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An inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor that occurs predominantly in children and young adults. Etiology remains unclear. But based on the frequent detection of chromosomic alterations, especially near the anaplastic lymphoma kinase (ALK) gene, IMT is now considered to be a true neoplasm. In addition, the possible aggressive behavior, and the ability to metastasize suggest at least an intermediate malignant potential. Surgery remains the treatment of choice, but the use of chemotherapy, nonsteroidal anti-inflammatory drugs, immunotherapy, and targeted therapy are reported. We describe a case of a pulmonary IMT in a 6-year-old boy with an incidental finding of a lesion in the right upper lobe. A video-assisted thoracoscopic right upper lobectomy with lymph node resection was performed. Microscopic examination confirmed the diagnosis of IMT with the nodule showing spindle cells in a background of plasma cells. ALK immunohistochemical expression was negative., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Human parainfluenza virus type 3 (HPIV-3) can cause severe respiratory tract infections. There are no convenient small-animal infection models. Here, we show viral replication in the upper and lower airways of AG129 mice (double IFNα/β and IFNγ receptor knockout mice) upon intranasal inoculation. By multiplex fluorescence RNAscope and immunohistochemistry followed by confocal microscopy, we demonstrate viral tropism to ciliated cells and club cells of the bronchiolar epithelium. HPIV-3 causes a marked lung pathology. No virus transmission of the virus was observed by cohousing HPIV-3-infected AG129 mice with other mice. Oral treatment with GS-441524, the parent nucleoside of remdesivir, reduced infectious virus titers in the lung, with a relatively normal histology. Intranasal treatment also affords an antiviral effect. Thus, AG129 mice serve as a robust preclinical model for developing therapeutic and prophylactic strategies against HPIV-3. We suggest further investigation of GS-441524 and its prodrug forms to treat HPIV-3 infection in humans., (© 2024. The Author(s).)

Research on metastatic cancer has been hampered by limited sample availability. Here we present the breast cancer post-mortem tissue donation program UPTIDER and show how it enabled sampling of a median of 31 (range: 5-90) metastases and 5-8 liquids per patient from its first 20 patients. In a dedicated experiment, we show the mild impact of increasing time after death on RNA quality, transcriptional profiles and immunohistochemical staining in tumor tissue samples. We show that this impact can be counteracted by organ cooling. We successfully generated ex vivo models from tissue and liquid biopsies from distinct histological subtypes of breast cancer. We anticipate these and future findings of UPTIDER to elucidate mechanisms of disease progression and treatment resistance and to provide tools for the exploration of precision medicine strategies in the metastatic setting., (© 2024. The Author(s).)

Breast cancer associated with osteoclast-like giant cells (OGCs) refers to a morphological pattern of invasive breast carcinoma of non-special type. Their presence is sometimes subtle, but OGCs can be appreciated both histologically and immunohistochemically. The origin of OGCs as well as their implication for prognosis remain debated. We describe the case of a 65-year-old woman, wherein the presence of OGCs in the fine-needle aspiration cytology of a metastatic axillary lymph node suggested the final diagnosis on histology. The differential diagnosis is broad, and here we provide evidence for strict cytological-histological correlation when dealing with unusual breast lesions., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Veekmans et al.)

Background: Pleural neoplasms are rare and can be subdivided into pleural metastasis and primary pleural neoplasms. Non-mesothelioma primary pleural neoplasms are a diverse group of extremely rare pathologies., Case Presentation: In this case series, we describe the presentation and management of two rare primary pleural neoplasms. A first case describes a primary pleural yolk sac tumor treated with neoadjuvant chemotherapy, extended pleurectomy decortication, and hyperthermic intrathoracic chemotherapy. In a second case we describe the management of a primary pleural synovial sarcoma by neoadjuvant chemotherapy and extrapleural pneumonectomy. A complete resection was obtained in both cases and the post-operative course was uncomplicated. No signs of tumor recurrence were noted during follow-up in the first patient. In the second patient a local recurrence was diagnosed 6 months after surgery., Conclusion: Neo-adjuvant chemotherapy followed by extensive thoracic surgery, including hyperthermic intrathoracic chemotherapy, is a feasible treatment strategy for non-mesothelioma primary pleural neoplasms, but careful follow-up is required., (© 2024. The Author(s).)

