke, Unintentional Childhood Injury, Neurosciences, 2.1 Biological and endogenous factors, Neurological, Good Health and Well Being, Animals, Biomarkers, Brain, Female, Gliosis, Humans, Hypoxia-Ischemia, Brain, Infant, Inflammation, Ischemia, Pregnancy, Sheep, Brain hypoxia-ischemia, Neurodevelopmental outcomes, Ovine model, Neonates, Paediatrics and Reproductive Medicine, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences, Biological psychology
Abstract

Hypoxic-ischemic encephalopathy (HIE) is the leading cause of neonatal morbidity and mortality worldwide. Approximately 1 million infants born with HIE each year survive with cerebral palsy and/or serious cognitive disabilities. While infants born with mild and severe HIE frequently result in predictable outcomes, infants born with moderate HIE exhibit variable outcomes that are highly unpredictable. Here, we describe an umbilical cord occlusion (UCO) model of moderate HIE with a 6-day follow-up. Near-term lambs (n = 27) were resuscitated after the induction of 5 min of asystole. Following recovery, lambs were assessed to define neurodevelopmental outcomes. At the end of this period, lambs were euthanized, and brains were harvested for histological analysis. Compared with prior models that typically follow lambs for 3 days, the observation of neurobehavioral outcomes for 6 days enabled identification of animals that recover significant neurological function. Approximately 35% of lambs exhibited severe motor deficits throughout the entirety of the 6-day course and, in the most severely affected lambs, developed spastic diparesis similar to that observed in infants who survive severe neonatal HIE (severe, UCOs). Importantly, and similar to outcomes in human neonates, while initially developing significant acidosis and encephalopathy, the remainder of the lambs in this model recovered normal motor activity and exhibited normal neurodevelopmental outcomes by 6 days of life (improved, UCOi). The UCOs group exhibited gliosis and inflammation in both white and gray matters, oligodendrocyte loss, neuronal loss, and cellular death in the hippocampus and cingulate cortex. While the UCOi group exhibited more cellular death and gliosis in the parasagittal cortex, they demonstrated more preserved white matter markers, along with reduced markers of inflammation and lower cellular death and neuronal loss in Ca3 of the hippocampus compared with UCOs lambs. Our large animal model of moderate HIE with prolonged follow-up will help further define pathophysiologic drivers of brain injury while enabling identification of predictive biomarkers that correlate with disease outcomes and ultimately help support development of therapeutic approaches to this challenging clinical scenario.

Published
2022

4. Identification of a therapeutic interfering particle—A single-dose SARS-CoV-2 antiviral intervention with a high barrier to resistance

Author

Chaturvedi, Sonali, Vasen, Gustavo, Pablo, Michael, Chen, Xinyue, Beutler, Nathan, Kumar, Arjun, Tanner, Elizabeth, Illouz, Sylvia, Rahgoshay, Donna, Burnett, John, Holguin, Leo, Chen, Pei-Yi, Ndjamen, Blaise, Ott, Melanie, Rodick, Robert, Rogers, Thomas, Smith, Davey M, and Weinberger, Leor S

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Biological Sciences, Coronaviruses, Infectious Diseases, Biodefense, Lung, Emerging Infectious Diseases, Good Health and Well Being, Animals, Antiviral Agents, COVID-19, Cell Line, Chlorocebus aethiops, Culture Media, Conditioned, Defective Interfering Viruses, Drug Delivery Systems, Epithelial Cells, Humans, Male, Mesocricetus, Nanoparticles, SARS-CoV-2, Vero Cells, Virus Replication, COVID-19 Drug Treatment, RNA, coronavirus, defective interfering particles, evolution, intranasal, lipid nanoparticle, therapeutic interfering particles, variants, virus-like particle, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Viral-deletion mutants that conditionally replicate and inhibit the wild-type virus (i.e., defective interfering particles, DIPs) have long been proposed as single-administration interventions with high genetic barriers to resistance. However, theories predict that robust, therapeutic DIPs (i.e., therapeutic interfering particles, TIPs) must conditionally spread between cells with R0 >1. Here, we report engineering of TIPs that conditionally replicate with SARS-CoV-2, exhibit R0 >1, and inhibit viral replication 10- to 100-fold. Inhibition occurs via competition for viral replication machinery, and a single administration of TIP RNA inhibits SARS-CoV-2 sustainably in continuous cultures. Strikingly, TIPs maintain efficacy against neutralization-resistant variants (e.g., B.1.351). In hamsters, both prophylactic and therapeutic intranasal administration of lipid-nanoparticle TIPs durably suppressed SARS-CoV-2 by 100-fold in the lungs, reduced pro-inflammatory cytokine expression, and prevented severe pulmonary edema. These data provide proof of concept for a class of single-administration antivirals that may circumvent current requirements to continually update medical countermeasures against new variants.

Published
2021

5. Essential Emergency and Critical Care: a consensus among global clinical experts

Author

Schell, Carl Otto, Khalid, Karima, Wharton-Smith, Alexandra, Oliwa, Jacquie, Sawe, Hendry R, Roy, Nobhojit, Sanga, Alex, Marshall, John C, Rylance, Jamie, Hanson, Claudia, Kayambankadzanja, Raphael K, Wallis, Lee A, Jirwe, Maria, Baker, Tim, Asghar, Adam, Laytin, Adam D, Holloway, Adrian J, Adib, Ahmed Rhassane El, Michaelides, Alexia, Munoz, Alvaro Coronado, Muzuka, Amos, Fernández, Analía, Pembe, Andrea B, Wellhagen, Andreas, Smith, Andrew G, Gadgil, Anita, Hvarfner, Anna, Abayadeera, Anuja, Agulnik, Asya, Godard, Aurélie, Venkatesh, Balasubramanian, Yousif, Bargo Mahamat, Morton, Bhakti Sarang Ben, Kumar, Bharath, Vijayaraghavan, Tirupakuzhi, King, Bobby, Rice, Brian, Thwaites, C Louise, Tai, Chian Wern, Owoo, Christian, Sendagire, Cornelius, Petersen, Dan Brun, Tatay, Daniel, Skinner, David Lee, Kinyua, Denis, Ghosh, Dhruva, Aryal, Diptesh, Mlombwa, Donald, Thi, Duyen, Bui, Hanh, Lugazia, Edwin R, Riviello, Elisabeth, Molyneux, Elizabeth M, Heyns, Ellena, Nsutebu, Emmanuel Fru, Montalvo, Erika, Moreno, Ernesto Gerardo, Kanyangira, Esther Banda, Muttalib, Fiona, Mupeta, Francis, Diaz, Franco, Bulamba, Fred, Nzanzu, Furaha, Pascal, Blaise, Wooldridge, Gavin, Mwakisambwe, Gibonce, Richards, Guy A, Ammar, Hala, Mangat, Halinder S, Ghali, Hasanein H, Shah, Hiral A, Shum, Hoi Ping, Abdullahi, Ibrahim Salim, Martin-Loeches, Ignacio, von der Osten, Ingrid T, Mcknight, Jacob, Lee, James S, Namagga, Jane Kasozi, Eriksen, Jaran, Armour-Marshall, Jasmine, Kellett, John, Metcalfe, John Z, Moore, Jolene, Blixt, Jonas, Langton, Josephine, Mejia, Juan Gutierrez, Silesky-Jiménez, Juan Ignacio, Soni, Kapil Dev, Kohne, Karl Martin, Rowan, Kathryn, Yokobatake, Kazuhiro, Doi, Kent, Rudd, Kristina E, Akuamoah-Boateng, Kwame Asante, Irestedt, Lars, Losonczy, Lia I, Zhang, Lina, Kurland, Lisa, Guinness, Lorna, and Bains, Lovenish

Subjects
Health Services and Systems, Health Sciences, Health Services, Clinical Research, Emergency Care, Generic health relevance, Good Health and Well Being, COVID-19, Consensus, Critical Care, Emergency Medical Services, Humans, SARS-CoV-2, EECC Collaborators, EECC Collaborators*, health policy, health services research, health systems, surgery, Health services and systems, Public health
Abstract

BackgroundGlobally, critical illness results in millions of deaths every year. Although many of these deaths are potentially preventable, the basic, life-saving care of critically ill patients are often overlooked in health systems. Essential Emergency and Critical Care (EECC) has been devised as the care that should be provided to all critically ill patients in all hospitals in the world. EECC includes the effective care of low cost and low complexity for the identification and treatment of critically ill patients across all medical specialties. This study aimed to specify the content of EECC and additionally, given the surge of critical illness in the ongoing pandemic, the essential diagnosis-specific care for critically ill patients with COVID-19.MethodsIn a Delphi process, consensus (>90% agreement) was sought from a diverse panel of global clinical experts. The panel iteratively rated proposed treatments and actions based on previous guidelines and the WHO/ICRC's Basic Emergency Care. The output from the Delphi was adapted iteratively with specialist reviewers into a coherent and feasible package of clinical processes plus a list of hospital readiness requirements.ResultsThe 269 experts in the Delphi panel had clinical experience in different acute medical specialties from 59 countries and from all resource settings. The agreed EECC package contains 40 clinical processes and 67 requirements, plus additions specific for COVID-19.ConclusionThe study has specified the content of care that should be provided to all critically ill patients. Implementing EECC could be an effective strategy for policy makers to reduce preventable deaths worldwide.

Published
2021

6. The WOVEN trial: Wingspan One-year Vascular Events and Neurologic Outcomes

Author

Alexander, Michael J, Zauner, Alois, Gupta, Rishi, Alshekhlee, Amer, Fraser, Justin F, Toth, Gabor, Given, Curtis, Mackenzie, Larami, Kott, Brian, Hassan, Ameer E, Shownkeen, Harish, Baxter, Blaise W, Callison, R Charles, and Yu, Wengui

Subjects
Neurosciences, Clinical Research, Brain Disorders, Clinical Trials and Supportive Activities, Stroke, Aged, Cohort Studies, Constriction, Pathologic, Female, Follow-Up Studies, Humans, Intracranial Arteriosclerosis, Male, Middle Aged, Mortality, Nervous System Diseases, Stents, Treatment Outcome, stent, stenosis, atherosclerosis, intervention, stroke
Abstract

BackgroundPrior studies evaluating the Wingspan stent for treatment of symptomatic intracranial atherosclerotic disease have included patients with a spectrum of both on-label and off-label indications for the stent. The WEAVE trial assessed 152 patients stented with the Wingspan stent strictly by its current on-label indication and found a 2.6% periprocedural stroke and death rate.ObjectiveThis WOVEN study assesses the 1-year follow-up from this cohort.MethodsTwelve of the original 24 sites enrolling patients in the WEAVE trial performed follow-up chart review and imaging analysis up to 1 year after stenting. Assessment of delayed stroke and death was made in 129 patients, as well as vascular imaging follow-up to assess for in-stent re-stenosis.ResultsIn the 1-year follow-up period, seven patients had a stroke (six minor, one major). Subsequent to the periprocedural period, no deaths were recorded in the cohort. Including the four patients who had periprocedural events in the WEAVE study, there were 11 strokes or deaths of the 129 patients (8.5%) at the 1-year follow-up.ConclusionsThe WOVEN study provides the 1-year follow-up on a cohort of 129 patients who were stented according to the current on-label use. It provides a more homogeneous patient group for analysis than prior studies, and demonstrates a relatively low 8.5% 1-year stroke and death rate in stented patients.

Published
2021

7. Slum Health: Arresting COVID-19 and Improving Well-Being in Urban Informal Settlements

Author

Corburn, Jason, Vlahov, David, Mberu, Blessing, Riley, Lee, Caiaffa, Waleska Teixeira, Rashid, Sabina Faiz, Ko, Albert, Patel, Sheela, Jukur, Smurti, Martínez-Herrera, Eliana, Jayasinghe, Saroj, Agarwal, Siddharth, Nguendo-Yongsi, Blaise, Weru, Jane, Ouma, Smith, Edmundo, Katia, Oni, Tolu, and Ayad, Hany

Subjects
Behavioral and Social Science, Prevention, Infectious Diseases, Infection, Good Health and Well Being, Sustainable Cities and Communities, Clean Water and Sanitation, Betacoronavirus, COVID-19, Coronavirus Infections, Health Services Accessibility, Housing, Humans, Pandemics, Pneumonia, Viral, Poverty Areas, SARS-CoV-2, Sanitation, Urban Health, Urban Population, Vulnerable Populations, Slums, Informal settlements, Equity, Coronavirus, Community health, Global health, Human Movement and Sports Sciences, Public Health and Health Services, Public Health
Abstract

The informal settlements of the Global South are the least prepared for the pandemic of COVID-19 since basic needs such as water, toilets, sewers, drainage, waste collection, and secure and adequate housing are already in short supply or non-existent. Further, space constraints, violence, and overcrowding in slums make physical distancing and self-quarantine impractical, and the rapid spread of an infection highly likely. Residents of informal settlements are also economically vulnerable during any COVID-19 responses. Any responses to COVID-19 that do not recognize these realities will further jeopardize the survival of large segments of the urban population globally. Most top-down strategies to arrest an infectious disease will likely ignore the often-robust social groups and knowledge that already exist in many slums. Here, we offer a set of practice and policy suggestions that aim to (1) dampen the spread of COVID-19 based on the latest available science, (2) improve the likelihood of medical care for the urban poor whether or not they get infected, and (3) provide economic, social, and physical improvements and protections to the urban poor, including migrants, slum communities, and their residents, that can improve their long-term well-being. Immediate measures to protect residents of urban informal settlements, the homeless, those living in precarious settlements, and the entire population from COVID-19 include the following: (1) institute informal settlements/slum emergency planning committees in every urban informal settlement; (2) apply an immediate moratorium on evictions; (3) provide an immediate guarantee of payments to the poor; (4) immediately train and deploy community health workers; (5) immediately meet Sphere Humanitarian standards for water, sanitation, and hygiene; (6) provide immediate food assistance; (7) develop and implement a solid waste collection strategy; and (8) implement immediately a plan for mobility and health care. Lessons have been learned from earlier pandemics such as HIV and epidemics such as Ebola. They can be applied here. At the same time, the opportunity exists for public health, public administration, international aid, NGOs, and community groups to innovate beyond disaster response and move toward long-term plans.

Published
2020

8. Clinical applications of donor lymphocyte infusion from an HLA-haploidentical donor: consensus recommendations from the Acute Leukemia Working Party of the EBMT

Author

Dholaria, Bhagirathbhai, Savani, Bipin N, Labopin, Myriam, Luznik, Leo, Ruggeri, Annalisa, Mielke, Stephan, Malki, Monzr M Al, Kongtim, Piyanuch, Fuchs, Ephraim, Huang, Xiao-Jun, Locatelli, Franco, Aversa, Franco, Castagna, Luca, Bacigalupo, Andrea, Martelli, Massimo, Blaise, Didier, Soussan, Patrick Ben, Arnault, Yolande, Handgretinger, Rupert, Roy, Denis-Claude, O’Donnell, Paul, Bashey, Asad, Solomon, Scott, Romee, Rizwan, Lewalle, Philippe, Gayoso, Jorge, Maschan, Michael, Lazarus, Hillard M, Ballen, Karen, Giebel, Sebastian, Baron, Frederic, Ciceri, Fabio, Esteve, Jordi, Gorin, Norbert-Claude, Spyridonidis, Alexandros, Schmid, Christoph, Ciurea, Stefan O, Nagler, Arnon, and Mohty, Mohamad

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Immunology, Transplantation, Cancer, Regenerative Medicine, Rare Diseases, Prevention, Hematology, Stem Cell Research, Inflammatory and immune system, Consensus, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Humans, Lymphocytes, Prospective Studies, Retrospective Studies, Cardiorespiratory Medicine and Haematology, Cardiovascular medicine and haematology
Abstract

Donor lymphocyte infusion has been used in the management of relapsed hematologic malignancies after allogeneic hematopoietic cell transplantation. It can eradicate minimal residual disease or be used to rescue a hematologic relapse, being able to induce durable remissions in a subset of patients. With the increased use of haploidentical hematopoietic cell transplantation, there is renewed interest in the use of donor lymphocytes to either treat or prevent disease relapse post transplant. Published retrospective and small prospective studies have shown encouraging results with therapeutic donor lymphocyte infusion in different haploidentical transplantation platforms. In this consensus paper, finalized on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, we summarize the available evidence on the use of donor lymphocyte infusion from haploidentical donor, and provide recommendations on its therapeutic, pre-emptive and prophylactic use in clinical practice.

Published
2020

9. Single-Cell Transcriptomics in Medulloblastoma Reveals Tumor-Initiating Progenitors and Oncogenic Cascades during Tumorigenesis and Relapse

Author

Zhang, Liguo, He, Xuelian, Liu, Xuezhao, Zhang, Feng, Huang, L Frank, Potter, Andrew S, Xu, Lingli, Zhou, Wenhao, Zheng, Tao, Luo, Zaili, Berry, Kalen P, Pribnow, Allison, Smith, Stephanie M, Fuller, Christine, Jones, Blaise V, Fouladi, Maryam, Drissi, Rachid, Yang, Zeng-Jie, Gustafson, W Clay, Remke, Marc, Pomeroy, Scott L, Girard, Emily J, Olson, James M, Morrissy, A Sorana, Vladoiu, Maria C, Zhang, Jiao, Tian, Weidong, Xin, Mei, Taylor, Michael D, Potter, S Steven, Roussel, Martine F, Weiss, William A, and Lu, Q Richard

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Cancer, Stem Cell Research, Rare Diseases, Brain Cancer, Stem Cell Research - Nonembryonic - Non-Human, Stem Cell Research - Nonembryonic - Human, Human Genome, Biotechnology, Neurosciences, Pediatric, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Animals, Brain Neoplasms, Cell Line, Tumor, Cell Proliferation, Cell Transformation, Neoplastic, Child, Preschool, Datasets as Topic, Disease Models, Animal, Female, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, Gene Regulatory Networks, Hedgehog Proteins, Humans, Male, Medulloblastoma, Mice, Transgenic, Neoplasm Recurrence, Local, Neoplastic Stem Cells, Neuroglia, Oligodendrocyte Transcription Factor 2, Prognosis, RNA-Seq, Signal Transduction, Single-Cell Analysis, Survival Analysis, Transcriptome, AURORA-A/MYCN, HIPPO-YAP/TAZ, OLIG2, OPC-like, glial progenitors, medulloblastomas, progenitor heterogeneity, recurrent tumors, single-cell transcriptomics, sonic hedgehog (SHH) signaling, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Progenitor heterogeneity and identities underlying tumor initiation and relapse in medulloblastomas remain elusive. Utilizing single-cell transcriptomic analysis, we demonstrated a developmental hierarchy of progenitor pools in Sonic Hedgehog (SHH) medulloblastomas, and identified OLIG2-expressing glial progenitors as transit-amplifying cells at the tumorigenic onset. Although OLIG2+ progenitors become quiescent stem-like cells in full-blown tumors, they are highly enriched in therapy-resistant and recurrent medulloblastomas. Depletion of mitotic Olig2+ progenitors or Olig2 ablation impeded tumor initiation. Genomic profiling revealed that OLIG2 modulates chromatin landscapes and activates oncogenic networks including HIPPO-YAP/TAZ and AURORA-A/MYCN pathways. Co-targeting these oncogenic pathways induced tumor growth arrest. Together, our results indicate that glial lineage-associated OLIG2+ progenitors are tumor-initiating cells during medulloblastoma tumorigenesis and relapse, suggesting OLIG2-driven oncogenic networks as potential therapeutic targets.

Published
2019

10. WEAVE Trial

Author

Alexander, Michael J, Zauner, Alois, Chaloupka, John C, Baxter, Blaise, Callison, Richard C, Gupta, Rishi, Song, Shlee S, Yu, Wengui, Feng, Lei, Bonovich, David, Toth, Gabor, Kott, Brian, Veznedaroglu, Erol, Ringer, Andrew, Meyers, Philip, Agola, John, Ghodke, Basavaraj, Alhajeri, Abdulnasser, Fraser, Justin, Given, Curtis, de Valle, Eric Lopez, Shah, Qaisar, Nesbit, Gary, Hassan, Ameer, Grobelny, Thomas, Fessler, Richard, and Shownkeen, Harish

Subjects
Brain Disorders, Clinical Trials and Supportive Activities, Cardiovascular, Clinical Research, Stroke, Neurosciences, Atherosclerosis, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Aged, Angioplasty, Female, Humans, Intracranial Arteriosclerosis, Intraoperative Complications, Male, Middle Aged, Prospective Studies, Stents, Treatment Outcome, angioplasty, antiplatelet therapy, atherosclerosis, patient selection, stents, WEAVE Trial Sites and Interventionalists, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Neurology & Neurosurgery
Abstract

Background and Purpose- The WEAVE trial (Wingspan Stent System Post Market Surveillance) is a postmarket surveillance trial mandated by the Food and Drug Administration to assess the periprocedural safety of the Wingspan Stent system in the treatment of symptomatic intracranial atherosclerotic disease. Methods- A total of 152 consecutive patients who met the Food and Drug Administration on-label usage criteria were enrolled at 24 hospitals and underwent angioplasty and stenting with the Wingspan stent. On-label criteria included age 22 to 80 years, symptomatic intracranial atherosclerotic stenosis of 70% to 99%, baseline modified Rankin Scale score ≤3, ≥2 strokes in the vascular territory of the stenotic lesion with at least 1 stroke while on medical therapy, and stenting of the lesion ≥8 days after the last stroke. The primary analysis assessed the periprocedural stroke, bleed, and death rate within 72 hours of the procedure with adjudication by a core study Stroke Neurologist. Results- The trial was stopped early after interim analysis of 152 consecutive patients demonstrated a lower than expected 2.6% (4/152 patients) periprocedural stroke, bleed, and death rate. This was lower than the 4% periprocedural primary event safety benchmark set for the interim analysis in the study. A total of 97.4% (148/152) patients were event-free at 72 hours, 1.3% (2/152) had nonfatal strokes, and 1.3% (2/152) of patients died. Conclusions- With experienced interventionalists, and proper patient selection following the on-label usage guidelines, the use of the Wingspan stent for intracranial atherosclerotic disease demonstrated a low periprocedural complication rate and excellent safety profile. This is the largest on-label, multicenter, prospective trial of the Wingspan stent system to date with the lowest reported complication rate. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02034058.

Published
2019

11. WEAVE Trial: Final Results in 152 On-Label Patients.

Author

Alexander, Michael J, Zauner, Alois, Chaloupka, John C, Baxter, Blaise, Callison, Richard C, Gupta, Rishi, Song, Shlee S, Yu, Wengui, and WEAVE Trial Sites and Interventionalists

Subjects
WEAVE Trial Sites and Interventionalists, Humans, Intracranial Arteriosclerosis, Intraoperative Complications, Treatment Outcome, Angioplasty, Prospective Studies, Stents, Aged, Middle Aged, Female, Male, angioplasty, antiplatelet therapy, atherosclerosis, patient selection, stents, Neurology & Neurosurgery, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Neurosciences
Abstract

Background and Purpose- The WEAVE trial (Wingspan Stent System Post Market Surveillance) is a postmarket surveillance trial mandated by the Food and Drug Administration to assess the periprocedural safety of the Wingspan Stent system in the treatment of symptomatic intracranial atherosclerotic disease. Methods- A total of 152 consecutive patients who met the Food and Drug Administration on-label usage criteria were enrolled at 24 hospitals and underwent angioplasty and stenting with the Wingspan stent. On-label criteria included age 22 to 80 years, symptomatic intracranial atherosclerotic stenosis of 70% to 99%, baseline modified Rankin Scale score ≤3, ≥2 strokes in the vascular territory of the stenotic lesion with at least 1 stroke while on medical therapy, and stenting of the lesion ≥8 days after the last stroke. The primary analysis assessed the periprocedural stroke, bleed, and death rate within 72 hours of the procedure with adjudication by a core study Stroke Neurologist. Results- The trial was stopped early after interim analysis of 152 consecutive patients demonstrated a lower than expected 2.6% (4/152 patients) periprocedural stroke, bleed, and death rate. This was lower than the 4% periprocedural primary event safety benchmark set for the interim analysis in the study. A total of 97.4% (148/152) patients were event-free at 72 hours, 1.3% (2/152) had nonfatal strokes, and 1.3% (2/152) of patients died. Conclusions- With experienced interventionalists, and proper patient selection following the on-label usage guidelines, the use of the Wingspan stent for intracranial atherosclerotic disease demonstrated a low periprocedural complication rate and excellent safety profile. This is the largest on-label, multicenter, prospective trial of the Wingspan stent system to date with the lowest reported complication rate. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02034058.

