Title Participants "Interalveolar pore morphology in (pre-)COPD stages and associations with small airways" "Stijn Verleden, Therese Lapperre, Annemiek Snoeckx, Wen Wen, Suresh Krishnan Yogeswaran, Geert M. Verleden, Veronique Verplancke, Reinier R.L. Wener, Senada Koljenovic, Dieter Peeters, Jeroen Hendriks" "The combined effect of systemic antibiotics and proton pump inhibitors on Clostridioides difficile infection and recurrence" "Nele Moreels, Annelies Boven, Oswaldo Gressani, Fredrik L. Andersson, Erika Vlieghe, Steven Callens, Lars Engstrand, Johanna Simin, Nele Brusselaers" "Background Antibiotics and proton pump inhibitors (PPI) are recognized risk factors for acquisition and recurrence of Clostridioides difficile infection (CDI), yet combined effects remain unclear.Objectives To assess the short- and long-term effects of antibiotics and PPIs on CDI risk and recurrence.Methods Population-based study including all 43 152 patients diagnosed with CDI in Sweden (2006-2019), and 355 172 matched population controls without CDI. The impact of antibiotics and PPIs on CDI risk and recurrence was explored for recent (0-30 days) and preceding (31-180 days) use prior to their first CDI diagnosis, using multivariable conditional logistic regression presented as odds ratios (ORs) and 95% confidence interval, adjusted for demographics, comorbidities and other drugs.Results Compared to controls, the combined effect of recent PPIs and antibiotics [ORAB+PPI = 17.51 (17.48-17.53)] on CDI risk was stronger than the individual effects [ORAB = 15.37 (14.83-15.93); ORPPI = 2.65 (2.54-2.76)]. Results were less pronounced for exposure during the preceding months. Dose-response analyses showed increasing exposure correlated with CDI risk [recent use: ORAB = 6.32 (6.15-6.49); ORPPI = 1.65 (1.62-1.68) per prescription increase]. Compared to individuals without recurrence (rCDI), recent [ORAB = 1.30 (1.23-1.38)] and preceding [ORAB = 1.23 (1.16-1.31); ORPPI = 1.12 (1.03-1.21)] use also affected the risk of recurrence yet without significant interaction between both. Recent macrolides/lincosamides/streptogramins; other antibacterials including nitroimidazole derivates; non-penicillin beta lactams and quinolones showed the strongest association with CDI risk and recurrence, particularly for recent use. PPI use, both recent and preceding, further increased the CDI risk associated with almost all antibiotic classes.Results Compared to controls, the combined effect of recent PPIs and antibiotics [ORAB+PPI = 17.51 (17.48-17.53)] on CDI risk was stronger than the individual effects [ORAB = 15.37 (14.83-15.93); ORPPI = 2.65 (2.54-2.76)]. Results were less pronounced for exposure during the preceding months. Dose-response analyses showed increasing exposure correlated with CDI risk [recent use: ORAB = 6.32 (6.15-6.49); ORPPI = 1.65 (1.62-1.68) per prescription increase]. Compared to individuals without recurrence (rCDI), recent [ORAB = 1.30 (1.23-1.38)] and preceding [ORAB = 1.23 (1.16-1.31); ORPPI = 1.12 (1.03-1.21)] use also affected the risk of recurrence yet without significant interaction between both. Recent macrolides/lincosamides/streptogramins; other antibacterials including nitroimidazole derivates; non-penicillin beta lactams and quinolones showed the strongest association with CDI risk and recurrence, particularly for recent use. PPI use, both recent and preceding, further increased the CDI risk associated with almost all antibiotic classes.Conclusion Recent and less recent use of PPIs and systemic antibiotics was associated with an increased risk of CDI, particularly in combination." "Diagnosing viral infections through T cell receptor sequencing of activated CD8+ T cells" "Alexandra Vujkovic, My Ha, Tessa de Block, Lida van Petersen, Isabel Brosius, Caroline Theunissen, Sabrina van Ierssel, Esther Bartholomeus, Wim Adriaensen, Guido Vanham, George Elias, Pierre Van Damme, Vigor Van Tendeloo, Philippe Beutels, Maartje van Frankenhuijsen, Erika Vlieghe, Benson Ogunjimi, Kris Laukens, Pieter Meysman, Koen Vercauteren" "T cell-based diagnostic tools