Published
2019

12. PTCy-based haploidentical vs matched related or unrelated donor reduced-intensity conditioning transplant for DLBCL.

Author

Dreger, Peter, Sureda, Anna, Ahn, Kwang, Eapen, Mary, Litovich, Carlos, Finel, Herve, Boumendil, Ariane, Gopal, Ajay, Herrera, Alex, Schmid, Christoph, Diez-Martin, José, Fuchs, Ephraim, Bolaños-Meade, Javier, Gooptu, Mahasweta, Al Malki, Monzr, Castagna, Luca, Ciurea, Stefan, Dominietto, Alida, Blaise, Didier, Ciceri, Fabio, Tischer, Johanna, Corradini, Paolo, Montoto, Silvia, Robinson, Stephen, Gülbas, Zafer, and Hamadani, Mehdi

Subjects
Adult, Aged, Female, Hematopoietic Stem Cell Transplantation, Humans, Lymphoma, Large B-Cell, Diffuse, Male, Middle Aged, Retrospective Studies, Tissue Donors, Transplantation Conditioning, Young Adult
Abstract

This study retrospectively compared long-term outcomes of nonmyeloablative/reduced intensity conditioning (NMC/RIC) allogeneic hematopoietic cell transplantation (allo-HCT) from a haploidentical family donor (haplo-HCT) using posttransplant cyclophosphamide (PTCy) with those of matched sibling donor (MSD) and matched unrelated donor (MUD) with or without T-cell depletion (TCD+/TCD-) in patients with relapsed diffuse large B-cell lymphoma (DLBCL). Adult patients with DLBCL who had undergone their first NMC/RIC allo-HCT between 2008 and 2015 were included. Recipients of haplo-HCT were limited to those receiving graft-versus-host disease (GVHD) prophylaxis with PTCy. GVHD prophylaxis in MSD was limited to calcineurin inhibitor (CNI)-based approaches without in vivo TCD, while MUD recipients received CNI-based prophylaxis with or without TCD. Outcome analyses for overall survival (OS) and progression-free survival (PFS), nonrelapse mortality (NRM), and disease relapse/progression were calculated. A total of 1438 patients (haplo, 132; MSD, 525; MUD TCD+, 403; and MUD TCD-, 378) were included. Patients with haplo donors were significantly older, had a better performance status and had more frequently received total body irradiation-based conditioning regimens and bone marrow grafts than MSD and MUD TCD+ or TCD-. 3-year OS, PFS, NRM and relapse/progression incidence after haplo-HCT was 46%, 38%, 22%, and 41%, respectively, and not significantly different from outcomes of matched donor transplants on multivariate analyses. Haplo-HCT was associated with a lower cumulative incidence of chronic GVHD compared with MSD, MUD TCD+/TCD-. NMC/RIC haplo-HCT with PTCy seems to be a valuable alternative for patients with DLBCL considered for allo-HCT but lacking a matched donor.

Published
2019

13. Outcomes of Haploidentical Transplantation in Patients with Relapsed Multiple Myeloma: An EBMT/CIBMTR Report

Author

Sahebi, Firoozeh, Garderet, Laurent, Kanate, Abraham S, Eikema, Diderik-Jan, Knelange, Nina Simone, Alvelo, Omar F Dávila, Koc, Yener, Blaise, Didier, Bashir, Qaiser, Moraleda, José M, Dreger, Peter, Sanchez, James F, Ciurea, Stefan, Schouten, Harry, Shah, Nirav N, Verbeek, Mareike, Rösler, Wolf, Diez-Martin, Jose L, Schoenland, Stefan, D'Souza, Anita, Kröger, Nicolaus, and Hari, Parameswaran

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Regenerative Medicine, Stem Cell Research, Clinical Trials and Supportive Activities, Transplantation, Clinical Research, Hematology, Rare Diseases, Cancer, Good Health and Well Being, Adult, Aged, Allografts, Disease-Free Survival, Female, Follow-Up Studies, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Humans, Incidence, Male, Middle Aged, Multiple Myeloma, Recurrence, Retrospective Studies, Risk Factors, Survival Rate, Allogeneic hematopoietic cell transplantation, Haploidentical, Multiple myeloma, Clinical Sciences, Immunology, Cardiovascular medicine and haematology
Abstract

Allogeneic hematopoietic cell transplantation (allo-HCT) using siblings and matched donors has the potential for long-term disease control in a subset of high-risk patients with multiple myeloma (MM); however, the data on using haploidentical donors in this disease are limited. We conducted a retrospective analysis to examine the outcomes of patients with MM who underwent haploidentical allo-HCT within European Society for Blood and Marrow Transplantation/Center for International Blood and Marrow Transplant Research centers. A total of 96 patients underwent haploidentical allo-HCT between 2008 and 2016. With a median follow-up of 24.0 months (range, 13.2 to 24.9 months), 97% (95% confidence interval [CI], 93% to 100%) of patients had neutrophil engraftment by day 28, and 75% (95% CI, 66% to 84%) achieved platelet recovery by day 60. Two-year progression-free survival (PFS) was 17% (95% CI, 8% to 26%), and overall survival (OS) was 48% (95% CI, 36% to 59%). At 2 years, the cumulative risk of relapse/progression was 56% (95% CI, 45% to 67%), and 1-year nonrelapse mortality (NRM) was 21% (95% CI, 13% to 29%). The incidences of acute graft-versus-host-disease (GVHD) grades II-IV by 100 days and chronic GVHD at 2 years were 39% (95% CI, 28% to 49%) and 46% (95% CI, 34% to 59%), respectively. On univariate analysis, use of post-transplantation cyclophosphamide (PT-Cy) (54% [95% CI, 41% to 68%] versus 25% [95% CI, 1% to 48%]; P =.009) and use of bone marrow as source of stem cells (72% [95% CI, 55% to 89%] versus 31% [95% CI, 17% to 46%]; P = .001) were associated with improved OS at 2 years. Disease status, patient sex, intensity of conditioning regimen, recipient/donor sex mismatch, and cytomegalovirus serostatus had no impact on OS, PFS, or NRM. Haploidentical transplantation is feasible for patients with multiply relapsed or high-risk MM, with an encouraging 2-year OS of 48% and an NRM of 21% at 1 year, supporting further investigation of haploidentical allo-HCT in suitable candidates with MM.

Published
2019

14. Trevo 2000: Results of a Large Real-World Registry for Stent Retriever for Acute Ischemic Stroke.

Author

Binning, Mandy, Bartolini, Bruno, Baxter, Blaise, Budzik, Ronald, English, Joey, Gupta, Rishi, Hedayat, Hirad, Krajina, Antonin, Liebeskind, David, Nogueira, Raul, Shields, Ryan, and Veznedaroglu, Erol

Subjects
endovascular treatment, stroke, ischemic, thrombectomy, Aged, Aged, 80 and over, Brain Ischemia, Databases, Factual, Disability Evaluation, Endovascular Procedures, Female, Humans, Male, Middle Aged, Prospective Studies, Prosthesis Design, Recovery of Function, Registries, Risk Factors, Stents, Stroke, Thrombectomy, Time Factors, Treatment Outcome
Abstract

Background Recent randomized controlled trials show benefit of thrombectomy for large vessel occlusion in stroke. Real-world data aid in assessing reproducibility of outcomes outside of clinical trials. The Trevo Retriever Registry is a multicenter, international, prospective study designed to assess outcomes in a large cohort of patients. Methods and Results The Trevo Registry is a prospective database of patients with large vessel occlusion treated with the Trevo device as the first device. The primary end point is revascularization based on modified Thrombolysis in Cerebral Infarction score and secondary end points include 90-day modified Rankin Scale, 90-day mortality, neurological deterioration at 24 hours, and device/procedure related adverse events. Year 2008 patients were enrolled at 76 centers in 12 countries. Median admission National Institutes of Health Stroke Scale was 16 (interquartile range, 11-20). Occlusion sites were internal carotid artery (17.8%), middle cerebral artery (73.5%), posterior circulation (7.1%), and distal vascular locations (1.6%). A modified Thrombolysis in Cerebral Infarction 2b or 3 was achieved in 92.8% (95% CI, 91.6, 93.9) of procedures, with 55.3% (95% CI, 53.1, 57.5) of patients achieving modified Rankin Scale ≤2 at 3 months. Patients meeting revised 2015 American Heart Association criteria for thrombectomy had a 59.7% (95% CI , 56.0; 63.4) modified Rankin Scale 0 to 2 at 3 months, whereas 51.4% treated outside of American Heart Association criteria had modified Rankin Scale 0 to 2. 51.4% (95% CI , 49.6, 55.4). Symptomatic intracranial hemorrhage rate was 1.7% (95% CI , 1.2, 2.4). Conclusions The Trevo Retriever Registry represents real-world data with stent retriever. The registry demonstrates similar reperfusion rates and outcomes in the community compared with rigorous centrally adjudicated clinical trials. Future subgroup analysis of this cohort will assist in identifying areas of future research. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT 02040259.

Published
2018

15. Related donor transplants: has posttransplantation cyclophosphamide nullified the detrimental effect of HLA mismatch?

Author

Robinson, Tara, Fuchs, Ephraim, Zhang, Mei-Jie, St Martin, Andrew, Labopin, Myriam, Keesler, Daniel, Blaise, Didier, Bashey, Asad, Bourhis, Jean-Henri, Ciceri, Fabio, Ciurea, Stefan, Devine, Steven, Mohty, Mohamad, McCurdy, Shannon, Milpied, Noel, McNiece, Ian, Rocha, Vanderson, Romee, Rizwan, Socie, Gerard, Yakoub-Agha, Ibrahim, Soiffer, Robert, Eapen, Mary, and Nagler, Arnon

Subjects
Acute Disease, Adolescent, Adult, Aged, Chronic Disease, Cyclophosphamide, Disease-Free Survival, Female, Graft vs Host Disease, HLA Antigens, Hematopoietic Stem Cell Transplantation, Humans, Leukemia, Male, Middle Aged, Survival Rate, Tissue Donors
Abstract

We sought to identify whether posttransplantation cyclophosphamide (PT-Cy) reduces or eliminates the detrimental impact of HLA mismatching on outcomes of HLA-haploidentical related donor transplantation for acute leukemia. Data from 2143 donor-recipient pairs (n = 218 haploidentical sibling; n = 218 offspring; n = 1707 HLA-matched sibling) with acute myeloid or lymphoblastic leukemia were studied. All received a calcineurin inhibitor for graft-versus-host disease (GVHD) prophylaxis while high-dose PT-Cy was also given to recipients of haploidentical transplant. Patient age correlated with donor-recipient relationship: haploidentical siblings donated to patients aged 18 to 54 years whereas offspring donated to patients aged 55 to 76 years. Therefore, transplant outcomes were examined separately in the 2 patient age groups. In patients aged 18 to 54 years, there were no significant differences in outcomes except chronic GVHD, which was lower after haploidentical sibling compared to HLA-matched sibling transplant (hazard ratio [HR], 0.63; P < .001). In patients aged 55 to 76 years, despite lower chronic GVHD (HR, 0.42; P < .001), graft failure (14% vs 6%; P = .003), nonrelapse mortality (HR, 1.48; P = .02), and overall mortality (HR, 1.32; P = .003) were higher after transplant from offspring compared with an HLA-matched sibling. These data demonstrate a superior outcome in older recipients when using an HLA-matched sibling instead of offspring, although there were differences in transplant platforms (GVHD prophylaxis and graft type) between the 2 groups. Validation of these findings requires a prospective randomized trial wherein the transplant platforms can be closely matched.

Published
2018

16. The European Society for Blood and Marrow Transplantation (EBMT) Consensus Guidelines for the Detection and Treatment of Donor-specific Anti-HLA Antibodies (DSA) in Haploidentical Hematopoietic Cell Transplantation

Author

Ciurea, Stefan O, Cao, Kai, Fernandez-Vina, Marcelo, Kongtim, Piyanuch, Malki, Monzr Al, Fuchs, Ephraim, Luznik, Leo, Huang, Xiao-Jun, Ciceri, Fabio, Locatelli, Franco, Aversa, Franco, Castagna, Luca, Bacigalupo, Andrea, Martelli, Massimo, Blaise, Didier, Handgretinger, Rupert, Roy, Denis-Claude, O’Donnell, Paul, Bashey, Asad, Lazarus, Hillard M, Ballen, Karen, Savani, Bipin N, Mohty, Mohamad, and Nagler, Arnon

Subjects
Transplantation, Regenerative Medicine, Stem Cell Research, Organ Transplantation, Development of treatments and therapeutic interventions, 5.4 Surgery, Inflammatory and immune system, Bone Marrow Transplantation, Graft Rejection, HLA Antigens, Hematopoietic Stem Cell Transplantation, Humans, Isoantibodies, Tissue Donors, Transplantation, Haploidentical, Treatment Outcome, Clinical Sciences, Oncology and Carcinogenesis, Immunology
Abstract

Haploidentical donors are now increasingly considered for transplantation in the absence of HLA-matched donors or when an urgent transplant is needed. Donor-specific anti-HLA antibodies (DSA) have been recently recognized as an important barrier against successful engraftment of donor cells, which can affect transplant survival. DSA appear more prevalent in this type of transplant due to higher likelihood of alloimmunization of multiparous females against offspring's HLA antigens, and the degree of mismatch. Here we summarize the evidence for the role of DSA in the development of primary graft failure in haploidentical transplantation and provide consensus recommendations from the European Society for Blood and Marrow Transplant Group on testing, monitoring, and treatment of patients with DSA receiving haploidentical hematopoietic progenitor cell transplantation.

Published
2018

17. Interhospital Transfer Before Thrombectomy Is Associated With Delayed Treatment and Worse Outcome in the STRATIS Registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke)

Author

Froehler, Michael T, Saver, Jeffrey L, Zaidat, Osama O, Jahan, Reza, Aziz-Sultan, Mohammad Ali, Klucznik, Richard P, Haussen, Diogo C, Hellinger, Frank R, Yavagal, Dileep R, Yao, Tom L, Liebeskind, David S, Jadhav, Ashutosh P, Gupta, Rishi, Hassan, Ameer E, Martin, Coleman O, Bozorgchami, Hormozd, Kaushal, Ritesh, Nogueira, Raul G, Gandhi, Ravi H, Peterson, Eric C, Dashti, Shervin R, Given, Curtis A, Mehta, Brijesh P, Deshmukh, Vivek, Starkman, Sidney, Linfante, Italo, McPherson, Scott H, Kvamme, Peter, Grobelny, Thomas J, Hussain, Muhammad S, Thacker, Ike, Vora, Nirav, Chen, Peng Roc, Monteith, Stephen J, Ecker, Robert D, Schirmer, Clemens M, Sauvageau, Eric, Abou-Chebl, Alex, Derdeyn, Colin P, Maidan, Lucian, Badruddin, Aamir, Siddiqui, Adnan H, Dumont, Travis M, Alhajeri, Abdulnasser, Taqi, M Asif, Asi, Khaled, Carpenter, Jeffrey, Boulos, Alan, Jindal, Gaurav, Puri, Ajit S, Chitale, Rohan, Deshaies, Eric M, Robinson, David H, Kallmes, David F, Baxter, Blaise W, Jumaa, Mouhammad A, Sunenshine, Peter, Majjhoo, Aniel, English, Joey D, Suzuki, Shuichi, Fessler, Richard D, Almandoz, Josser E Delgado, Martin, Jerry C, and Mueller-Kronast, Nils H

Subjects
Stroke, Clinical Research, Brain Disorders, Endovascular Procedures, Hospitals, Humans, Ischemia, Patient Transfer, Prospective Studies, Registries, Survival Analysis, Thrombectomy, Time Factors, Treatment Outcome, emergency medical services, endovascular treatment, ischemic stroke, stent retriever, systems of care, STRATIS Investigators, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services, Cardiovascular System & Hematology
Abstract

BackgroundEndovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation.MethodsSTRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0-2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass.ResultsA total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients (P

Published
2017

18. Four ethical priorities for neurotechnologies and AI

Author

Yuste, Rafael, Goering, Sara, Arcas, Blaise Agüera Y, Bi, Guoqiang, Carmena, Jose M, Carter, Adrian, Fins, Joseph J, Friesen, Phoebe, Gallant, Jack, Huggins, Jane E, Illes, Judy, Kellmeyer, Philipp, Klein, Eran, Marblestone, Adam, Mitchell, Christine, Parens, Erik, Pham, Michelle, Rubel, Alan, Sadato, Norihiro, Sullivan, Laura Specker, Teicher, Mina, Wasserman, David, Wexler, Anna, Whittaker, Meredith, and Wolpaw, Jonathan

Subjects
Information and Computing Sciences, Human-Centred Computing, Philosophy and Religious Studies, Neurological, Alzheimer Disease, Animals, Artificial Intelligence, Bioengineering, Biomedical Enhancement, Brain-Computer Interfaces, Codes of Ethics, Electroencephalography, Female, Guidelines as Topic, Humans, Individuality, Informed Consent, Male, Neural Networks, Computer, Neurosciences, Parkinson Disease, Privacy, General Science & Technology
Abstract

Artificial intelligence and brain-computer interfaces must respect and preserve people’s privacy, identity, agency and equality, say Rafael Yuste, Sara Goering and colleagues.

Published
2017

19. A distinct innate lymphoid cell population regulates tumor-associated T cells

Author

Crome, Sarah Q, Nguyen, Linh T, Lopez-Verges, Sandra, Yang, SY Cindy, Martin, Bernard, Yam, Jennifer Y, Johnson, Dylan J, Nie, Jessica, Pniak, Michael, Yen, Pei Hua, Milea, Anca, Sowamber, Ramlogan, Katz, Sarah Rachel, Bernardini, Marcus Q, Clarke, Blaise A, Shaw, Patricia A, Lang, Philipp A, Berman, Hal K, Pugh, Trevor J, Lanier, Lewis L, and Ohashi, Pamela S

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Immunotherapy, Cancer, 2.1 Biological and endogenous factors, CD3 Complex, CD56 Antigen, Cell Proliferation, Cytokines, Flow Cytometry, Humans, Immune Tolerance, Immunity, Innate, Interleukins, Killer Cells, Natural, Lymphocytes, Lymphocytes, Tumor-Infiltrating, Natural Cytotoxicity Triggering Receptor 1, Neoplasms, T-Lymphocytes, Tumor Microenvironment, Interleukin-22, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract

Antitumor T cells are subject to multiple mechanisms of negative regulation. Recent findings that innate lymphoid cells (ILCs) regulate adaptive T cell responses led us to examine the regulatory potential of ILCs in the context of cancer. We identified a unique ILC population that inhibits tumor-infiltrating lymphocytes (TILs) from high-grade serous tumors, defined their suppressive capacity in vitro, and performed a comprehensive analysis of their phenotype. Notably, the presence of this CD56+CD3- population in TIL cultures was associated with reduced T cell numbers, and further functional studies demonstrated that this population suppressed TIL expansion and altered TIL cytokine production. Transcriptome analysis and phenotypic characterization determined that regulatory CD56+CD3- cells exhibit low cytotoxic activity, produce IL-22, and have an expression profile that overlaps with those of natural killer (NK) cells and other ILCs. NKp46 was highly expressed by these cells, and addition of anti-NKp46 antibodies to TIL cultures abrogated the ability of these regulatory ILCs to suppress T cell expansion. Notably, the presence of these regulatory ILCs in TIL cultures corresponded with a striking reduction in the time to disease recurrence. These studies demonstrate that a previously uncharacterized ILC population regulates the activity and expansion of tumor-associated T cells.

Published
2017

20. Proceedings from the Second Haploidentical Stem Cell Transplantation Symposium-Haplo2014, San Francisco, California, December 4, 2014.

Author

Al Malki, Monzr, Horowitz, Mary, Handgretinger, Rupert, Leung, Wing, Roy, Denis-Claude, Huang, Xiao-Jun, Fuchs, Ephraim, Locatelli, Franco, Blaise, Didier, Mineishi, Shin, Martelli, Massimo, Miller, Jeffrey, June, Carl, Ai, Hui-Sheng, Luznik, Leo, Mavilio, Domenico, Lugli, Enrico, van den Brink, Marcel, Champlin, Richard, and Ciurea, Stefan

Subjects
Cellular therapy, Haploidentical transplantation, Immunologic reconstitution after transplantation, Post-transplantation cyclophosphamide, T cell depleted, Animals, Antineoplastic Agents, Alkylating, Clinical Trials as Topic, Cyclophosphamide, Disease Models, Animal, Graft vs Host Disease, HLA Antigens, Hematologic Neoplasms, Histocompatibility Testing, Humans, Mice, Recurrence, San Francisco, Secondary Prevention, Stem Cell Transplantation, Survival Analysis, T-Lymphocytes, Regulatory, Transplantation, Isogeneic, Unrelated Donors
Abstract

Significant progress has been made over the past decade in haploidentical transplantation, with the development of novel methods to control intense alloreactive reactions generated in the major HLA-mismatched setting. Application of post-transplantation cyclophosphamide has gained worldwide acceptance as an effective and low-cost way to perform this type of transplantation, with outcomes now similar to those from HLA-matched unrelated donors. These advances have resulted in improved treatment-related mortality, whereas disease relapse has emerged as the most common cause of treatment failure. In addition, improvements in immunologic reconstitution after transplantation are much needed, not only in haploidentical transplantation but in all forms of stem cell transplantation. This symposium has focused on some of the most promising methods to control alloreactivity in this form of transplantation and application of cellular therapy to prevent disease relapse after transplantation, as well as understanding immunologic reconstitution and foreseeable approaches to improve immune recovery after transplantation.

Published
2016

21. Rapid learning curve for Solitaire FR stent retriever therapy: evidence from roll-in and randomised patients in the SWIFT trial

Author

Sheth, Sunil A, Jahan, Reza, Levy, Elad I, Jovin, Tudor G, Baxter, Blaise, Nogueira, Raul G, Clark, Wayne, Budzik, Ronald, Zaidat, Osama O, and Saver, Jeffrey L

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Cerebrovascular, Neurosciences, Bioengineering, Clinical Research, Brain Disorders, Stroke, Assistive Technology, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Aged, Aged, 80 and over, Brain Ischemia, Female, Humans, Learning Curve, Male, Middle Aged, Prospective Studies, Stents, Survival Rate, Thrombectomy, SWIFT Trialists, Angiography, Intervention, Technique, Clinical sciences
Abstract

BackgroundIn light of recent positive trial data for endovascular therapy in acute ischemic stroke (AIS), stent retriever use by practitioners without prior experience with these devices may become more common.ObjectiveTo assess the safety and efficacy of thrombectomy for AIS using Solitaire for patients treated in the roll-in period of the Solitaire With the Intention For Thrombectomy (SWIFT) trial, which represented the first clinical use of the device for these interventionalists.MethodsProspectively collected demographic, clinical, and angiographic data on patients treated in the initial roll-in and subsequent randomized phases of the SWIFT study were collected and analyzed. Key statistical analyses were validated by an independent external statistician.ResultsPatients in the roll-in period achieved equivalently high rates of reperfusion (55%) compared with those treated with the device in the randomized phase (61%). Rates of adverse events were comparable (13% vs. 9%). Rates of good neurological outcome were equivalent between the roll-in and randomized patients treated with Solitaire (63% vs. 58%). Including the roll-in patients strengthened the conclusions of the study, that reperfusion rates without symptomatic hemorrhage with Solitaire were greater than with Merci (59% vs. 24%, p

Published
2016

22. Characterization of Antibody Bipolar Bridging Mediated by the Human Cytomegalovirus Fc Receptor gp68

Author

Ndjamen, Blaise, Joshi, Devashish S, Fraser, Scott E, and Bjorkman, Pamela J

Subjects
Immunization, Infectious Diseases, Cytomegalovirus, Endocytosis, Endosomes, Humans, Immunoglobulin G, Membrane Glycoproteins, Receptors, IgG, Viral Proteins, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology
Abstract

The human cytomegalovirus glycoprotein gp68 functions as an Fc receptor for host IgGs and can form antibody bipolar bridging (ABB) complexes in which gp68 binds the Fc region of an antigen-bound IgG. Here we show that gp68-mediated endocytosis transports ABB complexes into endosomes, after which the complex is routed to lysosomes, presumably for degradation. These results suggest gp68 contributes to evasion of IgG-mediated immune responses by mediating destruction of host IgG and viral antigens.

Published
2016

23. Adopting a Patient-Centered Approach to Primary Outcome Analysis of Acute Stroke Trials Using a Utility-Weighted Modified Rankin Scale

Author

Chaisinanunkul, Napasri, Adeoye, Opeolu, Lewis, Roger J, Grotta, James C, Broderick, Joseph, Jovin, Tudor G, Nogueira, Raul G, Elm, Jordan J, Graves, Todd, Berry, Scott, Lees, Kennedy R, Barreto, Andrew D, Saver, Jeffrey L, Furlan, Anthony, Baxter, Blaise, Lutsep, Helmi L, Ribo, Marc, Jansen, Olav, Gupta, Rishi, and Pereira, Vitor Mendes

Subjects
Epidemiology, Health Sciences, Stroke, Clinical Trials and Supportive Activities, Clinical Research, Neurosciences, Cerebrovascular, Brain Disorders, Good Health and Well Being, Clinical Trials as Topic, Humans, Patient-Centered Care, Severity of Illness Index, Treatment Outcome, blood pressure, stroke, stroke management, thrombolysis, DAWN Trial and MOST Trial Steering Committees, Additional contributors from DAWN Trial Steering Committee, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Neurology & Neurosurgery, Clinical sciences, Allied health and rehabilitation science
Abstract

Background and purposeAlthough the modified Rankin Scale (mRS) is the most commonly used primary end point in acute stroke trials, its power is limited when analyzed in dichotomized fashion and its indication of effect size challenging to interpret when analyzed ordinally. Weighting the 7 Rankin levels by utilities may improve scale interpretability while preserving statistical power.MethodsA utility-weighted mRS (UW-mRS) was derived by averaging values from time-tradeoff (patient centered) and person-tradeoff (clinician centered) studies. The UW-mRS, standard ordinal mRS, and dichotomized mRS were applied to 11 trials or meta-analyses of acute stroke treatments, including lytic, endovascular reperfusion, blood pressure moderation, and hemicraniectomy interventions.ResultsUtility values were 1.0 for mRS level 0; 0.91 for mRS level 1; 0.76 for mRS level 2; 0.65 for mRS level 3; 0.33 for mRS level 4; 0 for mRS level 5; and 0 for mRS level 6. For trials with unidirectional treatment effects, the UW-mRS paralleled the ordinal mRS and outperformed dichotomous mRS analyses. Both the UW-mRS and the ordinal mRS were statistically significant in 6 of 8 unidirectional effect trials, whereas dichotomous analyses were statistically significant in 2 to 4 of 8. In bidirectional effect trials, both the UW-mRS and ordinal tests captured the divergent treatment effects by showing neutral results, whereas some dichotomized analyses showed positive results. Mean utility differences in trials with statistically significant positive results ranged from 0.026 to 0.249.ConclusionsA UW-mRS performs similar to the standard ordinal mRS in detecting treatment effects in actual stroke trials and ensures the quantitative outcome is a valid reflection of patient-centered benefits.

Published
2015

24. Developing a prognostic micro-RNA signature for human cervical carcinoma.

Author

How, Christine, Pintilie, Melania, Bruce, Jeff P, Hui, Angela BY, Clarke, Blaise A, Wong, Philip, Yin, Shaoming, Yan, Rui, Waggott, Daryl, Boutros, Paul C, Fyles, Anthony, Hedley, David W, Hill, Richard P, Milosevic, Michael, and Liu, Fei-Fei

Subjects
Humans, MicroRNAs, Prognosis, Disease-Free Survival, Paraffin Embedding, Reproducibility of Results, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Adult, Aged, Aged, 80 and over, Middle Aged, Uterine Cervical Neoplasms, Female, Young Adult, and over, Gene Expression Regulation, Neoplastic, General Science & Technology
Abstract

Cervical cancer remains the third most frequently diagnosed and fourth leading cause of cancer death in women worldwide. We sought to develop a micro-RNA signature that was prognostic for disease-free survival, which could potentially allow tailoring of treatment for cervical cancer patients. A candidate prognostic 9-micro-RNA signature set was identified in the training set of 79 frozen specimens. However, three different approaches to validate this signature in an independent cohort of 87 patients with formalin-fixed paraffin-embedded (FFPE) specimens, were unsuccessful. There are several challenges and considerations associated with developing a prognostic micro-RNA signature for cervical cancer, namely: tumour heterogeneity, lack of concordance between frozen and FFPE specimens, and platform selection for global micro-RNA expression profiling in this disease. Our observations provide an important cautionary tale for future miRNA signature studies for cervical cancer, which can also be potentially applicable to miRNA profiling studies involving other types of human malignancies.

Published
2015

25. Hotspot activating PRKD1 somatic mutations in polymorphous low-grade adenocarcinomas of the salivary glands

Author

Weinreb, Ilan, Piscuoglio, Salvatore, Martelotto, Luciano G, Waggott, Daryl, Ng, Charlotte KY, Perez-Ordonez, Bayardo, Harding, Nicholas J, Alfaro, Javier, Chu, Kenneth C, Viale, Agnes, Fusco, Nicola, da Cruz Paula, Arnaud, Marchio, Caterina, Sakr, Rita A, Lim, Raymond, Thompson, Lester DR, Chiosea, Simion I, Seethala, Raja R, Skalova, Alena, Stelow, Edward B, Fonseca, Isabel, Assaad, Adel, How, Christine, Wang, Jianxin, de Borja, Richard, Chan-Seng-Yue, Michelle, Howlett, Christopher J, Nichols, Anthony C, Wen, Y Hannah, Katabi, Nora, Buchner, Nicholas, Mullen, Laura, Kislinger, Thomas, Wouters, Bradly G, Liu, Fei-Fei, Norton, Larry, McPherson, John D, Rubin, Brian P, Clarke, Blaise A, Weigelt, Britta, Boutros, Paul C, and Reis-Filho, Jorge S

Subjects
Agricultural, Veterinary and Food Sciences, Biological Sciences, Bioinformatics and Computational Biology, Genetics, Agricultural Biotechnology, Cancer, Digestive Diseases, Adenocarcinoma, Amino Acid Sequence, Animals, Humans, Immunohistochemistry, Immunoprecipitation, Mice, Microscopy, Confocal, Models, Molecular, Molecular Sequence Data, Mutagenesis, Mutation, Missense, NIH 3T3 Cells, Protein Kinase C, Salivary Gland Neoplasms, Sequence Alignment, Sequence Analysis, DNA, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Polymorphous low-grade adenocarcinoma (PLGA) is the second most frequent type of malignant tumor of the minor salivary glands. We identified PRKD1 hotspot mutations encoding p.Glu710Asp in 72.9% of PLGAs but not in other salivary gland tumors. Functional studies demonstrated that this kinase-activating alteration likely constitutes a driver of PLGA.

Published
2014

26. Lennox-Gastaut syndrome: a consensus approach to differential diagnosis.

Author

Bourgeois, Blaise FD, Douglass, Laurie M, and Sankar, Raman

Subjects
Humans, Diagnosis, Differential, Electroencephalography, Consensus, Cognition Disorders, Algorithms, Lennox Gastaut Syndrome, Encephalopathy, Epilepsy, Infantile spasms, Seizure, West syndrome, Neurodegenerative, Pediatric, Clinical Research, 4.2 Evaluation of markers and technologies, 4.1 Discovery and preclinical testing of markers and technologies, 7.3 Management and decision making, Diagnosis, Differential, Neurology & Neurosurgery, Clinical Sciences, Neurosciences
Abstract

Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy that shares many features and characteristics of other treatment-resistant childhood epilepsies. Accurate and early diagnosis is essential to both prognosis and overall patient management. However, accurate diagnosis of LGS can be clinically challenging. This article summarizes key characteristics of LGS and areas of overlap with other childhood epilepsies. Drawing upon input from a committee of established LGS experts convened in June 2012 in Chicago, Illinois, the authors highlight key diagnostic tests for making the differential diagnosis and propose a diagnostic scheme for people with suspected LGS.

Published
2014

27. Small cell carcinoma of the ovary, hypercalcemic type, displays frequent inactivating germline and somatic mutations in SMARCA4

Author

Ramos, Pilar, Karnezis, Anthony N, Craig, David W, Sekulic, Aleksandar, Russell, Megan L, Hendricks, William PD, Corneveaux, Jason J, Barrett, Michael T, Shumansky, Karey, Yang, Yidong, Shah, Sohrab P, Prentice, Leah M, Marra, Marco A, Kiefer, Jeffrey, Zismann, Victoria L, McEachron, Troy A, Salhia, Bodour, Prat, Jaime, D'Angelo, Emanuela, Clarke, Blaise A, Pressey, Joseph G, Farley, John H, Anthony, Stephen P, Roden, Richard BS, Cunliffe, Heather E, Huntsman, David G, and Trent, Jeffrey M

Subjects
Cancer, Rare Diseases, Ovarian Cancer, Genetics, Base Sequence, Carcinoma, Small Cell, Chromatin Assembly and Disassembly, Chromosome Mapping, Computational Biology, DNA Helicases, DNA, Complementary, Electrophoresis, Polyacrylamide Gel, Exome, Female, Gene Library, Humans, Immunohistochemistry, Molecular Sequence Data, Mutation, Nuclear Proteins, Ovarian Neoplasms, Sequence Analysis, DNA, Transcription Factors, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Small cell carcinoma of the ovary of hypercalcemic type (SCCOHT) is an extremely rare, aggressive cancer affecting children and young women. We identified germline and somatic inactivating mutations in the SWI/SNF chromatin-remodeling gene SMARCA4 in 75% (9/12) of SCCOHT cases in addition to SMARCA4 protein loss in 82% (14/17) of SCCOHT tumors but in only 0.4% (2/485) of other primary ovarian tumors. These data implicate SMARCA4 in SCCOHT oncogenesis.

Published
2014

28. Nedd4 is a specific E3 ubiquitin ligase for the NMDA receptor subunit GluN2D

Author

Gautam, Vivek, Trinidad, Jonathan C, Rimerman, Ronald A, Costa, Blaise M, Burlingame, Alma L, and Monaghan, Daniel T

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Neurosciences, Brain Disorders, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Neurological, Animals, Down-Regulation, Endosomal Sorting Complexes Required for Transport, HEK293 Cells, Humans, Membrane Potentials, Mice, Nedd4 Ubiquitin Protein Ligases, Oocytes, Protein Interaction Domains and Motifs, Protein Subunits, Rats, Receptors, N-Methyl-D-Aspartate, Ubiquitin-Protein Ligases, Ubiquitination, Xenopus Proteins, Xenopus laevis, NMDA receptors, G1uN2D subunit, Glutamate, Nedd4, Ubiquitin ligase, Excitotoxicity, Proteomics, Mass spectrometry, GluN2D subunit, Psychology, Neurology & Neurosurgery, Pharmacology and pharmaceutical sciences, Biological psychology
Abstract

NMDA receptors are a family of glutamate-gated ion channels that regulate various CNS functions such as synaptic plasticity and learning. However hypo- or hyper-activation of NMDA receptors is critically involved in many neurological and psychiatric conditions such as pain, stroke, epilepsy, neurodegeneration, schizophrenia, and depression. Thus, it is important to identify mechanisms (such as by targeted ubiquitination) that regulate the levels of individual subtypes of NMDA receptors. In this study, we used a series of tagged, carboxy terminal constructs of GluN2D to identify associating proteins from rat brain. Of seven different GluN2D C-terminal fragments used as bait, only the construct containing amino acids 983-1097 associated with an E3 ubiquitin ligase, Nedd4. A direct interaction between GluN2D and Nedd4 was confirmed both in vivo and in vitro. This association is mediated by an interaction between GluN2D's C-terminal PPXY motif and the 2nd and 3rd WW domains of Nedd4. Of the four GluN2 subunits, Nedd4 directly interacted with GluN2D and also weakly with GluN2A. Nedd4 coexpression with GluN2D enhances GluN2D ubiquitination and reduces GluN1/GluN2D NMDA receptor responses. These results identify Nedd4 as a novel binding partner for GluN2D and suggest a mechanism for the regulation of NMDA receptors that contain GluN2D subunits through ubiquitination-dependent downregulation. This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'.

Published
2013

29. MicroRNA-196b regulates the homeobox B7-vascular endothelial growth factor axis in cervical cancer.

Author

How, Christine, Hui, Angela BY, Alajez, Nehad M, Shi, Wei, Boutros, Paul C, Clarke, Blaise A, Yan, Rui, Pintilie, Melania, Fyles, Anthony, Hedley, David W, Hill, Richard P, Milosevic, Michael, and Liu, Fei-Fei

Subjects
Cell Line, Tumor, Humans, Carcinoma, Squamous Cell, Vascular Endothelial Growth Factor A, Homeodomain Proteins, MicroRNAs, RNA, Small Interfering, RNA, Messenger, Antineoplastic Agents, Survival Analysis, Signal Transduction, Cell Proliferation, Transcription, Genetic, Gene Expression Regulation, Neoplastic, Gamma Rays, Adult, Aged, Aged, 80 and over, Middle Aged, Uterine Cervical Neoplasms, Female, and over, Carcinoma, Squamous Cell, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, RNA, Messenger, Small Interfering, Transcription, Genetic, General Science & Technology
Abstract

The down-regulation of microRNA-196b (miR-196b) has been reported, but its contribution to cervical cancer progression remains to be investigated. In this study, we first demonstrated that miR-196b down-regulation was significantly associated with worse disease-free survival (DFS) for cervical cancer patients treated with combined chemo-radiation. Secondly, using a tri-modal approach for target identification, we determined that homeobox-B7 (HOXB7) was a bona fide target for miR-196b, and in turn, vascular endothelial growth factor (VEGF) was a downstream transcript regulated by HOXB7. Reconstitution of miR-196b expression by transient transfection resulted in reduced cell growth, clonogenicity, migration and invasion in vitro, as well as reduced tumor angiogenesis and tumor cell proliferation in vivo. Concordantly, siRNA knockdown of HOXB7 or VEGF phenocopied the biological effects of miR-196b over-expression. Our findings have demonstrated that the miR-196b/HOXB7/VEGF pathway plays an important role in cervical cancer progression; hence targeting this pathway could be a promising therapeutic strategy for the future management of this disease.

Published
2013

30. 25 mm Hg versus 35 mm Hg elastic compression stockings to prevent post-thrombotic syndrome after deep vein thrombosis (CELEST): a randomised, double-blind, non-inferiority trial

Author

Jean-Philippe Galanaud, Céline Genty-Vermorel, Marie-Thérèse Barrellier, François Becker, Violaine Jabbour, Sophie Blaise, Alessandra Bura-Rivière, Alexa Comte, Claire Grange, Herve Guenneguez, Mario Maufus, Pierre Ouvry, Cécile Richaud, Carole Rolland, Jeannot Schmidt, Marie-Antoinette Sevestre, François Verrière, Jean-Luc Bosson, Olivier Pichot, Hervé Guenneguez, Anna Di Maio, Francis Couturaud, Marc Danguy Des Déserts, Patrick Mismetti, Damien Laneelle, Béatrice Terriat, Audrey Stansal, Myriam Martin, Constant Quashie, Mickaël Bonaldi, Patrick Lanoye, Francine Ponchaux-Crépin, Toufek Berremili, Marie-Antoinette Sevestre-Pietri, Santhi Samy-Modeliar, Azeddine Addala, Luc Toffin, Bruno Rouquet, Maïlys Michot-Casbas, Guillaume Lacaze, Pierre-Marie Roy, Cécile Durant, Anne-Laure Baldassini-Esquis, Alain Cazanave, Damien Rouvière, Hélène Skolka, Tewfik Salem, Jean-Michel Monsallier, Benoit Roger, Thien-Quang Tra, Mutendi Kalolwa, Antoine Diard, Marc Lambert, Mebarka Taiar, Céline Gaudout, Sylvain Ancey, and Christine Jurus

Subjects
Adult, Male, Double-Blind Method, Leg Ulcer, Humans, Female, Hematology, Middle Aged, Stockings, Compression, Postthrombotic Syndrome, Veins
Abstract

The optimal strength of compression needed to prevent post-thrombotic syndrome (PTS) after a proximal deep vein thrombosis (DVT) is debated. We aimed to assess whether 25 mm Hg elastic compression stockings (ECS) are non-inferior to 35 mm Hg ECS in preventing PTS after a DVT.In this multicentre, double-blind, non-inferiority, randomised controlled trial, we enrolled adults (≥18 years) with a first ipsilateral proximal DVT attending 46 French vascular medicine hospital departments or private practices. Participants were randomly allocated (1:1, stratified by centre, age, and sex; with varying block sizes of two and four) to wear 25 mm Hg or 35 mm Hg ECS for 2 years. The primary outcome was the cumulative rate of PTS 2 years after inclusion, defined by a Villalta scale (≥5). Efficacy was assessed by intention-to-treat and in eligible participants who had complete primary outcome data. A per-protocol analysis was also conducted among compliant patients as a secondary outcome measure. Safety was assessed in all participants who used ECS at least once, and for which we have at least some tolerance information during follow-up. The margin for non-inferiority was 12·5%. This study is registered with ClinicalTrials.gov, NCT01578122, and has been completed.Between June 28, 2012, and July 21, 2017, we enrolled 341 eligible participants who consented to randomisation. 233 (68%) were men and median age was 59 years (IQR 45-70). Collection of ethnicity and race as a routine research variable is not authorised in France. Median follow-up was 735 days (IQR 721-760). 249 (73%) had complete data at 2 years. For the primary analysis, 40 (31%) of 129 participants with complete data in the 25 mm Hg ECS group and 40 (33%) of 120 in the 35 mm Hg group had PTS (absolute difference -2·3% [90% CI -12·1 to 7·4], pAlthough we did not reach the prespecified sample size, our results suggest that 25 mm Hg ECS are non-inferior to 35 mm Hg ECS in preventing PTS. Larger more powerful studies are needed.Laboratoires Innothera, France.

Published
2022
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31. Cardiac Effort to Compare Clinic and Remote 6-Minute Walk Testing in Pulmonary Arterial Hypertension

Author

Daniel Lachant, Ethan Kennedy, Blaise Derenze, Allison Light, Michael Lachant, and R. James White

Subjects
Pulmonary and Respiratory Medicine, Pulmonary Arterial Hypertension, Exercise Tolerance, SARS-CoV-2, Exercise Test, Humans, Reproducibility of Results, COVID-19, Walk Test, Familial Primary Pulmonary Hypertension, Walking, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine
Abstract

The SARS-CoV-2 pandemic has limited objective physiologic assessments. A standardized remote alternative is not currently available. "Cardiac effort" (CE), that is, the total number of heart beats divided by the 6-min walk test (6MWT) distance (beats/m), has improved reproducibility in the 6MWT and correlated with right ventricular function in pulmonary arterial hypertension.Can a chest-based accelerometer estimate 6MWT distance remotely? Is remote cardiac effort more reproducible than 6MWT distance when compared with clinic assessment?This was a single-center, prospective observational study, with institutional review board approval, completed between October 2020 and April 2021. Group 1 subjects with pulmonary arterial hypertension, receiving stable therapy for90 days, completed four to six total 6MWTs during a 2-week period to assess reproducibility. The first and last 6MWTs were performed in the clinic; two to four remote 6MWTs were completed at each participant's discretion. Masks were not worn. BioStamp nPoint sensors (MC10) were worn on the chest to measure heart rate and accelerometry. Two blinded readers counted laps, using accelerometry data obtained on the clinic or user-defined course. Averages of clinic variables and remote variables were used for Wilcoxon matched-pairs signed rank tests, Bland-Altman plots, or Spearman correlation coefficients.Estimated 6MWT distance, using the MC10, correlated strongly with directly measured 6MWT distance (r = 0.99; P .0001; in 20 subjects). Remote 6MWT distances were shorter than clinic 6MWT distances: 405 m (330-464 m) vs 389 m (312-430 m) (P = .002). There was no difference between in-clinic and remote CE: 1.75 beats/m (1.48-2.20 beats/m) vs 1.86 beats/m (1.57-2.14 beats/m) (P = .14).Remote 6MWT was feasible on a user-defined course; 6MWT distance was shorter than clinic distance. CE calculated by chest heart rate and accelerometer-estimated distance provides a reproducible remote assessment of exercise tolerance, comparable to the clinic-measured value.

Published
2022
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32. Comparative evaluation of socioeconomic insecurity in peripheral and coronary artery disease patients

Author

Marion, Joly, Pierre, Gillois, Bernadette, Satger, Sophie, Blaise, and Gilles, Pernod

Subjects
Male, Peripheral Arterial Disease, Risk Factors, Humans, Educational Status, Female, Coronary Artery Disease, Prospective Studies, Cardiology and Cardiovascular Medicine
Abstract

Cardiovascular disease represents the leading cause of death worldwide. Socioeconomic deprivation is a risk factor for cardiovascular disease. We have previously shown that precariousness was more frequent in symptomatic peripheral artery disease (PAD) patients than in the general population. According to a previous study, coronary artery disease (CAD) patients have a higher level of education than CAD with PAD, but no study directly compared the level of precariousness in PAD and CAD patients.To measure and compare the level of socioeconomic insecurity in patients suffering from symptomatic PAD with those suffering from isolated CAD, i.e without symptomatic PAD.We conducted an observational, cohort, prospective, multicenter study. Patients suffering from symptomatic PAD or CAD were recruited through the medical or surgical vascular or cardiology departments, or the vascular rehabilitation center. The EPICES score and the INSEE parameters were used for analysis. The individual is considered precarious when his or her score is greater than or equal to 30. Cardiovascular risk factors and peripheral arterial disease stages were also collected.In total, 230 patients were included. According to the EPICES score, 47.8% [95%CI, 38.7-56.7] of patients with symptomatic PAD were in a precarious situation compared to 17.4% [95%CI, 10.5-24.3] of patients suffering from isolated CAD (P0.001). The mean EPICES score was 33.3 (SD 22.5) in the PAD and 16.9 (SD 17.02) in the CAD population, respectively (P0.001). In the PAD population, the level of education was low, with an under-representation of patients with a baccalaureate or higher education degree: 21.7% [95%CI, 14.2-29.3] vs. 41.7% [95%CI, 32.7-50.7] in the PAD and CAD populations, respectively. There was also an under-representation of executives and intellectual and intermediate professions in the PAD population, 18.3% [95%CI, 11.2-25.3], compared to the CAD population, 31.3% [95%CI, 22.8-39.8].PAD patients are more precarious than patients suffering from CAD. A better detection of socioeconomic deprivation in patients suffering from peripheral arterial disease could allow comprehensive care and thus hope for an improvement in terms of morbidity and mortality.