identify pathogen exposure, but lack differentiation between recent and historic exposures in acute infectious diseases. Here, T cell receptor (TCR) RNA sequencing was performed on HLADR+/CD38+ CD8+ T cell subsets of hospitalized COVID-19 patients (n = 30) and healthy controls (n = 30; ten of whom had previously been exposed to SARS-CoV-2). CDR3α and CDR3β TCR regions were clustered separately before epitope specificity annotation using a database of SARS-CoV-2 associated CDR3α and CDR3β sequences corresponding to >1000 SARS-CoV-2 epitopes. The depth of the SARS-CoV-2 associated CDR3α/β sequences differentiated COVID-19 patients from the healthy controls with a receiver operating characteristic curve (ROC) area under the curve (AUC) of 0.84 ± 0.10. Hence, annotating TCR sequences of activated CD8+ T cells can be used to diagnose an acute viral infection and discriminate it from historic exposure. In essence, this work presents a new paradigm of applying the T cell repertoire to accomplish TCR-based diagnostics." "Implementation of the advanced HIV disease care package with point-of-care CD4 testing during tuberculosis case finding" "Tinne Gils, Mashaete Kamele, Thandanani Madonsela, Shannon Bosman, Thulani Ngubane, Philip Joseph, Klaus Reither, Moniek Bresser, Erika Vlieghe, Tom Decroo, Irene Ayakaka, Lutgarde Lynen, Alastair Van Heerden" "During TB-case finding, we assessed the feasibility of implementing the advanced HIV disease (AHD) care package, including VISITECT CD4 Advanced Disease (VISITECT), a semiquantitative test to identify a CD4" "Clostridioides difficile infection-associated cause-specific and all-cause mortality" "Annelies Boven, Erika Vlieghe, Lars Engstrand, Fredrik L. Andersson, Steven Callens, Nele Brusselaers" "Objectives: Clostridioides difficile infection (CDI) is a common healthcare-associated infection and leading cause of gastroenteritis-related mortality worldwide. However, data on CDI-associated mortality are scarce. We aimed to examine the association between CDI and all-cause and cause-specific mortality. We additionally explored contributing causes of mortality, including recurrent CDI, hospital-or community acquired CDI, chronic comorbidities, and age. Methods: This nationwide population-based cohort study (from 2006 to 2019) compared individuals with CDI with the entire Swedish background population using standardized mortality ratios. In addition, a matched-cohort design (1:10), utilizing multivariable Poisson-regression models, provided incidence rate ratios (IRRs) with 95% CIs. Results: This study included 43 150 individuals with CDI and 355 172 controls. In total, 69.7% were >65 years, and 54.9% were female. CDI was associated with a 3-to 7-fold increased mortality rate (IRR = 3.5, 95% CI: 3.3-3.6; standardized mortality ratio = 6.8, 95% CI: 6.7-6.9) compared with the matched controls and Swedish background population, respectively. Mortality rates were highest for hospital-acquired CDI (IRR = 2.4, 95% CI: 1.9-3.2) and during the first CDI episode (IRR = 0.2, 95% CI: 0.2-0.3 for recurrent versus first CDI). Individuals with CDI had more chronic comorbidities than controls, yet mortality remained higher among CDI cases even after adjustment and stratification for comorbidity; CDI was associated with increased mortality (IRR = 6.1, 95% CI: 5.5-6.8), particularly among those without any chronic comorbidities. Discussion: CDI was associated with elevated all-cause and cause-specific mortality, despite possible confounding by ill health. Mortality rates were consistently increased across sexes, all age groups, and comorbidity groups. Annelies Boven, Clin Microbiol Infect 2023;29:1424 (c) 2023 The Author(s). Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/)." "Pilot study to evaluate tools to collect pathologist annotations for validating machine learning algorithms" "Katherine Elfer, Sarah Dudgeon, Victor Garcia, Kim Blenman, Evangelos Hytopoulos, Si Wen, Xiaoxian Li, Amy Ly, Bruce Werness, Manasi S. Sheth, Mohamed Amgad, Rajarsi Gupta, Joel Saltz, Matthew G. Hanna, Anna Ehinger, Dieter Peeters, Roberto Salgado, Brandon D. Gallas" "Purpose: Validation of artificial intelligence (AI) algorithms in digital pathology with a reference standard is necessary before widespread clinical use, but few examples focus on creating a reference standard based on pathologist annotations. This work assesses the results of a pilot study that collects density estimates of stromal tumor-infiltrating lymphocytes (sTILs) in breast cancer biopsy specimens. This work will inform the creation of a validation dataset for the evaluation of AI algorithms fit for a regulatory purpose. Approach: Collaborators and crowdsourced pathologists contributed glass slides, digital images, and annotations. Here, ""annotations"" refer to any marks, segmentations, measurements, or labels a pathologist adds to a report, image, region of interest (ROI), or biological feature. Pathologists estimated sTILs density in 640 ROIs from hematoxylin and eosin stained slides of 64 patients via two modalities: an optical light microscope and two digital image viewing platforms. Results: The pilot study generated 7373 sTILs density estimates from 29 pathologists. Analysis of annotations found the variability of density estimates per ROI increases with the mean; the root mean square differences were 4.46, 14.25, and 26.25 as the mean density ranged from 0% to 10%, 11% to 40%, and 41% to 100%, respectively. The pilot study informs three areas of improvement for future work: technical workflows, annotation platforms, and agreement analysis methods. Upgrades to the workflows and platforms will improve operability and increase annotation speed and consistency. Conclusions: Exploratory data analysis demonstrates the need to develop new statistical approaches for agreement. The pilot study dataset and analysis methods are publicly available to allow community feedback. The development and results of the validation dataset will be publicly available to serve as an instructive tool that can be replicated by developers and researchers. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 International License." "Use of WATCH antibiotics prior to presentation to the hospital in rural Burkina Faso" "Daniel Valia, Brecht Ingelbeen, Berenger Kabore, Ibrahima Karama, Marjan Peeters, Palpouguini Lompo, Erika Vlieghe, Annelies Post, Janneke Cox, Quirijn de Mast, Annie Robert, Marianne A.B. van der Sande, Hector Rodriguez Villalobos, Andre van der Ven, Halidou Tinto, Jan Jacobs" "Background In low- and middle-income countries, the prevalence of antimicrobial resistance (AMR) is increasing. To control AMR, WHO recommends monitoring antibiotic use, in particular Watch antibiotics. These are critically important antibiotics, with restricted use because at risk of becoming ineffective due to increasing AMR. We investigated pre-hospital antibiotic use in rural Burkina Faso. Methods During 2016-2017, we collected data from patients aged > 3 months presenting with severe acute fever to the rural hospital of Nanoro Health District, Burkina Faso, including antibiotic use in the two weeks prior to consultation or hospitalization. We analysed reported antibiotic use by applying the WHO Access, Watch, Reserve classification. Results Of 920 febrile participants (63.0% 14 year olds (51.1%) compared to those 0-14 year old (30.7%, p < 0.001) and among referrals from the primary health care centers (42.2%) compared to self-referred patients (28.1%, p = 0.004). Most frequently reported Watch antibiotics were ceftriaxone (114, 71.7%) and ciprofloxacin (32, 20.1%). Conclusion The reported frequent use of Watch group antibiotics among febrile patients prior to presentation to the hospital in rural Burkina Faso highlights the need to develop targeted interventions to improve antibiotic use in community settings as part of strengthening antibiotic stewardship in low- and middle-income countries. This should include facilitating referral, access to qualified prescribers and diagnostic tools in rural primary health care centers. Trial registration ClinicalTrials.gov identifier: NCT02669823. Registration date was February 1, 