Published
2022
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33. Recurrent KAT6B/A::KANSL1 Fusions Characterize a Potentially Aggressive Uterine Sarcoma Morphologically Overlapping With Low-grade Endometrial Stromal Sarcoma

Author

Abbas Agaimy, Blaise A. Clarke, David L. Kolin, Cheng-Han Lee, Jen-Chieh Lee, W. Glenn McCluggage, Patrik Pöschke, Robert Stoehr, David Swanson, Gulisa Turashvili, Matthias W. Beckmann, Arndt Hartmann, Cristina R. Antonescu, and Brendan C. Dickson

Subjects
Adult, Aged, 80 and over, Leiomyoma, Sarcoma, Endometrial Stromal, Nuclear Proteins, Soft Tissue Neoplasms, Middle Aged, Pathology and Forensic Medicine, Endometrial Neoplasms, Endometrial Stromal Tumors, Uterine Neoplasms, Biomarkers, Tumor, Humans, Surgery, Female, Neprilysin, Anatomy, Aged, Histone Acetyltransferases
Abstract

With the widespread application of next-generation sequencing, the genetic landscape of uterine mesenchymal neoplasms has been evolving rapidly to include several recently identified fusion genes. Although chromosomal rearrangements involving the 10q22 and 17q21.31 loci have been reported in occasional uterine leiomyomas decades ago, the corresponding KAT6B::KANSL1 fusion has been only recently identified in 2 uterine tumors diagnosed as leiomyoma and leiomyosarcoma. We herein describe 13 uterine stromal neoplasms carrying a KAT6B::KANSL1 (n=11) and KAT6A::KANSL1 (n=2) fusion. Patient ages ranged from 33 to 81 years (median, 49 y). Tumor size was 2.6 to 23.5 cm (median, 8.2 cm). Nine tumors were myometrium-centered, and 3 had an intracavitary component. Original diagnoses were mostly low-grade endometrial stromal sarcoma (LG-ESS; 10 cases) with atypical features (limited CD10 expression, sex cord-like features, pericytic vasculature, and frequent myxoid changes). Treatment was hysterectomy±bilateral salpingo-oophorectomy (10), myomectomy (1), and curettage (2). Five patients were disease-free at 6 to 34 months, 3 (27%) died of disease at 2 to 47 months, and 3 were alive with disease at 2, 17, and 17 years. Histologically, most tumors showed variable overlap with LG-ESS, but they were generally well-circumscribed lacking the extensive permeative and angioinvasive growth typical of LG-ESS. They were composed of monotonous medium-sized oval and spindle cells arranged into diffuse sheets with prominent spiral-type arterioles and frequent pericytoma-like vascular pattern. Variable myxoid stromal changes were frequent. Mitotic activity ranged from 1 to20 in 10 HPFs. Immunohistochemistry showed variable expression of CD10 (12/13), estrogen receptor (8/11), progesterone receptor (8/11), smooth muscle actin (9/11), desmin (4/12), h-caldesmon (2/10), calretinin (3/8), inhibin (1/7), WT1 (4/7), cyclin D1 (5/11; diffuse in only 1 case), and pankeratin (5/10). This series characterizes a KAT6B/A::KANSL1 fusion-positive uterine stromal neoplasm within the morphologic spectrum of LG-ESS but with atypical features. The relationship of these neoplasms to genuine LG-ESS remains unclear. This molecular subtype of uterine endometrial stromal sarcoma has the potential for an unfavorable clinical course despite the absence of widely invasive growth; nevertheless, analysis of more cases is necessary to delineate the phenotypic spectrum and biological potential of this tumor.

Published
2023

34. A history of variceal bleeding is associated with further bleeding under atezolizumab–bevacizumab in patients with <scp>HCC</scp>

Author

Edouard Larrey, Bertille Campion, Manon Evain, Philippe Sultanik, Lorraine Blaise, Héloïse Giudicelli, Mathilde Wagner, Philippe Cluzel, Marika Rudler, Nathalie Ganne‐Carrié, Dominique Thabut, and Manon Allaire

Subjects
Male, Bevacizumab, Liver Cirrhosis, Carcinoma, Hepatocellular, Hepatology, Liver Neoplasms, Humans, Prospective Studies, Sorafenib, Esophageal and Gastric Varices, Gastrointestinal Hemorrhage, Retrospective Studies
Abstract

Atezolizumab-bevacizumab is the new standard for advanced hepatocellular carcinoma (HCC) but its impact on portal hypertension (PHT) is unknown. We aimed to identify predictive factors of acute variceal bleeding (AVB) and to monitor PHT parameters under treatment.We conducted a prospective study including all cirrhotic patients treated with atezolizumab-bevacizumab since 2020. We performed monitoring of PHT using upper endoscopy at inclusion and at 6 months and hepatic venous pressure gradient (HVPG) at inclusion, 3 and 6 months after the beginning of treatment. We also included a retrospective series of patients treated with sorafenib. Time-to-events data were estimated by Kaplan-Meier with the log-rank test, along with Cox models.Forty-three patients treated with atezolizumab-bevacizumab were included (male 79.1%, Child-Pugh A 86%). At baseline, 48.8% were treated with curative anticoagulation, 16.3% already experienced AVB and 25.6% had large oesophageal varices (EV). Sorafenib group characteristics were similar. Vascular invasion was present in 60.5% and median was HVPG 8.5 mm Hg. No significant modification in HVPG and EV size was observed at 6 months in the whole cohort but also when considering vascular invasion and radiological response. 14% presented AVB within a median time of occurrence of 3 months, without bleeding-related death. In multivariate analysis, history of AVB (HR = 10.58, p = .03) was associated with AVB. AVB incidence was higher in atezolizumab-bevacizumab compared to sorafenib group (21% vs. 5% at 1 year, p = .02).Atezolizumab-bevacizumab treatment was associated with a higher risk of AVB compared to sorafenib. A history of AVB was associated with AVB during follow-up, which questions the use of bevacizumab in this setting.

Published
2022
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35. Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion

Author

Chunrong, Tao, Raul G, Nogueira, Yuyou, Zhu, Jun, Sun, Hongxing, Han, Guangxiong, Yuan, Changming, Wen, Peiyang, Zhou, Wenhuo, Chen, Guoyong, Zeng, Yuwen, Li, Zhengfei, Ma, Chuanqing, Yu, Junfeng, Su, Zhiming, Zhou, Zhongjun, Chen, Geng, Liao, Yaxuan, Sun, Youquan, Ren, Hui, Zhang, Jie, Chen, Xincan, Yue, Guodong, Xiao, Li, Wang, Rui, Liu, Wenhua, Liu, Yong, Liu, Chao, Zhang, Tianlong, Liu, Jianlong, Song, Rui, Li, Pengfei, Xu, Yamei, Yin, Guoping, Wang, Blaise, Baxter, Adnan I, Qureshi, Xinfeng, Liu, Wei, Hu, and Yali, Zhang

Subjects
Endovascular Procedures, Arterial Occlusive Diseases, Recovery of Function, General Medicine, Brain Ischemia, Stroke, Treatment Outcome, Fibrinolytic Agents, Basilar Artery, Quality of Life, Humans, Administration, Intravenous, Thrombolytic Therapy, Prospective Studies, Intracranial Hemorrhages, Thrombectomy
Abstract

Data from trials investigating the effects and risks of endovascular thrombectomy for the treatment of stroke due to basilar-artery occlusion are limited.We conducted a multicenter, prospective, randomized, controlled trial of endovascular thrombectomy for basilar-artery occlusion at 36 centers in China. Patients were assigned, in a 2:1 ratio, within 12 hours after the estimated time of basilar-artery occlusion to receive endovascular thrombectomy or best medical care (control). The primary outcome was good functional status, defined as a score of 0 to 3 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]), at 90 days. Secondary outcomes included a modified Rankin scale score of 0 to 2, distribution across the modified Rankin scale score categories, and quality of life. Safety outcomes included symptomatic intracranial hemorrhage at 24 to 72 hours, 90-day mortality, and procedural complications.Of the 507 patients who underwent screening, 340 were in the intention-to-treat population, with 226 assigned to the thrombectomy group and 114 to the control group. Intravenous thrombolysis was used in 31% of the patients in the thrombectomy group and in 34% of those in the control group. Good functional status at 90 days occurred in 104 patients (46%) in the thrombectomy group and in 26 (23%) in the control group (adjusted rate ratio, 2.06; 95% confidence interval [CI], 1.46 to 2.91, P0.001). Symptomatic intracranial hemorrhage occurred in 12 patients (5%) in the thrombectomy group and in none in the control group. Results for the secondary clinical and imaging outcomes were generally in the same direction as those for the primary outcome. Mortality at 90 days was 37% in the thrombectomy group and 55% in the control group (adjusted risk ratio, 0.66; 95% CI, 0.52 to 0.82). Procedural complications occurred in 14% of the patients in the thrombectomy group, including one death due to arterial perforation.In a trial involving Chinese patients with basilar-artery occlusion, approximately one third of whom received intravenous thrombolysis, endovascular thrombectomy within 12 hours after stroke onset led to better functional outcomes at 90 days than best medical care but was associated with procedural complications and intracerebral hemorrhage. (Funded by the Program for Innovative Research Team of the First Affiliated Hospital of USTC and others; ATTENTION ClinicalTrials.gov number, NCT04751708.).

Published
2022
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36. Impact of sarcopenia on tumor response and survival outcomes in patients with hepatocellular carcinoma treated by trans-arterial (chemo)-embolization

Author

Gael, Roth, Yann, Teyssier, Maxime, Benhamou, Mélodie, Abousalihac, Stefano, Caruso, Christian, Sengel, Olivier, Seror, Julien, Ghelfi, Arnaud, Seigneurin, Nathalie, Ganne-Carrie, Elia, Gigante, Lorraine, Blaise, Olivier, Sutter, Thomas, Decaens, and Jean-Charles, Nault

Subjects
Sarcopenia, Carcinoma, Hepatocellular, Liver Neoplasms, Malnutrition, Gastroenterology, Humans, General Medicine, Chemoembolization, Therapeutic, Retrospective Studies
Abstract

At the diagnosis of hepatocellular carcinoma (HCC), more than 90% of HCC patients present cirrhosis, a clinical condition often associated to malnutrition. Sarcopenia is an indirect marker of malnutrition assessable on computed tomography (CT).To evaluate the prognostic value of sarcopenia in patients with HCC treated by trans-arterial (chemo)-embolization.Patients with HCC treated by a first session of trans-arterial (chemo)embolization and an available CT scan before treatment were included. Sarcopenia was assessed using skeletal muscle index at baseline and at the first radiological assessment. Radiological response was recorded after the first session of treatment using mRECIST.Of 225 patients treated by trans-arterial bland embolization (Sarcopenia is associated with tumor progression and poor survival outcomes after trans-arterial (chemo)-embolization for HCC.

Published
2022
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37. Impact of second-degree related donor on the outcomes of T cell-replete haploidentical transplantation with post-transplant cyclophosphamide

Author

Jacopo Mariotti, Anna Maria Raiola, Andrea Evangelista, Samia Harbi, Francesca Patriarca, Michele Angelo Carella, Massimo Martino, Antonio Risitano, Alessandro Busca, Luisa Giaccone, Lucia Brunello, Emanuela Merla, Lucia Savino, Barbara Loteta, Giuseppe Console, Renato Fanin, Alessandra Sperotto, Luana Marano, Serena Marotta, Camilla Frieri, Simona Sica, Patrizia Chiusolo, Christian Chabannon, Sabine Furst, Armando Santoro, Andrea Bacigalupo, Benedetto Bruno, Didier Blaise, Domenico Mavilio, Stefania Bramanti, Raynier Devillier, Emanuele Angelucci, and Luca Castagna

Subjects
Transplantation, Transplantation Conditioning, T-Lymphocytes, Transplantation, Haploidentical, Hematopoietic Stem Cell Transplantation, Humans, Graft vs Host Disease, Hematology, Cyclophosphamide, Retrospective Studies
Abstract

Donor selection may contribute to improve clinical outcomes of T cell-replete haploidentical stem cell transplantation (Haplo-SCT) with post-transplant cyclophosphamide (PT-Cy). Impact of second-degree related donor (SRD) was not fully elucidated in this platform. We retrospectively compared the outcome of patients receiving Haplo-SCT either from a SRD (n = 31) or a first-degree related donor (FRD, n = 957). Median time to neutrophil and platelet recovery did not differ between a SRD and a FRD transplant (p = 0.599 and 0.587). Cumulative incidence of grade II-IV acute graft-versus host disease (GVHD) and moderate-severe chronic GVHD was 13% and 19% after SRD vs 24% (p = 0.126) and 13% (p = 0.395) after FRD transplant. One-year cumulative incidence of non-relapse mortality (NRM) was 19% for SRD and 20% for FRD (p = 0.435) cohort. The 3-year probability of overall survival (OS) and progression-free survival (PFS) was 42% vs 55% (p = 0.273) and 49% vs 35% (p = 0.280) after SRD and FRD transplant, respectively. After propensity score adjustment or matched pair analysis, the outcome of patients receiving Haplo-SCT from a SRD or a FRD did not differ in terms of NRM, OS, PFS, acute and chronic GVHD. Our results suggest that a SRD is a viable option for Haplo-SCT with PT-Cy when a FRD is not available.

Published
2022
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38. A randomised, open‐label, parallel‐group, multicentre, comparative study to compare the efficacy and safety of Exufiber® with Aquacel® Extra™ dressings in exuding venous and mixed aetiology leg ulcers

Author

Bo Joergensen, Sophie Blaise, and Ann‐Sofie Svensson

Subjects
Adult, Wound Healing, Treatment Outcome, Carboxymethylcellulose Sodium, Leg Ulcer, Humans, Surgery, Prospective Studies, Dermatology, Bandages
Abstract

The performance and safety of Exufiber® gelling fibre and Aquacel® Extra™ Hydrofiber® wound dressings were compared for the management of chronic, exuding leg ulcers. The 6-week study (≤ 24 weeks in a subgroup of subjects) was a randomised, open-label, parallel-group, multicentre, non-inferiority design. Adults (n = 248, 30-97 years of age) were randomised to either Exufiber® or Aquacel® Extra™ dressing. The dressings were applied at baseline and evaluations of wound condition and performance of the dressing were recorded at 1, 2, 3, 4, and 6 weeks. The primary efficacy endpoint was the percentage reduction in wound area at 6 weeks relative to baseline, in the per protocol (PP) population. A median relative reduction of 50% for Exufiber® (n = 100) vs 42% for Aquacel® Extra™ (n = 107) was demonstrated in the PP population (P = 0.093) and confirmed in the intention-to-treat population. As the mean and 95% confidence interval for the difference in relative wound area reduction between groups at 6 weeks was -29.4% (-63.5; 3.2), and the lower limit did not exceed 12%, non-inferiority of Exufiber® was concluded. Both dressings were well tolerated and no safety concerns were identified in both groups. Clinicians' satisfaction with the dressings was higher for Exufiber® than for Aquacel® Extra™ in terms of ease of use and management of exudate, slough, and blood.

Published
2022
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39. Understanding the performance of a pan-African intervention to reduce postoperative mortality: a mixed-methods process evaluation of the ASOS-2 trial