2016." "Pandemics and other health crises" "Gianluca Quaglio, Luca Ragazzoni, Isabel De la Mata, Raed Arafat, Sabine De Muynck, Erika Vlieghe, Petra Claes" "Once an emergency has passed, general attention typically returns to dealing with day-to-day system management, and the opportunity to learn from the crisis and improve is missed. Lessons from the coronavirus disease 2019 (COVID-19) crisis must be learned, and the necessary changes made at all levels, both in terms of improving collaboration and strengthening health systems. This special report provides the conclusion of a workshop held in the European Parliament (EP) in Brussels, Belgium. The event explored the modalities of response and preparation to the COVID-19 pandemic, and to health crises in general. The workshop considered actions at different levels: international organizations (global level), European Union (EU) Member States ([MS] national level), and health services (local level). It provided an opportunity to look back at several initiatives taken during the pandemic, and to draw inspiration from them." "The emergence of travel-related infections in critical care units" "Pieter-Jan Herten, Erika Vlieghe, Emmanuel Bottieau, Eric Florence, Philippe Jorens" "Several tropical or geographically confined infectious diseases may lead to organ failure requiring management in an intensive care unit (ICU), both in endemic low- and middle-income countries where ICU facilities are increasingly being developed and in (nonendemic) high-income countries through an increase in international travel and migration. The ICU physician must know which of these diseases may be encountered and how to recognize, differentiate, and treat them. The four historically most prevalent ""tropical "" diseases (malaria, enteric fever, dengue, and rickettsiosis) can present with single or multiple organ failure in a very similar manner, which makes differentiation based solely on clinical signs very difficult. Specific but frequently subtle symptoms should be considered and related to the travel history of the patient, the geographic distribution of these diseases, and the incubation period. In the future, ICU physicians may also be more frequently confronted with rare but frequently lethal diseases, such as Ebola and other viral hemorrhagic fevers, leptospirosis, and yellow fever. No one could have foreseen the worldwide 2019-up to now coronavirus disease 2019 (COVID-19) crisis caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was initially spread by travel too. In addition, the actual pandemic due to SARS-CoV-2 reminds us of the actual and potential threat of (re)-emerging pathogens. If left untreated or when treated with a delay, many travel-related diseases remain an important cause of morbidity and even mortality, even when high-quality critical care is provided. Awareness and a high index of suspicion of these diseases is a key skill for the ICU physicians of today and tomorrow to develop." "Hospital antibiotic prescribing patterns in adult patients according to the WHO Access, Watch and Reserve classification (AWaRe)" "Ann Versporten, Erika Vlieghe, Herman Goossens, Andi Koraqi, Iris Hoxha, Silva Tafaj, Wanda Cornistein, Rodolfo Quiros, Martin Hojman, Lilit Ghazaryan, Kylie Horne, Kelly Cairns, Fiona Doukas, Thomas Gottlieb, Erica Sermijn, Katia Verhamme, Christiane Brands, Bruno Van Herendael, Lorenzo Filippin, Wouter Vandewal, Deborah Konopnicki, Evelyne Maillart, Liliana Teixeira Lopes, Pauline Papin, Ilse Smits, Hilde Jansens, Sofie Bartholomeus, Anne-Marie Van den Abeele, Sophia Steyaert, Anne Piette, Franky Buyle, Reinoud Cartuyvels, Stijn Jonckheere, Ingrid Wybo, Lorenz Vanneste, Delphine Mathieu, Eric Firre, Veerle Westelinck, Philippe Gadisseux, Thierry Dugernier, Kristof Bafort, Viviane Gonissen, Vanessa Vanderper, Patrick Gabriels, Frank Weekers, Philippe Michel, Ann Van Liedekerke, Michiel Costers, Boudewijn Catry, Amela Dedeic-Ljubovic, Ana C. Gales, Ana Paula Matos Porto, Silvia Figueiredo Costa, Emma Keuleyan, Apollinaire Beidi, Youssouph Cissohko, Habsatou Blakwe, Ngassa Batchaya