Author

Nicola Vickery, Timothy Stephens, Leon du Toit, Dawid van Straaten, Rupert Pearse, Alexandra Torborg, Lucy Rolt, Mariechen Puchert, Graham Martin, Bruce Biccard, Bruce M. Biccard, Maia Lesosky, Tim Stephens, Landon Myer, Agya BA. Prempeh, Hyla-Louise Kluyts, Akinyinka Omigbodun, Adesoji Ademuyiwa, Muhammed Elhadi, Mohamed Elfagieh, Bernard Mbwele, Mpoki Ulisubisya, Lazaro Mboma, Daniel Z. Ashebir, Mahlet Tesfaye Bahta, Mohammed Hassen, Mikiyas Teferi, Yakob Seman, Eugene Zoumenou, Adam Hewitt-Smith, Janat Tumukunde, Dolly Munlemvo, Atilio Morais, Apollo Basenero, Pisirai Ndarukwa, Nazinigouba Ouerdraogo, Maman Sani Chaibou, Mohyeddine Zarouf, Ahmed Rhassane El Adib, Veekash Gobin, Zimogo Sanogo, Youssouf Coulibaly, Zipporah Ngumi, Tarig Fadalla, Cynthia Iradukunda, Vénérand Barendegere, Isaac O. Smalle, Mustapha Bittaye, Ahmadou Lamin Samateh, Mahmoud Elfiky, Maher Fawzy, Wakisa Mulwafu, Vanessa Msosa, Lygia Lopes, Akwasi Antwi-Kusi, Hamza D. Sama, Patrice Forget, Rupert M. Pearse, Marichen Puchert, Kris Schwebler, Freddy Kabambi, Tebogo Mabotja, Leandys Cobas, Albino Freitas, Maria Antunes, Bartolomeu Cabo, Domingos Paulo, Carlos Camongua, Yvette Avognon, Osseni Marcos, Raymond Kintomonho, Onesime Demahou, Gisèle Hounsa, Hugues Chobli, Elie Fassinou, Aurore Zoglobossou, Blaise Tchaou, Charles Tchegnonsi, Fifame Amadji, Francine Bossa, Ernest Ahounou, Djima Alao, Roushdane Odérémi, Afissatou Montairou, Oswald Gbehade, Romaric Tobome, Adam Boukari, Patrick Bakantieba, Arouna Sambo, Fanou Lionelle, Nounagnon Gilbert, Julien Attinon, Roger Klikpezo, Aumar Dadjo, Dénis Fanou, Gilberte Hounkpe, Bachabi Fafana, Néné Nguilu, Bodourin Dossou-Yovo, Chantal Segla, Mohamed Toko, Evelyne Gnele-Dedewanou, Michel Noukounwoui, Ethienne Yado, Timothé Gouroubéra, Valéry Adjignon, Serge Mewanou, Aïcha Tchomgang, Urielle Agossou, Fernand Soton, Charbel Azanlin, Lidwine Zomahoun, Rawéléguinbasba Armel Flavien Kabore, Salam Savadogo, Fatou Fleur Rosine Sanou, Farid Belém, Victoria Hien, Cheik Tidiane Hafid W. Bougouma, Sie Ahmed Ouattara, Mariam Bambara Kabore, Ouedraogo Nazinigouba, Papougnezambo Bonkoungou, Martin Lankoandé, Mireille Traoré, Patrick Sawadogo, Inès Wenmenga, Boureima Kinda, André Simporé, Christian Sapo, Salah Idriss Traore, Haoua Dipama, Lydie WR. Kaboré, Salifou Napon, Télesphore G. Kaboré, Arouna Louré, Pélagie PP. Tondé, Christian Zoundi, Martin Lankoande, Harouna Sanou, Remy Ndikumana, Carlos Nsengiyumva, Gregory Sund, Alliance Niyukuri, Axel Kwizera, Jean-Claude Niyondiko, Adolphe Manzanza Kilembe, Jean Pierre Mwema Ilunga, Nehema Hailemariam Sarah, Gabriel Mubobo Makeya, Idesbald Mwebe Mwepu, Ted Botawaosenge Likongo, Richard Kapela Mvwala, Raphael Nzau Kapend Mubunda, Noellie Kanka Mukuna, Julie Djondo Pembe, Nicolas Lumuanga Ndaye, Eric Bibonge Amisi, Mike Ilunga Madika, Joe Kembo Lungela, Didier Ndonda Mayemba, Philomene Mamba Diyoyo, Alex Mbo Ngalala, Martin Mamba Mukenga, Patricia Tito Kabuni, Dany Bolimo Mpoto, Herve Inesnku Mole, Louise Keby, Oria Andavo Buti, Anselme Phaka, Belinda Mayenge, Jean Jeacques Kabuley Kalongo, Timothe Kemfuni Mawisa, Rodrigue Tondo Ngwizani, Kuyala Leya, Dieudonne Kisile Sanduku, Timothe Nkemfuni Mawisa, Coco Nseke Mfumu, Mbuta Bolenge, Desire Kinzenzengu Kabuce, Patrick Kintieti, Amelia Mbuluku, Vicky Mahuwa, Tharcice Khonde Mabiala, Guilain Ngoy, Patrick Boloko, Nono Mazangama Mvwama, Jose Kengbanda, Pitchou Mushimbonga, Blaise Kuhapala, Nzosani Marcel, Kienze Guylain, Gerard Mboma, Sandra Zalambo Sagboze, Michel Muteya Manika, Jean Pierre Mumbere Kigayi, Roger Mukanire Cishugi, Placide Buhendwa Mugisho, Roger Baguma, Moïse Kongolo, Michel Mandungu Mbayabu, Crispin Mukendi Muamba, Edmond Banema Kapinga, Vasco Ngolela Kapinga, Guylain Tshimanga Nsumpi, Patrick Kanda Odia, Salomon Bingidimi, Gilbert Kpengbemale, Desire Hubert Bofunga Bosonga Imposo, Patricia Matondo, Servet Lelo, Jeremie Kalambayi, Mohamed Abdel-Ghaffar, Abdelrahman Soliman, Mostafa Abdelrahman, Sameh Shehata, Alia Rabee, Mohamed Abou Heba, Mohamed Rabei Abdelfattah, Tamer Ahmed Maher Ghoniem, Sherif M.K. Shehata, Mohamed Lotfy, Ahmed ElHaddad, Bereket Gebremeskel, Girmay Fisseha, Mebrahtu Abay, Degena Bahrey, Assefa Hika, Abdurezak Ali, Kindie Moges, Jemal Ahmed, Desalegn Abdisa, Abebe Megersa, Wendwosen Abayne, Haftom Berhane, Reiye Esayas, Fitsum Kifle, Kokeb Desita, Abebe Addise, Dagim Shimelash, Shitalem Tadesse, Bezaye Zemedkun, Peniel Kenna, Ayenew Yirdie, Abinet Sisay, Tebikew Gashu, Fassil Mihretu, Yesuf Ahmed, Bekele Debebe, Abdureuf Misgea, Amare Agmas, Rahel Assefa, Abdurahman Gelmo, Seifu Alemu, Brook Damtachew, Merid Mersha, Yaekob Chemere, Samuel Fekadu, Sintayehu Regasa, Bonsa Sileshi, Desalegn Wosen, Rebira Adamu, Gersam Mulugeta, Teshome Bacha, Zewude Gudisa, Kebebe Bekele, Alelign Tasew, Habtamu Gezahegn, Daniel Atlaw, Damtew Solomon, Habtemariam Gebresillasie, Girmaye Tesfaye, Negussie Sarbecha, Biniyam Sahiledengle, Kenbon Seyoum, Gemechu Ganfure, Yohannes Tekalegn, Gosa Tesfaye, Temesgen Ayichew, Shibiru Sendaba, Musefa Redwan, Eyasu Muse, Girma Nina, Bizuneh Sime, Addisalem Tadege, Anbesse Jima, Nugusu Ayalew, Dagmawi Workneh, Daniel Teferi, Momodou T. Nyassi, Landing N. Sanyang, Omar Jallow, Abdoulie Keita, Kitabu Jammeh, Charles Roberts, Patrick Idoko, Kebba Marenah, Masirending Njie, Musa Marena, Karamba Suwareh, Simon Boissey, Fatoumatta Jarjusey, Awa Jah, Awa Sanyang, Dado Jabbi, Kajali Camara, Armando Correa, John Jabang, Lamin Jaiteh, Lamin Dampha, Aminata Manneh, Baboucarr Sowe, Abdoulie Bah, Edrisa Jawo, Victoria Okoje, Momodou Baro, Yaya Bah, Mustapha Njie, Sainabou Mbowe, Ebrima Kanteh, Sarjo Ceesay, Alagie Manneh, Evans Atito-Narh, Adwoa Wilson, Romeo Hussey, Emmanuel Okine, Jemima Kwarteng, Ridge Ntiamoah, Samuel Dadzie, Mark Aseti, Naa Sowah, Akosua Appiah, Charles Bankah, Patrick Mburugu, Thomas Chokwe, Patrick Olang, Vernon Gacii, Susane Nabulindo, Antony Gatheru, Timothy Mwiti, Caroline Mwangi, Julius Muriithi, Daniel Ojuka, Omondi Ogutu, Evans Masitara, Mohamed Chaudhry, Reuben Kamundi, Annmarie Kangangi, Thomas Massaquoi, Stephen Takow, Felister Moraa, Aziz Munubi, Moses Kimani, Adili Wobenjo, Linda Nguu, Vincent Omeddo, Rose Malaba, Ambrose Nabwana, Anita Mwancha, Alexandria Mugaa, John Wamwaki, Joyce Chege, Seymour Sinari, Andrew Ndonga, Rose Shitsinzi, Walter Akello, Winfred Kimani, Elisha Kirwa, Seno Saruni, Andrew Wainaina, Ernest Nshom, Aidah Kenseko, Kizito Shisanya, Purity Wanjiru, Julliah Cherotich, Judy Kimutai, Benson Wahome, Grace Wangui, Dennis Wamalwa, Stephen Mwangi, John Chege, Tabitha Wanjiku, Carolyne Njoki, Wachira Waititu, Conrad Ambani, Samuel Murimi, Sharon Waithira, Nilson Mouti, Collins Kibet, John Kibet, Virginia Sokobe, Beatrice Jeymah, Antony Kamadi, Faith Gichuri, Steve Moses, David Wasike, Favours Adeya, Caesar Bitta, Stephen Ogendo, Killian Kariuki, Hdaya BenAbdalla, Taha Suliaman, Fatima Ali Abokhzam, Mohaned Isa, Mohammed Huwaysh, Asma Bourawi, Kais Alzubaidy, Mohammed Albaraesi, Sumayyah Bahroun, Abdulmueti Alhadi, Ahmed Msherghi, Amira Mohamed, Ala Khaled, Nouran Aljadi, Elham Bareig, Khaled Elgazwi, Adel Elgazwi, Ibrahim El-busife, Safa Owhida, Almahdi Eltwati, Samah Elakeili, Taha Abubaker, Fatima Elkhfeefi, Soha Younis Hasan, Amal Alttaira, Imbarkah Elmraied, Rim Wishah, Omar Abugassa, Hazem Ahmed, Amera Ellafi, Shoukrie Shoukrie, Nawal Aldokali, Aws ElGammudi, Akram Alkaseek, Hoda Elhaddad, Ayyah Alqaarh, Ahlam Brish, Malek Abudsnnuga, Salsabil Albuaishi, Mohammed Albashri, Marwa Morgom, Mohammed Alawami, Eman Shawesh, Abdullah Almabrouk, Moaz Alwarfalli, Nagia Abeid, Anis Buzreg, Ans Malek, Ameerah Abayu, Butaina Abdulhafith, Wedad Abouruwes, Marim Albakuri, Sabria Almuammari, Esam Alsaghair, Fatheia Alreshi, Hassan Badi, Rabiee Alfetoey, Naji Zubia, Bushray Almiqlash, Abdulsalam Alshuhoumi, Rayet Al-islam Ben Jouira, Amaal Dier, Essra Gebril, Mohammed Abdelkabir, Sana Moussa, Marwa Alfitori, Mabroukah Azbeda, Hajar Alamin, Ejmeya Barka, Omlsaad Mosbah, Rema Abdasalam, Miftah Hiyoum, Maryam Abd allateef, Ibrahim Altomi, Mahdi Alsakloul, Ekhlas Karami, Munyah Alriqeeq, Mabruka Omar, Ashraf Samer, Aml Aemeesh, Ahmad Bouhuwaish, Ahmed Elusta, Sultan Ahmeed, Wesal AlFighi Hassan, Mouadah Ali Altayr, Mohamed Addalla, Abrar Geddeda, Kheria Khoja, Doaa Alhaj, Muaad Etturki, Ahmed Elhadi, Ibrahim Ellojli, Anshirah Shuwayyah, Ahmed Elfaghih, Malak Alduwayb, Mohamed Aleiyan, Wedad Aboubreeq, Soliman Alkassem, Sami Ashour, Hayat Ben Hasan, Najat Ben Hasan, Ali Yahya, Palesa Chisala, Edward Kommwa, Lusayo Simwinga, Agness Chalira, Precious Kachitsa, Onias Mtalimanja, Drissa Traoré, Moussa Sissoko, Moussa Camara, Adama Koita, Sekou Koumaré, Omar Sacko, Mahamadou Coulibaly, Lamine Soumaré, Soumaïla Keita, Sidiki Keita, Hamadoun Dicko, Boubacar Diallo, Boureima Bengaly, Mohamed Keita, Siaka Diallo, Drissa Ouattara, Nouhoun Ongoiba, Seydina Beye, Honoré Berthe, Mamadou Diakite, Mamadou Sima, Adégné Togo, Bakary Dembele, Djibo Diango, Moussa Samake, Youssouf Traoré, Louis Traoré, Ongoïba Oumar, Sogoba Gaoussou, Issaga Traoré, Sidy Sangaré, Doua Kanté, Lassana Cissé, Thiam Souleymane, Keita Koniba, Sundaresan Maiyalagan, Julien Chong, Adil Mohit, Khushyant Mungar, Shankaran Vinayagam, Kevin Ramlochun, Jamie Sim, Desai Sneha, Vishaal Kissoon, Yan Tseung, Mohamed Aboobakar, Nitish Fokeerah, Ravi Ramsewak, Jayprakash Gopall, Meetheelesh Abeeluck, Varun Seewoo, Divyanand Jankee, Ashveen Puryag, Senthil Beemadoo, Yashraj Deenoo, Abhisek Goureah, Munawwara Makoon, Hemanshu Rambojan, Beeharry Shanjugsingh, Kevin Viraswami, Shehzaad Joomye, Ashwant Bhugwandass, Bibi Deelawar, Vakil Leelodharry, Luckshmanraj Mungur, Sajid Aungraheeta, Sirsingh Bhajoo, Manpreet Rajcoomar, Rishi Seetaram, Subha Gaya, Gini Batra, Yoshvin Sunnassee, Shailendra Petkar, Sbai Hicham, Labib Smail, Ait Laalim Said, Motaai Youssef, Mouhssine Doumiri, Mustapha Alilou, Nora Farnaoui, Mustapha Bensghir, Abdelghafour Elkoundi, Abdelhamid Jaafari, Abderhmann Elwali, Mohammed Meziane, Walid Atmani, Houssam Rebahi, Hajar Chichou, Safae Zarouf, Abderraouf Soummani, Abou Elhassan Taoufik, Meryem Essafti, Aminata Oumou Traoré, Hamzaoui Hamza, Adnane Berdai, El allani Linda, Salhi Oussama, Nelson Mucopo, Machado Banze, Mouzinho Saide, Tomas Sitoi, Artur Machava, Antonio Carlos, Amilton Guidione, Antonio Saide de Carvalho, Natacha Gemo, Samiro Sema Camal, Arsénio Cuna, Ornelos Madeira, Ladino Assuade, Dercio Amde Fernandes, Dulce Alexandre Machavae Fernandes, Mandua Sebastião, Bernard Sikombe, Matti Kandjimi, Ayoub Shekimweri, Diana Shilomboleni, Mbaundju Kandjii, Leonard Kabongo, Cholastic Hangero, Ike Ndjoze, Ruben Nailonga, Immanuel Uukonga, Uutoni Nakanyala, Lavinia Johannes, Adrian Haruzuvi, Chris Terblanche, Natangwe Shimenda, Delwina Katjipu, Hilma Shalimba, Juliah Kaweendwa, Ali Mbuyi, John Oyedele, Mapumba Mulolo, Peter Njuki, Mutombo Ndaie, Akutu Munyika, Hilma Katangolo, David Tjiyokola, Tawanda Mhene, Archbald Masiambiri, Paidamoyo Mandudzo, Sandra Kapepiso, Haziel Mavesere, Cedia Tjihoto, Daylight Manyere, Charlotte Kauraisa, Learnmore Garanowako, Michael Tune, William DeKlerk, Benvenue Ndolo, Maria Angula, Ndapewoshali Hishekwa, Elizabeth Nandjendja, Elsabe Tsauses, Eunice Mouton, Kudzai Katandawa, Sophia Bruwer, Jaydee Van Staden, Beata Siteketa, Beata Kaholongo, Martha Ntinda, Pueya Nashidengo, Johanna Kandjumbwa, Lahia Lipumbu, Moussa Sirfi, Fouma Djibo, Moutari Mahaman, Abdoulaye Mahaman Bachir, Maikassoua Mamane, Adakal Ousseini, Maman Noury Hamissou Souley, Rabo Oumarou, Rekia Idrissa, Moussa Ichaou, Amina Saley, Abdoulay Seyni, Sahabi Amadou, Mahamane Sani Mahamane Laminou, Issoufou Moustapha Camara, Moussa Gagara, Hadjara Rabiou Daddy, Harissou Adamou, Ibrahim Amadou Magagi, Oumarou Habou, Sabo Ramatou, Saidu Kadas, Rabiu Mohammed, Abubakar Ballah, Tella Olalekan, Kefas Bwala, Mohammed Adamu, Adamu Isa, Ademola Adeyeye, Samuel Fayose, Akinola Akinmade, Taiwo Ajayi, Elizabeth Nwasor, Saidu Yakubu, Euphemia Ugwu, George Mukoro, Muhammed Ahmed, Gideon Akafa, Ahmad Lawal, Daniel Nwoye, Michael Odigbo, Zulaihatu Sarkin-Pawa, Tunde Sholadoye, Benjamin Fomete, Hamisu Yakubu, Abdulkadir Kabiru, Samaila Timothy, Ali Yusuf, Tasiu Saadu, Babangida Mohammed, Abdulghaffar Yunus, Ganiyat Olagunju, Muhammad Aminu, Mohammad Idris, Musliu Tolani, Nasiru Dalhat, Samuel Gana, Talent Adike, Lofty-John Anyanwu, Abdurrahman Sheshe, Sani Aji, Mamuda Atiku, Raphael Attah, Abubakar Muhammed, Rasaki Oseni, Halima Salisu-Kabara, Benjamin Nkemjika, Omotayo Salami, Adekunle Akadri, Bukola Olayinka, Clement Onuoha, Umar Usman Jamaare, Auwalu Saminu Jibrin, Sani Giade Abdullahi, Ibrahim Ishaku, Adenike Odewabi, John Bamigboye, Oladapo Kuforiji, Chidiebere Ogo, Stella Ogunmuyiwa, Abdussemee Abdurrazzaaq, Adebayo Tanimola, Michael Adeyanju, Oluwatimilehin Andero, Temitope Ojo, Olusi Adedotun, Gbadamosi Kehinde, Jimoh Buraimoh, Kabiru Muhammad, Sophia Baidoo, Patrick Okoli, Azeez Adigun, Ekene Ezeonye, Kabir Isa, Yetunde Aremu-Kasumu, Kamil Shoretire, Peter Enesi, Amechi Ezike, Olatunde Olawoye, Emmanuel Ugwu, Christopher Ukah, Abolade Olugbenga, Nwachukwu Chidiebere, Nasiru Abdulraman, Adebiyi Olusegun, Alisa Halisa, Semiat Yusuf, Jamila Salisu, Chidiebube Okoro, Abdul Suleiman, Fabian Onowighose, Aliyu Farinyaro, Suleiman Baba, Umar Abdulmajid, Aisha Abdurrahman, Ogochukwu Obi, Olatunde Alabi, William Adeyemi, Jelili Salau, Jones Taiwo, Nnaemeka Nwafulume, Taiye Ibiyeye, Edith Agu, Ayodeji Danboy, James Abdulazeez, Christopher Ekwunife, Chimaobi Nnaji, Chigozirim Onyekpere, Amara Arunsi, Jude Egwim, Obianuju Nwana, Nnabuike Ojiegbe, Charles Mbamba, Paul Ngwu, Frank Imahigbe, Emmanuel Okoroji, Iloh Ikenna, Abdulrahman Mohammed, Adebayo Adeniyi, Toluwalope Ariyo, Olajide Gabriel, Tesleem Orewole, Salawu Idris, Idowu Adebara, Abiodun Okunlola, Akinwale Akinbade, Oluwasesan Afolabi, Adewumi Bakare, Olabisi Adeyemo, Benjamin Ugwu, Samuel Nuhu, Henry Embu, Erdoo Isamade, Chinedu Obikili, Amaka Ocheke, Solomon Peter, Donald Orshio, Peter Onuminya, Jack Okopi, Olufemi Bankole, Bosede Afolabi, Dapo Osinowo, Ayodeji Oluwole, Muyiwa Rotimi, Ibironke Desalu, Rufus Ojewola, Bolaji Mofikoya, Kola Owonikoko, Adeolu Adeoye, Temidayo Bobo, Taiwo Akinloye, David Ama, Ebere Okoronkwo, Muhammad Mahmud, Jamiu Adebiyi, Temitope Babalola, Mansur Muhammad, Afeez Aruna, Maryrose Osazuwa, Ayodeji Yusuf, Isiaka Lawal, Bitrus Fidelis, Rephath Pius, Cyril Jomosu, Adebayo Adedayo, Abubakar Aliyu, Adaora Agholor, Abdullateef Abdulazeez, Chabiya Bala, Eziamaka Eze, Elizabeth Ani, Uchenna Okeke, Dominica Adebayo, Okechukwu Ekwunife, Victor Modekwe, Chuka Ugwunne, Chukwuemeka Okoro, Chisom Uche, Simeon Olateju, Fred Ige-Orhionkpaibima, Adedapo Adetoye, Olurotimi Aaron, Jeremiah Abimbola, Folayemi Faponle, Olumuyiwa Ajayeoba, Olusoji Jagun, Oluwabunmi Fatungase, Adeniyi Akiseku, Chigbundu Nwokoro, Ramotalai Shoyemi, Ibukunolu Ogundele, Nankat Joseph, Salihu Bura, Chukwuka Nwezoku, Manu Bwala, Meshach Philips, Abubakar Usman, Emmanuel Filibus, Zara Umate, Nwabuoke Chukwuka, Ahmed Nuhu, Watakiri Ibrahim, James Nggada, Ali Izge, Musa Ismail, Olayinka Eyelade, Tinuola Adigun, Babatunde Osinaike, Olayinka Ogunbode, Olusola Idowu, Taiwo Lawal, Temidayo Ogundiran, Olayiwola Shittu, Omobolaji Ayandipo, Stephen Edino, Zumnan Songden, Olumide Akitoye, Bissallah Ekele, Godwin Akaba, Terkaa Atim, Akitoye Adeleke, Owoicho Okochi, Sunday Akeju, Ernest Ukpoju, Osayomwanbo Osaheni, Ifunanya Obaseki, Lateef Kehinde, Osawemwenze Monday, Stanley Nte, Adesuwa Agboifo, Omajuwa Dawodu, Precious Orhiere, David Atiti, Queeneth Kalu, Felix Effiom, Israel Kolawole, Olawale Ojo, Afusat Olabinjo, Olufemi Ige, Beatrice Ogunyemi, Olusola Oladosu, Kikelomo Adesina, Sulaiman Agodirin, Asimiyu Shittu, Audu Idrisa, Sadiq Adamu, Nuhu Ali, Olayinka Adewunmi, Stephen Nwankwor, Akinwumi Olakanmi, Oluseye Ajayi, Ayotolu Ajayi, Victor Ogunmola, Oluwafunke Olakanmi, Adam Kuranga, Enoch Uche, Chukwuemeka Osuagwu, Chukwudi Ilo, Mesi Matthew, Uko Uko, Ngozi Mba, Olubusola Alagbe-Briggs, Amabra Dodiyi-Manuel, Bisola Onajin-Obembe, Bright Obasuyi, Richard Echem, Ihuoma Mike-Elechi, Job Otokwala, Mark Edubio, Catherine Eyo, Isaac Udo, Aliyu Abdulrahman, A.A. Abdullahi, Ibrahim Galadima Bello, Usman Adinoyin Mohammed, Abidemi Oyaromade, Mohammed Bello, Usman Muhammad, Emeri Mbah, Hyacinth Okereke, Almustapha Aminu, Anthony Ahmadu, Abu Rogers, Peter Samai, Sao Amara, Margaret Yankuba, Mary Josayah, Jayah Swarray Jnr, Alusine Dawo, Peter George, Mustapha Kabba, Mohamed Bah, Charles Mondeh, Ibrahim Kapuwa, Mohamed Sheku, Philip Mattia, Brima Sesay, Jones O.A. Omoshoro-Jones, Motselisi Mbeki, Estie Cloete, Philip Anderson, Busi Mrara, Annemarie Steyn, Tsakani Mhlari, Nic Proctor, Caroline Robertson, Gillian Lamacroft, Usha Singh, Sebenzile Sikhakhane, Kelly Gate, Shepherd Nzenza, John Tshimbalanga Kasonga, Sibongile Ndebele, Patrick Lufuta Kande, Jody Davids, Tino-vito Orlandi, Marischka de Jong, Hugo Stark, Francois Roodt, Jonathan Hall, Ian Nortje, Akanimo Akpakan, Vishendran Govindasamy, Ronisha Sathiram, Mohammad Kathrada, Zane Farina, Lucio Frittella, Charles Kohler, Sibuyiselwe Lubelwana, Sarwat Ikram-Hameed, Adriaan Smit, Muneerah Cassiem, Yvonne Freeman, Saaliha Goga, Larissa Cronje, Constantin Buzdugan, Subash Chirkut, Priyadeshni Singh, Sandhya Jithoo, Vivesh Rughubar, John Arnold, Rishan Bipath, Suman Mewa Kinoo, Ncumisa Khanyisa Msolo, Fleur Ackermans-Deijnen, Tshegofatso Mmasello Emma Boka, Martyn Biccard Greenwood, Shakthi Anand Jayrajh, Devarani Naidoo, Syndrini Reddy, Devandiran Harriraman Rungan, Kylene Subrayen, John Roos, Nina Tredoux, Pascal Plumacher, Anthony Reed, Harald Steinhaus, Mariesa Nock, Paul Ryan Herselman, Gareth Davies, Talitha Harvey, Franklin Muller, Willem Naude, Tania Pretorius, Johan Jochemus Swart, Merryn Walls, Prashant Gokal, Nicolette Rorke, Farzaana Dhoodhat, Precious Dzanibe, Mohammed Yusuf Hussain, Ashmita Junpath, Ameela Maharaj, Hylda Makanisi, Khalid Moosa, Ting Ting Wong, Sean Mould, Trisha Ramsamy, Roel Matos-Puig, Hayley Morgan, Nadeem Nabeebuccas, Ria Devi Naidoo, Viantha Pather, Vasheel Vasheel Bahadur, Renilda Pillay, Zahnne Fullerton, Nicole Bell, Bongisa Grey, Vincent Lorenzo Visentin, Hendrik Adriaan Van Zyl, Terri Anne Killingbeck, Emile Maneveldt, Gerhard Thiart, Magdelena May Venter, Oostewalt Swart, Mariette Grobelaar, Carel Cairns, David Bishop, Christien Steenkamp, Thandekile Khumalo, Noel Naidoo, Ross Murray, Martin Kopieniak, Melusi Sishange, Mxolisi Brian Ndimande, Megan Jaworska, Sarwat Ikram, Bence Rainier, Renier J. Liebenberg, Helena D. Zwiegers, Philip M. Nortje, Kamal Bhagwan, Margot Flint, Robert Dyer, Simone Adams, Yoshua Bwambale, Danny Ngomo, Patrice Kanku, Nivashen Pillay, Alexa de Castro, Atisha Maharaj, Janine Carim, Jenna Leigh Taylor, Karl M. Köhne, Leanne W. Drummond, Leanne Temlett, Lieze Geldenhuys, Yvonne Seilbea, Kathryn Naidoo, Nicola A. Kalafatis, Stefné Verwey, Thulile Biyase, Theroshnie Kisten, Belinda S. Kusel, Timothy Craig Hardcastle, Richard Magagula, Christian Kampik, Kuzolunga Xulu, Sivuyisiwe Solala, Mia Sayed, Basil Enicker, Anil Madaree, Innocent Mukama, Gladmore Madombwe, Nonhlanhla Zulu, Nompumelelo Gasa, Nokuzula Kanjana, Sebenzile Buthelezi, Thembelihle Buthelezi, Andries Brink, Francois Potgieter, Busisiwe Mrara, Zaynab Alexander, Charles Choto, Paula Ima, Zintle Gxagxisa, Baphethuxolo Ningiza, Gillian Lamacraft, Jerome Mogorosi, Nadia du Plessis, Leonie de Man, Suné Thompson, Gerrit van Heerden, Edwin W. Turton, Pieter M. van der Linde, Josephine K. Teme-Pitse, Reitumetse Tladi, Gillian D. Saffy, Ene-Mari Roscher, Kristel Fortune, George Barnard, Tiisetso Makhasane, Evan Bowen, Akangcha Pal, Rachel Moore, Maria Fourtounas, Mary Augusta Adam, Renessa Arumugan, Gabriella Hyman, Jaclyn Jonosky, Maninginingi Makondo, Heveshan Moodley, Phillip Munda, Mzwandile Nyalungu, Victor Olusola, Sohan Zane Pinto, Tristan Pillay, Lucinda Singh, Paul Mwindekuma Wondoh, John Devar, Boitumelo Baloyi-Mnisi, Zach Koto, Matlou Ernest Mabitsela, Sibongile Ruth Ndlovu, Branny Mthelebofu, Colin Beck, Matthew Dold, Alice Fan, Shannon MacQueen, Thembani Matabata, Catherine Mpehle, Charné Kulenkampf, Tsakani McCreath Mhlari, Simangele Cecilia Nyoka-Mokgalong, Felix Thumba Masinge, Randhir Ramnath Gunpath, Maropeng Petrus Pat Mothwa, Jo-Anne Asenath Mothwa, Danai Mhlanga, Jamie-Lyn Colly, Aunel Mallier Peter, Khalid Ben Hameda, Pulane Mokae, Stella Josephine Moumakoe, Kelechi Ekeh, Nezingu Lengo, Marnus Booyens, Inge Louise Seale, Pieter Daniel Theron, Nicolaas Abraham Schuman, Amber Carlyn Sonn, Jacobus Lukas Stander, Nadia Cloete, Marius Cloete, Catherine Ann Makepeace, Ronel van der Westhuizen, Leanne Robyn Messiahs, Amy Ruth Visagie, Fatima Vawda, Frans Christiaan Voster, Deepika Dhilraj, Oliver Smith, Stefan Bolon, Daniel Montwedi, Motsilisi Mbeki, Jayde Wyngaard, Mthunzi Ngcelwane, Thomas Kleyenstuber, Phyllis Phukubye, Liesel Schärf, Grace Laker, Elizabeth Semenya, Reinhard Dembskey, Thomas Tarlton, Tapiwa Jiri, Ngoie Hubert Mushid, Nhlanhla Samuel Ngwenya, Hazel Morongoa Mogodi, Carmen Sinevici, Anthony Osarogie Usenbo, Naledi Fodo, Anesu Chimini, Ntetelelo Sikobi, Sinovuyo Nokwange, Mluleki Noqhamza, Qumba Thembisa, Kajake Anantha Padmanabha Bhat, Rabin Mathew, Katrin Middleton, Abdus-sami Adewunmi, Craig Dickson, Humairah Bulbulia, Bianka Bester, Michelle de Klerk, Christia Benade, Francois Viljoen, Monique Fischer, Khalid Alfaki, Abdalmalik Awad, Abdelsalam Algray, Mohammed Elsiddig, Suha Mohamed, Salih Mahmoud, Muhammed Osman, Asia Elgailany, Mazin Suliman, Hanaa Mohammed, Lina Aljeally, Mohammed Dirar, Mohammed Osman, Mazin Mohamed, Mohamed Elhasan, Abrar Widatalla, Abubakr Abubakr, Eman Mohamed, Alshareef Nour, Ntonto Doris Gama, Dolorosa Khetsiwe Shabangu, Cynthia Iradikunda, Samuel Mkoko, Paul Kisanga, Emmanuel Lema, Benson Lyimo, Mohamed Binde, Alphonce Chandika, Salim Salim, Sylvia Jumbe, Abel Makubi, Vihar Kotecha, Felician Kachinde, Museleta Nyakiroto, Emmanuel Jitambi, Venant Geofrey, Johaphes Josiah, Phinius Makubi, Frank Manumbu, Suzan Mlingwa, Ernest Ibenzi, Peter Mbelle, Kato Peleus, Enid Chiwanga, Nillah Richard, Shoo Leonard, Paulo Sanka, Subira Mushi, Bashir Nyangasa, Mohamed Janabi, Naizihijwa Majani, Pedro Palangyo, Evarist Nyawawa, William Ramadhan, Faraj Lydenge, Gileard Gabriel Masenga, Sakina Rashid, Mubashir Jusabani, Ansbert Ndebea, Jenitha Cheru, Margaret Henjewele, Greyson Kilimanjaro, Sarah Sikimata, Deocles Donatus, Hazina Maduhu, Tumaini Mariro, Given Massasi, Moshi Moshi Shabani, Braison Cholela, Marco Mgeleka, Yohatinus Mbilinyi, Faraja Chiwanga, Bilton Exavery, Caspar Haule, Samson Ndile, Sirili Harya, Julieth Magandi, Deogratius Manyama, Redempta Matindi, Adam Moshi, Daudi Kitwana, Merida Makia, Philip Muhochi, Miriam Herman, Clauda Miombo, Furaha Kahindo, Langtone Kishebuka, Elijah Ussiri, Gloria Kinasa, Patrick Adel, Eric Malaba, Vensesla Sakwari, Sadot Lugereka, Mohamed Mungia, George Mocha, Herman Wella, Cecilia Protas, Patrick Karua, Ahmada Kashagama, Faraja Mwasambugu, Suzana Kajeri, Jacquiline Mchilla, Elibariki Lucumay, Robert Maise, Amon Marti, Beatrice Mahundi, Frederika Jager, Charles Majani, Ludovick Rukeha, Tareeq Mohamed, Nabila Fuad, Winifrida Halinga, Elias Chrisant, Gilbert Msoma, Titus Kihwili, Gadiel Temu, Naima Yusuf, Rashid Saleh, Rashid Inoja, Eva Shang'a, Stella Ibrahim, Hussein Msuma, Edwin Edward, Paul Kilamile, Stephen Mwakyolile, Talkana Adja, Edem Gueouguede, Hafoudhoi Oussene Seddoh, Saliou Adam, Pilakimwe Egbohou, Mawunyo Ahomagnon, Olivier Kadjossou, Abdul-Bassiti Boukari, Mary T. Nabukenya, Ruth Muhindo, Peter Waswa, Peter Kaahwa Agaba, Daphne Kabatoro, Joseph Kayongo, Margaret Naggujja, Nabasiige Rehema, Phiona Nansubuga, Daniel Kavuma, Aggrey Lubikire, Hope Bisilikirwa, Godfrey Ssebaggala, Emmanuel Muwema, Humble Joan Agaba, John Kiconco, Nicholas Wataaka, Bonet Chan, Mary Juliet Nampawu, Fred Bulamba, Emmanuel Bua, Christine Mugala, Caroline Nyakato, John Paul Ochieng, Linda Kyomuhendo Jovia, George Kateregga, Rachel Alum, Lazia Najjuma, Gorret Nampiina, Andrew Kintu, Joshua Sempiira, Luzige Simon, Peter Kayima, Jacob Eyul, Erick Odwar, Rita Nkwine, Christine Namata, Elizabeth Nabakka, Denis Kakaire, Velda Mushangwe-Mtisi, Erisha Munhamo, Celestino Dhege, Juliet Hungwa, Hemish Jasi, Crispin Ntoto, Derek Matsika, Brightson Mutseyekwa, Joseph Zimbovoora, Beaulah Gudyanga, Dennis Mazingi, Chenesa Mbanje, Busisiwe Mlambo, Michael Chiwanga, Harunavamwe N. Chifamba, Sarudzai Zhou, Esta Hove, Shamiso Dende, Beauty Manjengwa, Penias Kapisa, null Mashava, Caritas Chiura, Locadia Katsukunya, Godfrey Muguti, Doreen Mashava, Elton Ndhlovu, Zanele Mangwangwa, and Nombulelo Dube

Subjects
medicine.medical_specialty, Interprofessional Relations, media_common.quotation_subject, Psychological intervention, Fidelity, Postoperative Complications, Surveys and Questionnaires, Intervention (counseling), Humans, Medicine, Postoperative Period, Cooperative Behavior, Nursing management, media_common, Response rate (survey), business.industry, Standard of Care, Odds ratio, Hospitals, Confidence interval, Clinical trial, Anesthesiology and Pain Medicine, Population Surveillance, Africa, Physical therapy, business
Abstract

Background The African Surgical OutcomeS-2 (ASOS-2) trial tested an enhanced postoperative surveillance intervention to reduce postoperative mortality in Africa. We undertook a concurrent evaluation to understand the process of intervention delivery. Methods Mixed-methods process evaluation, including field notes, interviews, and post-trial questionnaire responses. Qualitative analysis used the framework method with subsequent creation of comparative case studies, grouping hospitals by intervention fidelity. A post-trial questionnaire was developed using initial qualitative analyses. Categorical variables were summarised as count (%) and continuous variables as median (inter-quartile range [IQR]). Odds ratios (OR) were used to rank influences by impact on fidelity. Results The dataset included eight in-depth case studies, and 96 questionnaire responses (response rate 67%) plus intervention fidelity data for each trial site. Overall, 57% (n=55/96) of hospitals achieved intervention delivery using an inclusive definition of fidelity. Delivery of the ASOS-2 interventions and data collection presented a significant burden to the investigators, outstripping limited resources. The influences most associated with fidelity were: surgical staff enthusiasm for the trial (OR=3.0; 95% confidence interval [CI], 1.3–7.0); nursing management support of the trial (OR=2.6; 95% CI, 1.1–6.5); performance of a dummy run (OR=2.6; 95% CI, 1.1–6.1); nursing colleagues seeing the value of the intervention(s) (OR=2.1; 95% CI, 0.9–5.7); and site investigators' belief in the effectiveness of the intervention (OR=3.2; 95% CI, 1.2–9.4). Conclusions ASOS-2 has proved that coordinated interventional research across Africa is possible, but delivering the ASOS-2 interventions was a major challenge for many investigators. Future improvement science efforts must include better planning for intervention delivery, additional support to investigators, and promotion of strong inter-professional teamwork. Clinical trial registration ClinicalTrials gov NCT03853824.

Published
2021
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40. Linking plant and vertebrate species to Nature's Contributions to People in the Swiss Alps

Author

Pierre-Louis Rey, Pascal Vittoz, Blaise Petitpierre, Antoine Adde, and Antoine Guisan

Subjects
Humans, Animals, Ecosystem, Switzerland, Plants, Vertebrates, Conservation of Natural Resources, Multidisciplinary
Abstract

Since the late 1990s, Nature’s Contributions to People (NCPs; i.e. ecosystem services) were used as a putative leverage for fostering nature preservation. NCPs have largely been defined and mapped at the landscape level using land use and cover classifications. However, NCP mapping attempts based directly on individual species are still uncommon. Given that species shape ecosystems and ultimately deliver NCPs, mapping NCPs based on species distribution data should deliver highly meaningful results. This requires first establishing a census of the species-to-NCP relationships. However, datasets quantifying these relationships across several species and NCPs are rare. Here, we fill this gap by compiling literature and expert knowledge to establish the relationships of 1816 tracheophyte and 250 vertebrate species with 17 NCPs in the Swiss Alps. We illustrated the 31,098 identified species-NCP relationships for the two lineages and discuss why such a table is a key initial step in building spatial predictions of NCPs directly from species data, e.g. to ultimately complement spatial conservation planning.

Published
2023

41. Characteristics of children ≤36 months of age with DIPG: A report from the international DIPG registry

Author

Allison L Bartlett, Adam Lane, Brooklyn Chaney, Nancy Yanez Escorza, Katie Black, Anne Cochrane, Jane Minturn, Ute Bartels, Kathy Warren, Jordan Hansford, David Ziegler, Blanca Diez, Stewart Goldman, Roger Packer, Mark Kieran, Mariko DeWire-Schottmiller, Craig Erker, Michelle Monje-Deisseroth, Lars Wagner, Carl Koschmann, Kathleen Dorris, Chie-Schin Shih, Tim Hassall, Yvan Samson, Paul Fisher, Stacie S Wang, Karen Tsui, Gustavo Sevlever, Xiaoting Zhu, Phillip Dexheimer, Anthony Asher, Christine Fuller, Rachid Drissi, Blaise Jones, James Leach, and Maryam Fouladi

Subjects
Cancer Research, Oncology, Child, Preschool, Humans, Brain Stem Neoplasms, Glioma, Registries, Neurology (clinical), Astrocytoma, Child, Pediatric Neuro-Oncology
Abstract

Background Children ≤36 months with diffuse intrinsic pontine glioma (DIPG) have increased long-term survival (LTS, overall survival (OS) ≥24 months). Understanding distinguishing characteristics in this population is critical to improving outcomes. Methods Patients ≤36 months at diagnosis enrolled on the International DIPG Registry (IDIPGR) with central imaging confirmation were included. Presentation, clinical course, imaging, pathology and molecular findings were analyzed. Results Among 1183 patients in IDIPGR, 40 were eligible (median age: 29 months). Median OS was 15 months. Twelve patients (30%) were LTS, 3 (7.5%) very long-term survivors ≥5 years. Among 8 untreated patients, median OS was 2 months. Patients enrolled in the registry but excluded from our study by central radiology review or tissue diagnosis had median OS of 7 months. All but 1 LTS received radiation. Among 32 treated patients, 1-, 2-, 3-, and 5-year OS rates were 68.8%, 31.2%, 15.6% and 12.5%, respectively. LTS had longer duration of presenting symptoms (P = .018). No imaging features were predictive of outcome. Tissue and genomic data were available in 18 (45%) and 10 patients, respectively. Among 9 with known H3K27M status, 6 had a mutation. Conclusions Children ≤36 months demonstrated significantly more LTS, with an improved median OS of 15 months; 92% of LTS received radiation. Median OS in untreated children was 2 months, compared to 17 months for treated children. LTS had longer duration of symptoms. Excluded patients demonstrated a lower OS, contradicting the hypothesis that children ≤36 months with DIPG show improved outcomes due to misdiagnosis.

Published
2022
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42. Childhood mortality during and after acute illness in Africa and south Asia

Author

Abdoulaye Hama Diallo, Abu Sadat Mohammad Sayeem Bin Shahid, Ali Fazal Khan, Ali Faisal Saleem, Benson O Singa, Blaise Siezanga Gnoumou, Caroline Tigoi, Catherine Achieng Otieno, Celine Bourdon, Chris Odhiambo Oduol, Christina L Lancioni, Christine Manyasi, Christine J McGrath, Christopher Maronga, Christopher Lwanga, Daniella Brals, Dilruba Ahmed, Dinesh Mondal, Donna M Denno, Dorothy I Mangale, Emmanuel Chimezi, Emmie Mbale, Ezekiel Mupere, Gazi Md. Salauddin Mamun, Issaka Ouedraogo, James A Berkley, Jenala Njirammadzi, John Mukisa, Johnstone Thitiri, Joseph D Carreon, Judd L Walson, Julie Jemutai, Kirkby D Tickell, Lubaba Shahrin, MacPherson Mallewa, Md. Iqbal Hossain, Mohammod Jobayer Chisti, Molly Timbwa, Moses Mburu, Moses M Ngari, Narshion Ngao, Peace Aber, Philliness Prisca Harawa, Priya Sukhtankar, Robert H J Bandsma, Roseline Maimouna Bamouni, Sassy Molyneux, Shalton Mwaringa, Shamsun Nahar Shaima, Syed Asad Ali, Syeda Momena Afsana, Syera Banu, Tahmeed Ahmed, Wieger P Voskuijl, Zaubina Kazi, APH - Health Behaviors & Chronic Diseases, APH - Global Health, Pediatrics, Network, The Childhood Acute Illness and Nutrition (CHAIN), Graduate School, Global Health, Amsterdam Gastroenterology Endocrinology Metabolism, and General Paediatrics

Subjects
Asia, Child, Preschool, Kwashiorkor, Acute Disease, Child Mortality, Aftercare, Humans, Infant, General Medicine, Prospective Studies, Child, Africa South of the Sahara, Patient Discharge
Abstract

Background Mortality among children with acute illness in low-income and middle-income settings remains unacceptably high and the importance of post-discharge mortality is increasingly recognised. We aimed to explore the epidemiology of deaths among young children with acute illness across sub-Saharan Africa and south Asia to inform the development of interventions and improved guidelines. Methods In this prospective cohort study, we enrolled children aged 2–23 months with acute illness, stratified by nutritional status defined by anthropometry (ie, no wasting, moderate wasting, or severe wasting or kwashiorkor), who were admitted to one of nine hospitals in six countries across sub-Saharan Africa and south Asia between Nov 20, 2016, and Jan 31, 2019. We assisted sites to comply with national guidelines. Co-primary outcomes were mortality within 30 days of hospital admission and post-discharge mortality within 180 days of hospital discharge. A priori exposure domains, including demographic, clinical, and anthropometric characteristics at hospital admission and discharge, as well as child, caregiver, and household-level characteristics, were examined in regression and survival structural equation models. Findings Of 3101 children (median age 11 months [IQR 7–16]), 1120 (36·1%) had no wasting, 763 (24·6%) had moderate wasting, and 1218 (39·3%) had severe wasting or kwashiorkor. Of 350 (11·3%) deaths overall, 234 (66·9%) occurred within 30 days of hospital admission and 168 (48·0%) within 180 days of hospital discharge. 90 (53·6%) post-discharge deaths occurred at home. The proportion of children who died following discharge was relatively preserved across nutritional strata. Numerically large high-risk and low-risk groups could be disaggregated for early mortality and post-discharge mortality. Structural equation models identified direct pathways to mortality and multiple socioeconomic, clinical, and nutritional domains acting indirectly through anthropometric status. Interpretation Among diverse sites in Africa and south Asia, almost half of mortality occurs following hospital discharge. Despite being highly predictable, these deaths are not addressed in current guidelines. A fundamental shift to a child-centred, risk-based approach to inpatient and post-discharge management is needed to further reduce childhood mortality, and clinical trials of these approaches with outcomes of mortality, readmission, and cost are warranted.

Published
2022
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43. Progress Update: Palliative Care Development Between 2017 and 2020 in Five African Countries

Author

Emmanuel Luyirika, Diederik Lohman, Zipporah Ali, Mackuline Atieno, Anna Mahenge, Paul Mmbando, Esther Muinga, David Musyoki, Mark Donald Mwesiga, Eve Namisango, Peter Nosim, Geoffrey Opio, Sara Pardy, Aimable Ruzima, Eva Skowronska, Blaise Uhagaze, Joyce Zalwango, and Aggrey Aluso

Subjects
Anesthesiology and Pain Medicine, Health Personnel, Hospice and Palliative Care Nursing, Palliative Care, Humans, Neurology (clinical), Delivery of Health Care, Kenya, General Nursing
Abstract

This article provides a progress update on the development of palliative care in five countries in Africa-Kenya, Rwanda, South Africa, Tanzania, and Uganda-between 2017 and 2021, and explores the role of palliative care advocates and the Open Society Foundations in this process.To provide a progress update on the development of palliative care in Kenya, Rwanda, South Africa, Tanzania, and Uganda between 2017 and 2021 and to examine the impact of twenty years of Open Society Foundations support for palliative care in the region on the integration of palliative care into publicly funded health systems.In the mid-2000s, palliative care pioneers in these five countries, supported by Open Society Foundations, began to train health care providers and engage policy makers to ensure that people with life-limiting illnesses and their families had access to appropriate services and essential medicines. In the late 2010s, it embraced an approach that mixed strategic communications and advocacy for inclusion of palliative care into universal health coverage with technical assistance.By the mid-2010s, a vibrant palliative care community existed that worked closely with governments to develop palliative care policies, train providers, and ensure access to morphine. By 2021, Kenya and Rwanda had made significant progress scaling up palliative care services as part of the public health care system, and Uganda's government had instructed public hospitals to start providing these services. In South Africa and Tanzania, governments had yet to commit to publicly funded palliative care services.The experiences in these countries suggest that mixing advocacy, communications, and technical assistance can lead to substantial progress for patient access although full inclusion in universal health coverage remained uncertain in all but Rwanda.

Published
2022
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44. Enhanced postoperative surveillance versus standard of care to reduce mortality among adult surgical patients in Africa (ASOS-2): a cluster-randomised controlled trial