Basile, Greg J. German, Sarah Lutes, Jennifer Boswell, Dominik Mertz, Tuyen Nguyen, Timothy MacLaggan, Daniel Landry, Anita Ang, Daniel J.G. Thirion, Charles Frenette, Yannick Émond, Jacqueline Roberts, Sandra Chang, Justin Kosar, Louis Valiquette, Ginette Dutrisac, Kevin Afra, Allison McGeer, Marie Carrier, Jennifer Grant, Jaime Labarca, Camila Carvajal, HongYi Lin, Qiang Wang, Jing Yang, Wenjie Yang, Jorge A. Cortes, Juan Villalobos-Vindas, Carlos Ramírez-Valverde, Jasminka Horvatic, Irina Pristas, Niki Paphitou, Maija-Liisa Rummukainen, Antoine Froissart, Philippe Vanhems, Karaman Pagava, Irma Korinteli, Tobias Brandt, Johannes Gaertner, Anthony Enimil, Emmanuel Roilides, Edit Hajdú, Sharmila Sengupta, Sanjeev Singh, Priyanka Patil, Aruna Poojary, Jafar Soltani, Gholamreza Pouladfar, Zahra Jafarpour, Cyrus Alinia, Hadi Ameen, David Fitzgerald, Mical Paul, Yasmin Maor, Jacob Strahilevitz, Michal Chowers, Elizabeth Temkin, Arnoldo Luca, Noriomi Ishibashi, Yoshiaki Gu, Feras Darwish Elhajji, Aizhan Karabukayeva, Denis Raka, Baktygul Kambaralieva, Lelde Zarakauska, Peter Zarb, Blanca Estela Hernandez Chena, Esteban Gonzalez-Diaz, JuanCarlos Corona-Meléndez, Darwin Stalin Torres Erazo, Suria Elizabeth Loza-Jalil, Julio Molina, Jose Antonio Candelas, Gordana Mijovic, Natasa Duborija-Kovacevic, Eefje Jong, Jan Kluytmans, Erika van Elzakker, Valentijn Schweitzer, Nicola Davies, Kenneth Iregbu, Philip Nwajiobi-Princewill, Ifeyinwa Nwafia, Temitayo Fasuyi, Aaron Aboderin, Charles John Elikwu, Abayomi Fadeyi, Olafoyekemi Ola-Bello, Oyinlola Oduyebo, Akin Nelson Adedosu, Agantem Ekuma, Erjona Shaqiri, Zikria Saleem, Mari Rose De Los Reyes, Luis Tavares, Nam Joong Kim, Svetlana Rachina, Alwaleed R. Alharthi, Mushira Enani, Osama Faried, Mohamed Mirghani, Biljana Carevic, Lili Radulovic, Gorana Dragovac, Sock Hoon Tan, Jantjie Taljaard, Vindana Chibabhai, Jennifer Joiner, Juan Jose Caston, María Núñez-Núñez, Francisco Javier Martínez-Marcos, Guillermo Ojeda-Burgos, Maria Dolores Menendez, Pilar Retamar, Juan E. Corzo, Pinyo Rattanaumpawan, Mounerou Salou, Basma Mnif, Ahsen Oncul, Peter Ahabwe Babigumira, James Olweny, Emily Marshall, Ann McCorry, Mamoon Aldeyab, Priya Khanna, Cairine Gormley, Sara Maloney, Mandelin Cooper, Laura Blackburn, Mallory Gessner-Wharton, Lam Vu, Nickie Greer, Gerard Gawrys, Lisha Kronmann, Edgar Rios, Melissa Hudson, David A. Lindholm" "Objectives: The WHO Access, Watch and Reserve (AWaRe) classification has been developed to support countries and hospitals in promoting rational use of antibiotics while improving access to these essential medicines. We aimed to describe patterns of worldwide antibiotic use according to the AWaRe classification in the adult inpatient population. Methods: The Global Point Prevalence Survey on Antimicrobial Consumption and Resistance (Global-PPS) collects hospital antibiotic use data using a standardized PPS methodology. Global-PPS 2015, 2017 and 2018 data, collected by 664 hospitals in 69 countries, were categorized into AWaRe groups to calculate proportional AWaRe use, Access-to-Watch ratios and the most common indications for treatment with selected Watch antibiotics. Only prescriptions for systemic antibiotics on adult inpatient wards were analysed. Results: Regional Access use ranged from 28.4% in West and Central Asia to 57.7% in Oceania, whereas Watch use was lowest in Oceania (41.3%) and highest in West and Central Asia (66.1%). Reserve use ranged from 0.03% in sub-Saharan Africa to 4.7% in Latin America. There were large differences in AWaRe prescribing at country level. Watch antibiotics were prescribed for a range of very different indications worldwide, both for therapeutic and prophylactic use. Conclusions: We observed considerable variations in AWaRe prescribing and high use of Watch antibiotics, particularly in lower- and upper-middle-income countries, followed by high-income countries. The WHO AWaRe classification has an instrumental role to play in local and national stewardship activities to assess prescribing patterns and to inform and evaluate stewardship activities."