Author

Bruce M Biccard, Leon du Toit, Maia Lesosky, Tim Stephens, Landon Myer, Agya BA Prempeh, Nicola Vickery, Hyla-Louise Kluyts, Alexandra Torborg, Akinyinka Omigbodun, Adesoji Ademuyiwa, Muhammed Elhadi, Mohamed Elfagieh, Bernard Mbwele, Mpoki Ulisubisya, Lazaro Mboma, Daniel Z Ashebir, Mahlet Tesfaye Bahta, Mohammed Hassen, Mikiyas Teferi, Yakob Seman, Eugene Zoumenou, Adam Hewitt-Smith, Janat Tumukunde, Dolly Munlemvo, Atilio Morais, Apollo Basenero, Pisirai Ndarukwa, Nazinigouba Ouerdraogo, Maman Sani Chaibou, Mohyeddine Zarouf, Ahmed Rhassane El Adib, Veekash Gobin, Zimogo Sanogo, Youssouf Coulibaly, Zipporah Ngumi, Tarig Fadalla, Cynthia Iradukunda, Vénérand Barendegere, Isaac O Smalle, Mustapha Bittaye, Ahmadou Lamin Samateh, Mahmoud Elfiky, Maher Fawzy, Wakisa Mulwafu, Vanessa Msosa, Lygia Lopes, Akwasi Antwi-Kusi, Hamza D Sama, Patrice Forget, Dawid van Straaten, Rupert M Pearse, Marichen Puchert, Lucy Rolt, Kris Schwebler, Freddy Kabambi, Tebogo Mabotja, Leandys Cobas, Albino Freitas, Maria Antunes, Bartolomeu Cabo, Domingos Paulo, Carlos Camongua, Yvette Avognon, Osseni Marcos, Raymond Kintomonho, Onesime Demahou, Gisèle Hounsa, Hugues Chobli, Elie Fassinou, Aurore Zoglobossou, Blaise Tchaou, Charles Tchegnonsi, Fifame Amadji, Francine Bossa, Ernest Ahounou, Djima Alao, Roushdane Odérémi, Afissatou Montairou, Oswald Gbehade, Romaric Tobome, Adam Boukari, Patrick Bakantieba, Arouna Sambo, Fanou Lionelle, Nounagnon Gilbert, Julien Attinon, Roger Klikpezo, Aumar Dadjo, Dénis Fanou, Gilberte Hounkpe, Bachabi Fafana, Néné Nguilu, Bodourin Dossou-Yovo, Chantal Segla, Mohamed Toko, Evelyne Gnele-Dedewanou, Michel Noukounwoui, Ethienne Yado, Timothé Gouroubéra, Valéry Adjignon, Serge Mewanou, Aïcha Tchomgang, Urielle Agossou, Fernand Soton, Charbel Azanlin, Lidwine Zomahoun, Rawéléguinbasba Armel Flavien Kabore, Salam Savadogo, Fatou Fleur Rosine Sanou, Farid Belém, Victoria Hien, Cheik Tidiane Hafid W Bougouma, Sie Ahmed Ouattara, Mariam Bambara Kabore, Ouedraogo Nazinigouba, Papougnezambo Bonkoungou, Martin Lankoandé, Mireille Traoré, Patrick Sawadogo, Inès Wenmenga, Boureima Kinda, André Simporé, Christian Sapo, Salah Idriss Traore, Haoua Dipama, Lydie WR Kaboré, Salifou Napon, Télesphore G Kaboré, Arouna Louré, Pélagie PP Tondé, Christian Zoundi, Harouna Sanou, Remy Ndikumana, Carlos Nsengiyumva, Gregory Sund, Alliance Niyukuri, Axel Kwizera, Jean-Claude Niyondiko, Adolphe Manzanza Kilembe, Jean Pierre Mwema Ilunga, Nehema Hailemariam Sarah, Gabriel Mubobo Makeya, Idesbald Mwebe Mwepu, Ted Botawaosenge Likongo, Richard Kapela Mvwala, Raphael Nzau Kapend Mubunda, Noellie Kanka Mukuna, Julie Djondo Pembe, Nicolas Lumuanga Ndaye, Eric Bibonge Amisi, Mike Ilunga Madika, Joe Kembo Lungela, Didier Ndonda Mayemba, Philomene Mamba Diyoyo, Alex Mbo Ngalala, Martin Mamba Mukenga, Patricia Tito Kabuni, Dany Bolimo Mpoto, Herve Inesnku Mole, Louise Keby, Oria Andavo Buti, Anselme Phaka, Belinda Mayenge, Jean Jeacques Kabuley Kalongo, Timothe Kemfuni Mawisa, Rodrigue Tondo Ngwizani, Kuyala Leya, Dieudonne Kisile Sanduku, Timothe Nkemfuni Mawisa, Coco Nseke Mfumu, Mbuta Bolenge, Desire Kinzenzengu Kabuce, Patrick Kintieti, Amelia Mbuluku, Vicky Mahuwa, Tharcice Khonde Mabiala, Guilain Ngoy, Patrick Boloko, Nono Mazangama Mvwama, Jose Kengbanda, Pitchou Mushimbonga, Blaise Kuhapala, Nzosani Marcel, Kienze Guylain, Gerard Mboma, Sandra Zalambo Sagboze, Michel Muteya Manika, Jean Pierre Mumbere Kigayi, Roger Mukanire Cishugi, Placide Buhendwa Mugisho, Roger Baguma, Moïse Kongolo, Michel Mandungu Mbayabu, Crispin Mukendi Muamba, Edmond Banema Kapinga, Vasco Ngolela Kapinga, Guylain Tshimanga Nsumpi, Patrick Kanda Odia, Salomon Bingidimi, Gilbert Kpengbemale, Desire Hubert Bofunga Bosonga Imposo, Patricia Matondo, Servet Lelo, Jeremie Kalambayi, Mohamed Abdel-Ghaffar, Abdelrahman Soliman, Mostafa Abdelrahman, Sameh Shehata, Alia Rabee, Mohamed Abou Heba, Mohamed Rabei Abdelfattah, Tamer Ahmed Maher Ghoniem, Sherif M.K. Shehata, Mohamed Lotfy, Ahmed ElHaddad, Bereket Gebremeskel, Girmay Fisseha, Mebrahtu Abay, Degena Bahrey, Assefa Hika, Abdurezak Ali, Kindie Moges, Jemal Ahmed, Desalegn Abdisa, Abebe Megersa, Wendwosen Abayne, Haftom Berhane, Reiye Esayas, Fitsum Kifle, Kokeb Desita, Abebe Addise, Dagim Shimelash, Shitalem Tadesse, Bezaye Zemedkun, Peniel Kenna, Ayenew Yirdie, Abinet Sisay, Tebikew Gashu, Fassil Mihretu, Yesuf Ahmed, Bekele Debebe, Abdureuf Misgea, Amare Agmas, Rahel Assefa, Abdurahman Gelmo, Seifu Alemu, Brook Damtachew, Merid Mersha, Yaekob Chemere, Samuel Fekadu, Sintayehu Regasa, Bonsa Sileshi, Desalegn Wosen, Rebira Adamu, Gersam Mulugeta, Teshome Bacha, Zewude Gudisa, Kebebe Bekele, Alelign Tasew, Habtamu Gezahegn, Daniel Atlaw, Damtew Solomon, Habtemariam Gebresillasie, Girmaye Tesfaye, Negussie Sarbecha, Biniyam Sahiledengle, Kenbon Seyoum, Gemechu Ganfure, Yohannes Tekalegn, Gosa Tesfaye, Temesgen Ayichew, Shibiru Sendaba, Musefa Redwan, Eyasu Muse, Girma Nina, Bizuneh Sime, Addisalem Tadege, Anbesse Jima, Nugusu Ayalew, Dagmawi Workneh, Daniel Teferi, Momodou T Nyassi, Landing N Sanyang, Omar Jallow, Abdoulie Keita, Kitabu Jammeh, Charles Roberts, Patrick Idoko, Kebba Marenah, Masirending Njie, Musa Marena, Karamba Suwareh, Simon Boissey, Fatoumatta Jarjusey, Awa Jah, Awa Sanyang, Dado Jabbi, Kajali Camara, Armando Correa, John Jabang, Lamin Jaiteh, Lamin Dampha, Aminata Manneh, Baboucarr Sowe, Abdoulie Bah, Edrisa Jawo, Victoria Okoje, Momodou Baro, Yaya Bah, Mustapha Njie, Sainabou Mbowe, Ebrima Kanteh, Sarjo Ceesay, Alagie Manneh, Evans Atito-Narh, Adwoa Wilson, Romeo Hussey, Emmanuel Okine, Jemima Kwarteng, Ridge Ntiamoah, Samuel Dadzie, Mark Aseti, Naa Sowah, Akosua Appiah, Charles Bankah, Patrick Mburugu, Thomas Chokwe, Patrick Olang, Vernon Gacii, Susane Nabulindo, Antony Gatheru, Timothy Mwiti, Caroline Mwangi, Julius Muriithi, Daniel Ojuka, Omondi Ogutu, Evans Masitara, Mohamed Chaudhry, Reuben Kamundi, Annmarie Kangangi, Thomas Massaquoi, Stephen Takow, Felister Moraa, Aziz Munubi, Moses Kimani, Adili Wobenjo, Linda Nguu, Vincent Omeddo, Rose Malaba, Ambrose Nabwana, Anita Mwancha, Alexandria Mugaa, John Wamwaki, Joyce Chege, Seymour Sinari, Andrew Ndonga, Rose Shitsinzi, Walter Akello, Winfred Kimani, Elisha Kirwa, Seno Saruni, Andrew Wainaina, Ernest Nshom, Aidah Kenseko, Kizito Shisanya, Purity Wanjiru, Julliah Cherotich, Judy Kimutai, Benson Wahome, Grace Wangui, Dennis Wamalwa, Stephen Mwangi, John Chege, Tabitha Wanjiku, Carolyne Njoki, Wachira Waititu, Conrad Ambani, Samuel Murimi, Sharon Waithira, Nilson Mouti, Collins Kibet, John Kibet, Virginia Sokobe, Beatrice Jeymah, Antony Kamadi, Faith Gichuri, Steve Moses, David Wasike, Favours Adeya, Caesar Bitta, Stephen Ogendo, Killian Kariuki, Hdaya BenAbdalla, Taha Suliaman, Fatima Ali Abokhzam, Mohaned Isa, Mohammed Huwaysh, Asma Bourawi, Kais Alzubaidy, Mohammed Albaraesi, Sumayyah Bahroun, Abdulmueti Alhadi, Ahmed Msherghi, Amira Mohamed, Ala Khaled, Nouran Aljadi, Elham Bareig, Khaled Elgazwi, Adel Elgazwi, Ibrahim El-busife, Safa Owhida, Almahdi Eltwati, Samah Elakeili, Taha Abubaker, Fatima Elkhfeefi, Soha Younis Hasan, Amal Alttaira, Imbarkah Elmraied, Rim Wishah, Omar Abugassa, Hazem Ahmed, Amera Ellafi, Shoukrie Shoukrie, Nawal Aldokali, Aws ElGammudi, Akram Alkaseek, Hoda Elhaddad, Ayyah Alqaarh, Ahlam Brish, Malek Abudsnnuga, Salsabil Albuaishi, Mohammed Albashri, Marwa Morgom, Mohammed Alawami, Eman Shawesh, Abdullah Almabrouk, Moaz Alwarfalli, Nagia Abeid, Anis Buzreg, Ans Malek, Ameerah Abayu, Butaina Abdulhafith, Wedad Abouruwes, Marim Albakuri, Sabria Almuammari, Esam Alsaghair, Fatheia Alreshi, Hassan Badi, Rabiee Alfetoey, Naji Zubia, Bushray Almiqlash, Abdulsalam Alshuhoumi, Rayet Al-islam Ben Jouira, Amaal Dier, Essra Gebril, Mohammed Abdelkabir, Sana Moussa, Marwa Alfitori, Mabroukah Azbeda, Hajar Alamin, Ejmeya Barka, Omlsaad Mosbah, Rema Abdasalam, Miftah Hiyoum, Maryam Abd allateef, Ibrahim Altomi, Mahdi Alsakloul, Ekhlas Karami, Munyah Alriqeeq, Mabruka Omar, Ashraf Samer, Aml Aemeesh, Ahmad Bouhuwaish, Ahmed Elusta, Sultan Ahmeed, Wesal AlFighi Hassan, Mouadah Ali Altayr, Mohamed Addalla, Abrar Geddeda, Kheria Khoja, Doaa Alhaj, Muaad Etturki, Ahmed Elhadi, Ibrahim Ellojli, Anshirah Shuwayyah, Ahmed Elfaghih, Malak Alduwayb, Mohamed Aleiyan, Wedad Aboubreeq, Soliman Alkassem, Sami Ashour, Hayat Ben Hasan, Najat Ben Hasan, Ali Yahya, Palesa Chisala, Edward Kommwa, Lusayo Simwinga, Agness Chalira, Precious Kachitsa, Onias Mtalimanja, Drissa Traoré, Moussa Sissoko, Moussa Camara, Adama Koita, Sekou Koumaré, Omar Sacko, Mahamadou Coulibaly, Lamine Soumaré, Soumaïla Keita, Sidiki Keita, Hamadoun Dicko, Boubacar Diallo, Boureima Bengaly, Mohamed Keita, Siaka Diallo, Drissa Ouattara, Nouhoun Ongoiba, Seydina Beye, Honoré Berthe, Mamadou Diakite, Mamadou Sima, Adégné Togo, Bakary Dembele, Djibo Diango, Moussa Samake, Youssouf Traoré, Louis Traoré, Ongoïba Oumar, Sogoba Gaoussou, Issaga Traoré, Sidy 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Soummani, Abou Elhassan Taoufik, Meryem Essafti, Aminata Oumou Traoré, Hamzaoui Hamza, Adnane Berdai, El allani Linda, Salhi Oussama, Nelson Mucopo, Machado Banze, Mouzinho Saide, Tomas Sitoi, Artur Machava, Antonio Carlos, Amilton Guidione, Antonio Saide de Carvalho, Natacha Gemo, Samiro Sema Camal, Arsénio Cuna, Ornelos Madeira, Ladino Assuade, Dercio Amde Fernandes, Dulce Alexandre Machavae Fernandes, Mandua Sebastião, Bernard Sikombe, Matti Kandjimi, Ayoub Shekimweri, Diana Shilomboleni, Mbaundju Kandjii, Leonard Kabongo, Cholastic Hangero, Ike Ndjoze, Ruben Nailonga, Immanuel Uukonga, Uutoni Nakanyala, Lavinia Johannes, Adrian Haruzuvi, Chris Terblanche, Natangwe Shimenda, Delwina Katjipu, Hilma Shalimba, Juliah Kaweendwa, Ali Mbuyi, John Oyedele, Mapumba Mulolo, Peter Njuki, Mutombo Ndaie, Akutu Munyika, Hilma Katangolo, David Tjiyokola, Tawanda Mhene, Archbald Masiambiri, Paidamoyo Mandudzo, Sandra Kapepiso, Haziel Mavesere, Cedia Tjihoto, Daylight Manyere, Charlotte Kauraisa, 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Zulaihatu Sarkin-Pawa, Tunde Sholadoye, Benjamin Fomete, Hamisu Yakubu, Abdulkadir Kabiru, Samaila Timothy, Ali Yusuf, Tasiu Saadu, Babangida Mohammed, Abdulghaffar Yunus, Ganiyat Olagunju, Muhammad Aminu, Mohammad Idris, Musliu Tolani, Nasiru Dalhat, Samuel Gana, Talent Adike, Lofty-John Anyanwu, Abdurrahman Sheshe, Sani Aji, Mamuda Atiku, Raphael Attah, Abubakar Muhammed, Rasaki Oseni, Halima Salisu-Kabara, Benjamin Nkemjika, Omotayo Salami, Adekunle Akadri, Bukola Olayinka, Clement Onuoha, Umar Usman Jamaare, Auwalu Saminu Jibrin, Sani Giade Abdullahi, Ibrahim Ishaku, Adenike Odewabi, John Bamigboye, Oladapo Kuforiji, Chidiebere Ogo, Stella Ogunmuyiwa, Abdussemee Abdurrazzaaq, Adebayo Tanimola, Michael Adeyanju, Oluwatimilehin Andero, Temitope Ojo, Olusi Adedotun, Gbadamosi Kehinde, Jimoh Buraimoh, Kabiru Muhammad, Sophia Baidoo, Patrick Okoli, Azeez Adigun, Ekene Ezeonye, Kabir Isa, Yetunde Aremu-Kasumu, Kamil Shoretire, Peter Enesi, Amechi Ezike, Olatunde Olawoye, Emmanuel Ugwu, Christopher Ukah, Abolade Olugbenga, Nwachukwu Chidiebere, Nasiru Abdulraman, Adebiyi Olusegun, Alisa Halisa, Semiat Yusuf, Jamila Salisu, Chidiebube Okoro, Abdul Suleiman, Fabian Onowighose, Aliyu Farinyaro, Suleiman Baba, Umar Abdulmajid, Aisha Abdurrahman, Ogochukwu Obi, Olatunde Alabi, William Adeyemi, Jelili Salau, Jones Taiwo, Nnaemeka Nwafulume, Taiye Ibiyeye, Edith Agu, Ayodeji Danboy, James Abdulazeez, Christopher Ekwunife, Chimaobi Nnaji, Chigozirim Onyekpere, Amara Arunsi, Jude Egwim, Obianuju Nwana, Nnabuike Ojiegbe, Charles Mbamba, Paul Ngwu, Frank Imahigbe, Emmanuel Okoroji, Iloh Ikenna, Abdulrahman Mohammed, Adebayo Adeniyi, Toluwalope Ariyo, Olajide Gabriel, Tesleem Orewole, Salawu Idris, Idowu Adebara, Abiodun Okunlola, Akinwale Akinbade, Oluwasesan Afolabi, Adewumi Bakare, Olabisi Adeyemo, Benjamin Ugwu, Samuel Nuhu, Henry Embu, Erdoo Isamade, Chinedu Obikili, Amaka Ocheke, Solomon Peter, Donald Orshio, Peter Onuminya, Jack Okopi, Olufemi Bankole, Bosede Afolabi, Dapo 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Onajin-Obembe, Bright Obasuyi, Richard Echem, Ihuoma Mike-Elechi, Job Otokwala, Mark Edubio, Catherine Eyo, Isaac Udo, Aliyu Abdulrahman, A.A. Abdullahi, Ibrahim Galadima Bello, Usman Adinoyin Mohammed, Abidemi Oyaromade, Mohammed Bello, Usman Muhammad, Emeri Mbah, Hyacinth Okereke, Almustapha Aminu, Anthony Ahmadu, Abu Rogers, Peter Samai, Sao Amara, Margaret Yankuba, Mary Josayah, Jayah Swarray Jnr, Alusine Dawo, Peter George, Mustapha Kabba, Mohamed Bah, Charles Mondeh, Ibrahim Kapuwa, Mohamed Sheku, Philip Mattia, Brima Sesay, Jones O.A. Omoshoro-Jones, Motselisi Mbeki, Estie Cloete, Philip Anderson, Busi Mrara, Annemarie Steyn, Tsakani Mhlari, Nic Proctor, Caroline Robertson, Gillian Lamacroft, Usha Singh, Sebenzile Sikhakhane, Kelly Gate, Shepherd Nzenza, John Tshimbalanga Kasonga, Sibongile Ndebele, Patrick Lufuta Kande, Jody Davids, Tino-vito Orlandi, Marischka de Jong, Hugo Stark, Francois Roodt, Jonathan Hall, Ian Nortje, Akanimo Akpakan, Vishendran Govindasamy, Ronisha Sathiram, Mohammad Kathrada, Zane Farina, Lucio Frittella, Charles Kohler, Sibuyiselwe Lubelwana, Sarwat Ikram-Hameed, Adriaan Smit, Muneerah Cassiem, Yvonne Freeman, Saaliha Goga, Larissa Cronje, Constantin Buzdugan, Subash Chirkut, Priyadeshni Singh, Sandhya Jithoo, Vivesh Rughubar, John Arnold, Rishan Bipath, Suman Mewa Kinoo, Ncumisa Khanyisa Msolo, Fleur Ackermans-Deijnen, Tshegofatso Mmasello Emma Boka, Martyn Biccard Greenwood, Shakthi Anand Jayrajh, Devarani Naidoo, Syndrini Reddy, Devandiran Harriraman Rungan, Kylene Subrayen, John Roos, Nina Tredoux, Pascal Plumacher, Anthony Reed, Harald Steinhaus, Mariesa Nock, Paul Ryan Herselman, Gareth Davies, Talitha Harvey, Franklin Muller, Willem Naude, Tania Pretorius, Johan Jochemus Swart, Merryn Walls, Prashant Gokal, Nicolette Rorke, Farzaana Dhoodhat, Precious Dzanibe, Mohammed Yusuf Hussain, Ashmita Junpath, Ameela Maharaj, Hylda Makanisi, Khalid Moosa, Ting Ting Wong, Sean Mould, Trisha Ramsamy, Roel Matos-Puig, Hayley Morgan, Nadeem Nabeebuccas, Ria Devi Naidoo, Viantha Pather, Vasheel Vasheel Bahadur, Renilda Pillay, Zahnne Fullerton, Nicole Bell, Bongisa Grey, Vincent Lorenzo Visentin, Hendrik Adriaan Van Zyl, Terri Anne Killingbeck, Emile Maneveldt, Gerhard Thiart, Magdelena May Venter, Oostewalt Swart, Mariette Grobelaar, Carel Cairns, David Bishop, Christien Steenkamp, Thandekile Khumalo, Noel Naidoo, Ross Murray, Martin Kopieniak, Melusi Sishange, Mxolisi Brian Ndimande, Megan Jaworska, Sarwat Ikram, Bence Rainier, Renier J Liebenberg, Helena D Zwiegers, Philip M Nortje, Kamal Bhagwan, Margot Flint, Robert Dyer, Simone Adams, Yoshua Bwambale, Danny Ngomo, Patrice Kanku, Nivashen Pillay, Alexa de Castro, Atisha Maharaj, Janine Carim, Jenna Leigh Taylor, Karl M Köhne, Leanne W Drummond, Leanne Temlett, Lieze Geldenhuys, Yvonne Seilbea, Kathryn Naidoo, Nicola A Kalafatis, Stefné Verwey, Thulile Biyase, Theroshnie Kisten, Belinda S Kusel, Timothy Craig Hardcastle, Richard Magagula, Christian Kampik, Kuzolunga Xulu, Sivuyisiwe Solala, Mia Sayed, Basil Enicker, Anil Madaree, Innocent Mukama, Gladmore Madombwe, Nonhlanhla Zulu, Nompumelelo Gasa, Nokuzula Kanjana, Sebenzile Buthelezi, Thembelihle Buthelezi, Andries Brink, Francois Potgieter, Busisiwe Mrara, Zaynab Alexander, Charles Choto, Paula Ima, Zintle Gxagxisa, Baphethuxolo Ningiza, Gillian Lamacraft, Jerome Mogorosi, Nadia du Plessis, Leonie de Man, Suné Thompson, Gerrit van Heerden, Edwin W Turton, Pieter M van der Linde, Josephine K Teme-Pitse, Reitumetse Tladi, Gillian D Saffy, Ene-Mari Roscher, Kristel Fortune, George Barnard, Tiisetso Makhasane, Evan Bowen, Akangcha Pal, Rachel Moore, Maria Fourtounas, Mary Augusta Adam, Renessa Arumugan, Gabriella Hyman, Jaclyn Jonosky, Maninginingi Makondo, Heveshan Moodley, Phillip Munda, Mzwandile Nyalungu, Victor Olusola, Sohan Zane Pinto, Tristan Pillay, Lucinda Singh, Paul Mwindekuma Wondoh, John Devar, Boitumelo Baloyi-Mnisi, Zach Koto, Matlou Ernest Mabitsela, Sibongile Ruth Ndlovu, Branny Mthelebofu, Colin Beck, Matthew Dold, Alice Fan, Shannon MacQueen, Thembani Matabata, Catherine Mpehle, Charné Kulenkampf, Tsakani McCreath Mhlari, Simangele Cecilia Nyoka-Mokgalong, Felix Thumba Masinge, Randhir Ramnath Gunpath, Maropeng Petrus Pat Mothwa, Jo-Anne Asenath Mothwa, Danai Mhlanga, Jamie-Lyn Colly, Aunel Mallier Peter, Khalid Ben Hameda, Pulane Mokae, Stella Josephine Moumakoe, Kelechi Ekeh, Nezingu Lengo, Marnus Booyens, Inge Louise Seale, Pieter Daniel Theron, Nicolaas Abraham Schuman, Amber Carlyn Sonn, Jacobus Lukas Stander, Nadia Cloete, Marius Cloete, Catherine Ann Makepeace, Ronel van der Westhuizen, Leanne Robyn Messiahs, Amy Ruth Visagie, Fatima Vawda, Frans Christiaan Voster, Deepika Dhilraj, Oliver Smith, Stefan Bolon, Daniel Montwedi, Motsilisi Mbeki, Jayde Wyngaard, Mthunzi Ngcelwane, Thomas Kleyenstuber, Phyllis Phukubye, Liesel Schärf, Grace Laker, Elizabeth Semenya, Reinhard Dembskey, Thomas Tarlton, Tapiwa Jiri, Ngoie Hubert Mushid, Nhlanhla Samuel Ngwenya, Hazel Morongoa Mogodi, Carmen Sinevici, Anthony Osarogie Usenbo, Naledi Fodo, Anesu Chimini, Ntetelelo Sikobi, Sinovuyo Nokwange, Mluleki Noqhamza, Qumba Thembisa, Kajake Anantha Padmanabha Bhat, Rabin Mathew, Katrin Middleton, Abdus-sami Adewunmi, Craig Dickson, Humairah Bulbulia, Bianka Bester, Michelle de Klerk, Christia Benade, Francois Viljoen, Monique Fischer, Khalid Alfaki, Abdalmalik Awad, Abdelsalam Algray, Mohammed Elsiddig, Suha Mohamed, Salih Mahmoud, Muhammed Osman, Asia Elgailany, Mazin Suliman, Hanaa Mohammed, Lina Aljeally, Mohammed Dirar, Mohammed Osman, Mazin Mohamed, Mohamed Elhasan, Abrar Widatalla, Abubakr Abubakr, Eman Mohamed, Alshareef Nour, Ntonto Doris Gama, Dolorosa Khetsiwe Shabangu, Cynthia Iradikunda, Samuel Mkoko, Paul Kisanga, Emmanuel Lema, Benson Lyimo, Mohamed Binde, Alphonce Chandika, Salim Salim, Sylvia Jumbe, Abel Makubi, Vihar Kotecha, Felician Kachinde, Museleta Nyakiroto, Emmanuel Jitambi, Venant Geofrey, Johaphes Josiah, Phinius Makubi, Frank Manumbu, Suzan Mlingwa, Ernest Ibenzi, Peter Mbelle, Kato Peleus, Enid Chiwanga, Nillah Richard, Shoo Leonard, Paulo Sanka, Subira Mushi, Bashir Nyangasa, Mohamed Janabi, Naizihijwa Majani, Pedro Palangyo, Evarist Nyawawa, William Ramadhan, Faraj Lydenge, Gileard Gabriel Masenga, Sakina Rashid, Mubashir Jusabani, Ansbert Ndebea, Jenitha Cheru, Margaret Henjewele, Greyson Kilimanjaro, Sarah Sikimata, Deocles Donatus, Hazina Maduhu, Tumaini Mariro, Given Massasi, Moshi Moshi Shabani, Braison Cholela, Marco Mgeleka, Yohatinus Mbilinyi, Faraja Chiwanga, Bilton Exavery, Caspar Haule, Samson Ndile, Sirili Harya, Julieth Magandi, Deogratius Manyama, Redempta Matindi, Adam Moshi, Daudi Kitwana, Merida Makia, Philip Muhochi, Miriam Herman, Clauda Miombo, Furaha Kahindo, Langtone Kishebuka, Elijah Ussiri, Gloria Kinasa, Patrick Adel, Eric Malaba, Vensesla Sakwari, Sadot Lugereka, Mohamed Mungia, George Mocha, Herman Wella, Cecilia Protas, Patrick Karua, Ahmada Kashagama, Faraja Mwasambugu, Suzana Kajeri, Jacquiline Mchilla, Elibariki Lucumay, Robert Maise, Amon Marti, Beatrice Mahundi, Frederika Jager, Charles Majani, Ludovick Rukeha, Tareeq Mohamed, Nabila Fuad, Winifrida Halinga, Elias Chrisant, Gilbert Msoma, Titus Kihwili, Gadiel Temu, Naima Yusuf, Rashid Saleh, Rashid Inoja, Eva Shang'a, Stella Ibrahim, Hussein Msuma, Edwin Edward, Paul Kilamile, Stephen Mwakyolile, Talkana Adja, Edem Gueouguede, Hafoudhoi Oussene Seddoh, Saliou Adam, Pilakimwe Egbohou, Mawunyo Ahomagnon, Olivier Kadjossou, Abdul-Bassiti Boukari, Mary T Nabukenya, Ruth Muhindo, Peter Waswa, Peter Kaahwa Agaba, Daphne Kabatoro, Joseph Kayong, Margaret Naggujja, Nabasiige Rehema, Phiona Nansubuga, Daniel Kavuma, Aggrey Lubikire, Hope Bisilikirwa, Godfrey Ssebaggala, Emmanuel Muwema, Humble Joan Agaba, John Kiconco, Nicholas Wataaka, Bonet Chan, Mary Juliet Nampawu, Fred Bulamba, Emmanuel Bua, Christine Mugala, Caroline Nyakato, John Paul Ochieng, Linda Kyomuhendo Jovia, George Kateregga, Rachel Alum, Lazia Najjuma, Gorret Nampiina, Andrew Kintu, Joshua Sempiira, Luzige Simon, Peter Kayima, Jacob Eyul, Erick Odwar, Rita Nkwine, Christine Namata, Elizabeth Nabakka, Denis Kakaire, Velda Mushangwe-Mtisi, Erisha Munhamo, Celestino Dhege, Juliet Hungwa, Hemish Jasi, Crispin Ntoto, Derek Matsika, Brightson Mutseyekwa, Joseph Zimbovoora, Beaulah Gudyanga, Dennis Mazingi, Chenesa Mbanje, Busisiwe Mlambo, Michael Chiwanga, Harunavamwe N Chifamba, Sarudzai Zhou, Esta Hove, Shamiso Dende, Beauty Manjengwa, Penias Kapisa, null Mashava, Caritas Chiura, Locadia Katsukunya, Godfrey Muguti, Doreen Mashava, Elton Ndhlovu, Zanele Mangwangwa, and Nombulelo Dube

Subjects
Adult, medicine.medical_specialty, Standard of care, business.industry, Psychological intervention, MEDLINE, Standard of Care, General Medicine, Articles, Hospitals, Hospitalization, Intervention (counseling), Relative risk, Emergency medicine, Africa, medicine, Humans, In patient, Female, Cluster randomised controlled trial, Postoperative Period, business, Surgical patients
Abstract

Summary Background Risk of mortality following surgery in patients across Africa is twice as high as the global average. Most of these deaths occur on hospital wards after the surgery itself. We aimed to assess whether enhanced postoperative surveillance of adult surgical patients at high risk of postoperative morbidity or mortality in Africa could reduce 30-day in-hospital mortality. Methods We did a two-arm, open-label, cluster-randomised trial of hospitals (clusters) across Africa. Hospitals were eligible if they provided surgery with an overnight postoperative admission. Hospitals were randomly assigned through minimisation in recruitment blocks (1:1) to provide patients with either a package of enhanced postoperative surveillance interventions (admitting the patient to higher care ward, increasing the frequency of postoperative nursing observations, assigning the patient to a bed in view of the nursing station, allowing family members to stay in the ward, and placing a postoperative surveillance guide at the bedside) for those at high risk (ie, with African Surgical Outcomes Study Surgical Risk Calculator scores ≥10) and usual care for those at low risk (intervention group), or for all patients to receive usual postoperative care (control group). Health-care providers and participants were not masked, but data assessors were. The primary outcome was 30-day in-hospital mortality of patients at low and high risk, measured at the participant level. All analyses were done as allocated (by cluster) in all patients with available data. This trial is registered with ClinicalTrials.gov , NCT03853824 . Findings Between May 3, 2019, and July 27, 2020, 594 eligible hospitals indicated a desire to participate across 33 African countries; 332 (56%) were able to recruit participants and were included in analyses. We allocated 160 hospitals (13 275 patients) to provide enhanced postoperative surveillance and 172 hospitals (15 617 patients) to provide standard care. The mean age of participants was 37·1 years (SD 15·5) and 20 039 (69·4%) of 28 892 patients were women. 30-day in-hospital mortality occurred in 169 (1·3%) of 12 970 patients with mortality data in the intervention group and in 193 (1·3%) of 15 242 patients with mortality data in the control group (relative risk 0·96, 95% CI 0·69–1·33; p=0·79). 45 (0·2%) of 22 031 patients at low risk and 309 (5·6%) of 5500 patients at high risk died. No harms associated with either intervention were reported. Interpretation This intervention package did not decrease 30-day in-hospital mortality among surgical patients in Africa at high risk of postoperative morbidity or mortality. Further research is needed to develop interventions that prevent death from surgical complications in resource-limited hospitals across Africa. Funding Bill & Melinda Gates Foundation and the World Federation of Societies of Anaesthesiologists. Translations For the Arabic, French and Portuguese translations of the abstract see Supplementary Materials section.

Published
2021

45. Outcome of liver cancer patients with SARS‐CoV‐2 infection: an international, multicentre, cohort study

Author

Muñoz- Martínez, Sergio, Sapena, Victor, Forner, Alejandro, Bruix, Jordi, Sanduzzi-Zamparelli, Marco, Ríos, José, Bouattour, Mohamed, El Kassas, Mohamed, Guedes Leal, Cassia Regina, Mocan, Tudor, Nault, Jean-Charles, Camargo Pinheiro Alves, Rogerio, Reeves, Helen L., da Fonseca, Leonardo, García-Juárez, Ignacio, Pinato, David J., Varela, María, Alqahtani, Saleh A., Alvares-da-Silva, Mario Reis, Bandi, Juan C., Rimassa, Lorenza, Lozano, Mar, González Santiago, Jesús M., Tacke, Frank, Sala, Margarita, Anders, Maria Margarita, Lachenmayer, Anja, Piñero, Federico, França, Alex, Guarino, María, Elvevi, Alessandra, Cabibbo, Giuseppe, Peck-Radosavljevic, Markus, Rojas, Ángela, Vergara, Mercedes, Braconi, Chiara, Pascual, Sonia, Perelló, Christie, Mello, Vivianne, Rodríguez-Lope, Carlos, Acevedo, Juan, Villani, Rosanna, Hollande, Clemence, Vilgrain, Valérie, Tawheed, Ahmed, Ferguson Theodoro, Carmem, Sparchez, Zeno, Blaise, Lorraine, Viera-Alves, Daniele E., Watson, Robyn, Carrilho, Flair J., Moctezuma-Velázquez, Carlos, D'Alessio, Antonio, Iavarone, Massimo, Reig, María, Ministerio de Sanidad (España), European Association for the Study of the Liver, Cancer Treatment and Research Trust, Wellcome Trust, Cancer Research UK, Instituto de Salud Carlos III, Bristol Myers Squibb Foundation, Muñoz- Martínez, Sergio [0000-0003-0663-0575], Sapena, Victor [0000-0003-4379-6486], Forner, Alejandro [0000-0002-9014-4950], Ríos, José [0000-0002-0716-8784], González Santiago, Jesús M. [0000-0003-4667-4492], Rojas, Ángela [0000-0003-0853-4800], Hollande, Clemence [0000-0002-2287-0635], Muñoz- Martínez, Sergio, Sapena, Victor, Forner, Alejandro, Ríos, José, González Santiago, Jesús M., Rojas, Ángela, Hollande, Clemence, and Sergio Muñoz-Martínez, Victor Sapena, Alejandro Forner, Jordi Bruix, Marco Sanduzzi-Zamparelli, José Ríos, Mohamed Bouattour, Mohamed El-Kassas, Cassia R. G. Leal, Tudor Mocan, Jean-Charles Nault, Rogerio C. P. Alves, Helen L. Reeves, Leonardo da Fonseca, Ignacio García-Juárez, David J. Pinato, María Varela, Saleh A. Alqahtani, Mario R. Alvares-da-Silva, Juan C. Bandi, Lorenza Rimassa, Mar Lozano, Jesús M. González Santiago, Frank Tacke, Margarita Sala, María Anders, Anja Lachenmayer, Federico Piñero, Alex França, Maria Guarino, Alessandra Elvevi, Giuseppe Cabibbo, Markus Peck-Radosavljevic, Ángela Rojas, Mercedes Vergara, Chiara Braconi, Sonia Pascual, Christie Perelló, Vivianne Mello, Carlos Rodríguez-Lope, Juan Acevedo, Rosanna Villani, Clemence Hollande, Valérie Vilgrain, Ahmed Tawheed, Carmem Ferguson Theodoro, Zeno Sparchez, Lorraine Blaise, Daniele E. Viera-Alves, Robyn Watson, Flair J. Carrilho, Carlos Moctezuma-Velázquez, Antonio D'Alessio, Massimo Iavarone, Maria Reig

Subjects
Settore MED/12 - Gastroenterologia, Carcinoma, Hepatocellular, Hepatology, Hepatocellular carcinoma, SARS-CoV-2, Liver Neoplasms, COVID-19, hepatocellular carcinoma, mortality, Cohort Studies, liver cancer, COVID-19 Testing, Cross-Sectional Studies, Humans, Mortality, Liver cancer, Retrospective Studies
Abstract

Background & Aims Information about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with liver cancer is lacking. This study characterizes the outcomes and mortality risk in this population. Methods Multicentre retrospective, cross-sectional, international study of liver cancer patients with SARS-CoV-2 infection registered between February and December 2020. Clinical data at SARS-CoV-2 diagnosis and outcomes were registered. Results Two hundred fifty patients from 38 centres were included, 218 with hepatocellular carcinoma (HCC) and 32 with intrahepatic cholangiocarcinoma (iCCA). The median age was 66.5 and 64.5 years, and 84.9% and 21.9% had cirrhosis in the HCC and iCCA cohorts respectively. Patients had advanced cancer stage at SARS-CoV-2 diagnosis in 39.0% of the HCC and 71.9% of the iCCA patients. After a median follow-up of 7.20 (IQR: 1.84–11.24) months, 100 (40%) patients have died, 48% of the deaths were SARS-CoV-2-related. Forty (18.4%) HCC patients died within 30-days. The death rate increase was significantly different according to the BCLC stage (6.10% [95% CI 2.24–12.74], 11.76% [95% CI 4.73–22.30], 20.69% [95% CI 11.35–31.96] and 34.52% [95% CI 17.03–52.78] for BCLC 0/A, B, C and D, respectively; p = .0017). The hazard ratio was 1.45 (95% CI 0.49–4.31; p = .5032) in BCLC-B versus 0/A, and 3.13 (95% CI 1.29–7.62; p = .0118) in BCLC-C versus 0/A in the competing risk Cox regression model. Nineteen out of 32 iCCA (59.4%) died, and 12 deaths were related to SARS-CoV-2 infection. Conclusions This is the largest cohort of liver cancer patients infected with SARS-CoV-2. It characterizes the 30-day mortality risk of SARS-CoV-2 infected patients with HCC during this period., Spanish Health Ministry; Ricerca Corrente, Grant/Award Number: RC2019/105-01, RC2018/105-01 and RC2017/105-01; European Association for the Study of the Liver (Andrew Burroughs Fellowship); Cancer Treatment and Research Trust (CTRT); Wellcome Trust Strategic Fund, Grant/Award Number: PS3416; Cancer Research UK (CR UK) centre, Grant/Award Number: C9380/A26813, C18342/A23390 and C9380/A18084; Instituto de Salud Carlos III, Grant/Award Number: PI18/0358, PI15/00145, CD18/00126, PI19/00819, FI19/00222, 16-0026, PI044031, PI18/00768, PI18/00542 and PI13/01229; Bristol Myers Squibb and Celgene; Cancer Research UK, Grant/Award Number: RCCPDB-Nov21/100008

Published
2022

46. The outcome of patients with Hodgkin lymphoma and early relapse after autologous stem cell transplant has improved in recent years

Author

Ali Bazarbachi, Ariane Boumendil, Hervé Finel, Irma Khvedelidze, Joanna Romejko-Jarosinska, Alina Tanase, Saad Akhtar, Tarek Ben Othman, Mohammad Ma’koseh, Boris Afanasyev, Jean Cheikh, Javier Briones, Zafer Gülbas, Rose-Marie Hamladji, Tugrul Elverdi, Didier Blaise, Carmen Martínez, Eleonora Alma, Kazimierz Halaburda, Aida Botelho Sousa, Bertram Glass, Steven Robinson, Silvia Montoto, and Anna Sureda

Subjects
Adult, Brentuximab Vedotin, Cancer Research, Immunoconjugates, Oncology, Hematopoietic Stem Cell Transplantation, Humans, Hematology, Neoplasm Recurrence, Local, Hodgkin Disease, Transplantation, Autologous, Retrospective Studies
Abstract

Hodgkin lymphoma (HL) patients who relapse after autologous-stem-cell- transplantation (auto-SCT) have traditionally had a poor prognosis. We analyzed 1781 adult HL patients who relapsed between 2006 and 2017 after a first auto-SCT. The 4-year overall survival (OS) after relapse continuously increased from 32% for patients relapsing in 2006-2008, to 63% for patients relapsing in 2015-2017 (p = 0.001). The improvement over time was predominantly noted in patients who had an early relapse (within 12 months) after auto-SCT (p = 0.01). On multivariate analysis, patients who relapsed in more recent years and those with a longer interval from transplant to relapse had a better OS, whereas increasing age, poor performance status, bulky disease, extranodal disease and presence of B symptoms at relapse were associated with a worse OS. Brentuximab vedotin (BV), checkpoint inhibitors (CPI) and second transplant (SCT2; 86% allogeneic) were used in 233, 91 and 330 patients respectively. The 4-year OS from BV, CPI, and SCT2 use was 55%, 48% and 55% respectively. In conclusion, the outcome after post-transplant relapse has improved significantly in recent years, particularly in the case of early relapse. These large-scale real-world data can serve as benchmark for future studies in this setting.

Published
2022
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47. Evaluation of patients’ and practitionners’ satisfaction with the use of hypnosis during a thermal endovenous procedure

Author

N, Loseto, N, Zenati, C, Seinturier, and S, Blaise

Subjects
Patient Satisfaction, Humans, Personal Satisfaction, Prospective Studies, Anxiety, Cardiology and Cardiovascular Medicine, Hypnosis
Abstract

In the field of vascular surgery, hypnosis has been used in the creation of venous approaches but also as a complement to local anesthesia during more extensive vascular surgery, including the insertion of abdominal aortic aneurysm stents. The practice of thermal endovenous procedures seems to us to be conducive to hypnotic support in particular to reinforce hypnoanalgesia.We present a prospective and monocentric observational study at the University Hospital of Grenoble with consecutive inclusions whose objective was to evaluate the interest and the satisfaction of the patients and practionners about the practice of hypnosis during procedures of thermal endovenous treatments.Among the 31 patients treated with endovenous laser, 27 accepted the hypnosis proposal, 16 had hypnosis considered as formal and 13 conversational hypnosis and 10 conversation only. Among them, 29% of patients considered that the hypnoanalgesia technique had enormously relaxed them and 19% "very relaxed"; 42% of patients considered themselves "good", 32% "very good" and 19% "extremely good" at the end of the procedure. Concerning the practitioners performing the endovenous procedure, more than half (51, 51%) considered that hypnoanalgesia relaxed the patient "moderately and/or a lot". The results were as a whole point to a high level of satisfaction on the part of patients and practitioners with the practice of procedures with various levels of hypnosis induction. Despite many biases, this study has the merit of concluding that the patients were very satisfied with the apprehension of these gestures as well as the practitioners, and this without any additional time during the procedure.

Published
2022
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48. Pharmacokinetics, Safety, and Efficacy of Gadopiclenol in Pediatric Patients Aged 2 to 17 Years

Author

Elżbieta, Jurkiewicz, Silvia, Tsvetkova, Anna, Grinberg, and Blaise, Pasquiers

Subjects
Adult, Contrast Media, Humans, Gadolinium, Radiology, Nuclear Medicine and imaging, General Medicine, Child, Azabicyclo Compounds, Magnetic Resonance Imaging
Abstract

The aim of this study was to evaluate the pharmacokinetic (PK) profile, safety, and efficacy of gadopiclenol, a new high-relaxivity gadolinium-based contrast agent, in children aged 2 to 17 years.Children scheduled to undergo contrast-enhanced magnetic resonance imaging of the central nervous system (CNS cohort) or other organs (body cohort) were included sequentially into 3 age groups (12-17, 7-11, and 2-6 years). Gadopiclenol was administered at the dose of 0.05 mmol/kg. A sparse sampling approach was applied, with 4 blood samples per child collected up to 8 hours postinjection. Population PK modeling was used for the analysis, including the CNS cohort and adult subjects from a previous study. Adverse events were recorded, and efficacy was assessed for all children.Eighty children were included, 60 in the CNS cohort and 20 in the body cohort. The 2-compartment model with linear elimination from the central compartment developed in adults was also suitable for children. Pharmacokinetic parameters were very similar between adults and children. Terminal elimination half-life was 1.82 hours for adults and 1.77 to 1.29 hours for age groups 12-17 to 2-6 years. The median clearance ranged from 0.08 L/h/kg in adults and 12-17 years to 0.12 L/h/kg in 2-6 years. The median central and peripheral volumes of distribution were 0.11 to 0.12 L/kg and 0.06 L/kg, respectively, for both adults and children. Simulations of plasma concentrations showed minor differences, and median area under the curve was 590 mg·h/L for adults and 582 to 403 mg·h/L for children. Two patients (2.5%) experienced nonserious adverse events considered related to gadopiclenol: a mild QT interval prolongation and a moderate maculopapular rash. Despite the limited number of patients, this study showed that gadopiclenol improved lesion detection, visualization, and diagnostic confidence.The PK profile of gadopiclenol in children aged 2 to 17 years was similar to that observed in adults. Thus, there is no indication for age-based dose adaptation, and comparable plasma gadopiclenol concentrations are predicted to be achieved with body weight-based dosing in this population. Gadopiclenol at 0.05 mmol/kg seems to have a good safety profile in these patients and could improve lesion detection and visualization, therefore providing better diagnostic confidence.The aim of this study was to evaluate the pharmacokinetic (PK) profile, safety, and efficacy of gadopiclenol, a new high-relaxivity gadolinium-based contrast agent, in children aged 2 to 17 years.Children scheduled to undergo contrast-enhanced magnetic resonance imaging of the central nervous system (CNS cohort) or other organs (body cohort) were included sequentially into 3 age groups (12–17, 7–11, and 2–6 years). Gadopiclenol was administered at the dose of 0.05 mmol/kg. A sparse sampling approach was applied, with 4 blood samples per child collected up to 8 hours postinjection. Population PK modeling was used for the analysis, including the CNS cohort and adult subjects from a previous study. Adverse events were recorded, and efficacy was assessed for all children.Eighty children were included, 60 in the CNS cohort and 20 in the body cohort. The 2-compartment model with linear elimination from the central compartment developed in adults was also suitable for children. Pharmacokinetic parameters were very similar between adults and children. Terminal elimination half-life was 1.82 hours for adults and 1.77 to 1.29 hours for age groups 12–17 to 2–6 years. The median clearance ranged from 0.08 L/h/kg in adults and 12–17 years to 0.12 L/h/kg in 2–6 years. The median central and peripheral volumes of distribution were 0.11 to 0.12 L/kg and 0.06 L/kg, respectively, for both adults and children. Simulations of plasma concentrations showed minor differences, and median area under the curve was 590 mg·h/L for adults and 582 to 403 mg·h/L for children. Two patients (2.5%) experienced nonserious adverse events considered related to gadopiclenol: a mild QT interval prolongation and a moderate maculopapular rash. Despite the limited number of patients, this study showed that gadopiclenol improved lesion detection, visualization, and diagnostic confidence.The PK profile of gadopiclenol in children aged 2 to 17 years was similar to that observed in adults. Thus, there is no indication for age-based dose adaptation, and comparable plasma gadopiclenol concentrations are predicted to be achieved with body weight–based dosing in this population. Gadopiclenol at 0.05 mmol/kg seems to have a good safety profile in these patients and could improve lesion detection and visualization, therefore providing better diagnostic confidence.

Published
2022
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49. Measurable residual disease, FLT3‐ITD mutation, and disease status have independent prognostic influence on outcome of allogeneic stem cell transplantation in NPM1‐mutated acute myeloid leukemia

Author

Rama Al Hamed, Myriam Labopin, Etienne Daguindau, Riitta Niittyvuopio, Anne Huynh, Gerard Socié, Micha Srour, Jean Henri Bourhis, Nicolaus Kröger, Eleni Tholouli, Goda Choi, Xavier Poiré, Hans Martin, Marie‐Thérèse Rubio, Pavel Jindra, Didier Blaise, Dietrich Beelen, Hélène Labussière‐Wallet, Arnon Nagler, Ali Bazarbachi, Mohamad Mohty, Albert Einstein College of Medicine [New York], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CEREST-TC [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital JeanMinjoz, Helsinki University Central Hospital [Finland] (HUCH), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Lille, Université de Lille, Institut Gustave Roussy (IGR), Département d'hématologie [Gustave Roussy], University Hospital Hamburg-Eppendorf, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Manchester Royal Infirmary, University of Manchester [Manchester], University of Groningen [Groningen], Cliniques universitaires St Luc [Bruxelles], Goethe-Universität Frankfurt am Main, Service d’Hématologie Adulte [Hôpitaux de Brabois, CHU Nancy], Centre Hospitalier Universitaire de Nancy (CHU Nancy), Medicine Charles University and General Faculty Hospital in Prague, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University Hospital [Essen, Germany], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Chaim Sheba Medical Center, American University of Beirut [Beyrouth] (AUB), Centre International des greffes [CHU Saint-Antoine] (EBMT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Comprehensive Cancer Center [Helsinki, Finland], Helsinki University Hospital [Finland] (HUS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University Medical Center Groningen [Groningen] (UMCG), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Charles University Hospital Pilsen, Dept. of Bone Marrow Transplantation, University Hospital, Essen, Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Gestionnaire, Hal Sorbonne Université, NUNES, Jacques A, HUS Comprehensive Cancer Center, Clinicum, and Department of Oncology

Subjects
Adult, FLT3‐ITD, Cancer Research, FLT3-ITD, 3122 Cancers, Medizin, [SDV.CAN]Life Sciences [q-bio]/Cancer, acute myeloid leukemia, RELAPSE, [SDV.CAN] Life Sciences [q-bio]/Cancer, AML, Recurrence, hemic and lymphatic diseases, VERSUS-HOST-DISEASE, Humans, Radiology, Nuclear Medicine and imaging, NUCLEOPHOSMIN NPM1, RC254-282, Retrospective Studies, ACUTE MYELOGENOUS LEUKEMIA, Hematopoietic Stem Cell Transplantation, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, ADULTS, Prognosis, NPM-1 mutation, NPM‐1 mutation, SORAFENIB, Leukemia, Myeloid, Acute, DEFINITION, Oncology, fms-Like Tyrosine Kinase 3, Mutation, SURVIVAL, minimal residual disease, Nucleophosmin
Abstract

Nucleophosmin-1 (NPM1) mutations in acute myeloid leukemia (AML) confer a survival advantage in the absence of FLT3-internal tandem duplication (FLT3-ITD). Here, we investigated the main predictors of outcome after allogeneic hematopoietic stem cell transplantation (allo-HCT). We identified 1572 adult (age >= 18 year) patients with NPM1-mutated AML in first complete remission (CR1:78%) or second complete remission (CR2:22%) who were transplanted from matched sibling donors (30.8%) or unrelated donors (57.4%) between 2007 and 2019 at EBMT participating centers. Median follow-up for survivors was 23.7 months. FLT3-ITD was present in 69.3% of patients and 39.2% had detectable minimal/measurable residual disease (MRD) at transplant. In multivariate analysis, relapse incidence (RI) and leukemia-free survival (LFS) were negatively affected by concomitant FLT3-ITD mutation (HR 1.66 p = 0.0001, and HR 1.53, p < 0.0001, respectively), MRD positivity at transplant (HR 2.18, p < 10(-5) and HR 1.71, p < 10(-5), respectively), and transplant in CR2 (HR 1.36, p = 0.026, and HR 1.26, p = 0.033, respectively), but positively affected by Karnofsky score >= 90 (HR 0.74, p = 0.012, and HR 0.7, p = 0.0002, respectively). Overall survival (OS) was also negatively influenced by concomitant FLT3-ITD (HR 1.6, p = 0.0001), MRD positivity at transplant (HR 1.61, p < 10(-5)), and older age (HR 1.22 per 10 years, p < 0.0001), but positively affected by matched sibling donor (unrelated donor: HR 1.35, p = 0.012; haploidentical donor: HR 1.45, p = 0.037) and Karnofsky score >= 90 (HR 0.73, p = 0.004). These results highlight the independent and significant role of FLT3-ITD, MRD status, and disease status on posttransplant outcomes in patients with NPM1-mutated AML allowing physicians to identify patients at risk of relapse who may benefit from posttransplant prophylactic interventions.

Published
2022
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50. Exercise reduces the protein abundance of TXNIP and its interacting partner REDD1 in skeletal muscle: potential role for a PKA-mediated mechanism

Author

Alec B. Chaves, Edwin R. Miranda, Jacob T. Mey, Brian K. Blackburn, Kelly N. Z. Fuller, Blaise Stearns, Andrew Ludlow, David L. Williamson, Joseph A. Houmard, and Jacob M. Haus

Subjects
Physiology, Physiology (medical), Humans, Insulin, Carrier Proteins, Muscle, Skeletal, Exercise, Oxidation-Reduction, Signal Transduction, Transcription Factors, Research Article
Abstract

Thioredoxin-interacting protein (TXNIP) negatively effects the redox state and growth signaling via its interactions with thioredoxin (TRX) and regulated in development and DNA damage response 1 (REDD1), respectively. TXNIP expression is downregulated by pathways activated during aerobic exercise (AE), via posttranslational modifications (PTMs; serine phosphorylation and ubiquitination). The purpose of this investigation was to determine the effects of acute AE on TXNIP expression, posttranslational modifications, and its interacting partners, REDD1 and TRX. Fifteen healthy adults performed 30 min of aerobic exercise (80% V̇o(2max)) with muscle biopsies taken before, immediately following, and 3 h following the exercise bout. To explore potential mechanisms underlying our in vivo findings, primary human myotubes were exposed to two models of exercise, electrical pulse stimulation (EPS) and palmitate-forskolin-ionomycin (PFI). Immediately following exercise, TXNIP protein decreased, but returned to preexercise levels 3 h after exercise. These results were replicated in our PFI exercise model only. Although not statistically significant, there was a trending main effect in serine-phosphorylation status of TXNIP (P = 0.07) immediately following exercise. REDD1 protein decreased 3 h after exercise. AE had no effect on TRX protein expression, gene expression, or the activity of its reducing enzyme, thioredoxin reductase. Consequently, AE had no effect on the TRX: TXNIP interaction. Our results indicate that AE leads to acute reductions in TXNIP and REDD1 protein expression. However, these changes did not result in alterations in the TRX: TXNIP interaction and could not be entirely explained by alterations in TXNIP PTMs or changes in TRX expression or activity. NEW & NOTEWORTHY Aerobic exercise is an effective tool in the prevention and treatment of several chronic metabolic diseases. However, the mechanisms through which these benefits are conferred have yet to be fully elucidated. Our data reveal a novel effect of aerobic exercise on reducing the protein expression of molecular targets that negatively impact redox and insulin/growth signaling in skeletal muscle. These findings contribute to the expanding repository of molecular signatures provoked by aerobic exercise.

Published
2023

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