Background: Chronic lung allograft dysfunction (CLAD) encompasses three main phenotypes: bronchiolitis obliterans syndrome (BOS), restrictive allograft syndrome (RAS) and a Mixed phenotype combining both pathologies. How the airway structure in its entirety is affected in these phenotypes is still poorly understood., Methods: A detailed analysis of airway morphometry was applied to gain insights on the effects of airway remodelling on the distribution of alveolar ventilation in end-stage CLAD. Ex vivo whole lung μCT and tissue-core μCT scanning of six control, six BOS, three RAS and three Mixed explant lung grafts (9 male, 9 female, 2014-2021, Leuven, Belgium) were used for digital airway reconstruction and calculation of airway dimensions in relation to luminal obstructions., Findings: BOS and Mixed explants demonstrated airway obstructions of proximal bronchioles (starting at generation five), while RAS explants particularly had airway obstructions in the most distal bronchioles (generation >12). In BOS and Mixed explants 76% and 84% of bronchioles were obstructed, respectively, while this was 22% in RAS. Bronchiolar obstructions were mainly caused by lymphocytic inflammation of the airway wall or fibrotic remodelling, i.e. constrictive bronchiolitis. Proximal bronchiolectasis and imbalance in distal lung ventilation were present in all CLAD phenotypes and explain poor lung function and deterioration of specific lung function parameters., Interpretation: Alterations in the structure of conducting bronchioles revealed CLAD to affect alveolar ventilatory distribution in a regional fashion. The significance of various obstructions, particularly those associated with mucus, is highlighted., Funding: This research was funded with the National research fund Flanders (G060322N), received by R.V., Competing Interests: Declaration of interests JK and VG and MV are junior research fellows of the Research Foundation Flanders (FWO; 1198920N and 1102020N and 1SE433N). MV received compensation from Sanofi for attending the ERS 2023 congress. GPLA is a supported by an European Respirology Society Clinical Fellowship Grant. SB is supported by the Paul Corris International Clinical Research Training Scholarship. LJDS (De Sadeleer) is supported by the European Union's Horizon Europe research and innovation programme as a Marie Sklodowska-Curie actions postdoctoral fellowship (grant agreement No. 101066289)., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: SARS-CoV-2-neutralizing antibodies (nABs) showed great promise in the early phases of the COVID-19 pandemic. The emergence of resistant strains, however, quickly rendered the majority of clinically approved nABs ineffective. This underscored the imperative to develop nAB cocktails targeting non-overlapping epitopes., Methods: Undertaking a nAB discovery program, we employed a classical workflow, while integrating artificial intelligence (AI)-based prediction to select non-competing nABs very early in the pipeline. We identified and in vivo validated (in female Syrian hamsters) two highly potent nABs., Findings: Despite the promising results, in depth cryo-EM structural analysis demonstrated that the AI-based prediction employed with the intention to ensure non-overlapping epitopes was inaccurate. The two nABs in fact bound to the same receptor-binding epitope in a remarkably similar manner., Interpretation: Our findings indicate that, even in the Alphafold era, AI-based predictions of paratope-epitope interactions are rough and experimental validation of epitopes remains an essential cornerstone of a successful nAB lead selection., Funding: Full list of funders is provided at the end of the manuscript., Competing Interests: Declaration of interests Ghent University has filed for patent protection on the antibody sequences described herein, and D.D.A., M.W., R.W., W.W., S.G. and L.V. are named as co-inventors on this patent (European Patent Application: 21186206.5). A.P. is employee of the MAbSilico, H.R. holds a patent regarding neutralizing VHH antibodies binding the Spike RBD (PCT/EP2021/052885) and has filed a priority application for neutralizing VHH antibodies binding Spike S2 (EP 23160838.1). X.S. is a recipient of FWO research project COVID-19 (G0G4920N) and FWO-FNRS project VIREOS (EOS ID: 30981113) grants., (Copyright © 2023. Published by Elsevier B.V.)

Since the emergence of the first omicron SARS-CoV-2 variant at the end of 2021, several sub-variants have evolved and become predominant in the human population, showing enhanced transmissibility and ability to (partly) escape the adaptive immune response. The XBB sub-variants (e.g., EG.5.1) have become globally dominant. Besides the XBB sub-variants, a phylogenetically distinct variant, i.e., BA.2.86, is also circulating; it carries several mutations in the spike protein as compared to its parental BA.2 variant. Here, we explored the infectivity of the BA.2.86 and EG.5.1 sub-variants compared to the preceding BA.5 sub-variant in Syrian hamsters. Such preclinical models are important for the evaluation of updated vaccine candidates and novel therapeutic modalities. Following intranasal infection with either variant, throat swabs and lung samples were collected on days 3 and 4 post infection. No significant differences in viral RNA loads in throat swabs were observed between these sub-variants. However, the infectious virus titers in the lungs of EG.5.1- and BA.2.86-infected animals were significantly lower compared to the BA.5-infected ones. The lung pathology scores of animals infected with EG.5.1 and BA.2.86 were also markedly lower than that of BA.5 sub-variant. Together, we show that EG.5.1 and BA.2.86 sub-variants exhibit an attenuated replication in hamsters' lungs as compared to the BA.5 sub-variant.

The development of novel optimized vaccines against coronavirus disease 2019 (COVID-19) that are capable of controlling the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and the appearance of different variants of concern (VoC) is needed to fully prevent the transmission of the virus. In the present study, we describe the enhanced immunogenicity and efficacy elicited in hamsters by a modified vaccinia virus Ankara (MVA) vector expressing a full-length prefusion-stabilized SARS-CoV-2 spike (S) protein [termed MVA-S(3P)]. Hamsters vaccinated with one or two doses of MVA-S(3P) developed high titers of S-binding IgG antibodies and neutralizing antibodies against the ancestral Wuhan SARS-CoV-2 virus and VoC beta, gamma, and delta, as well as against omicron, although with a somewhat lower neutralization activity. After SARS-CoV-2 challenge, vaccinated hamsters did not lose body weight as compared to matched placebo (MVA-WT) controls. Consistently, vaccinated hamsters exhibited significantly reduced viral RNA in the lungs and nasal washes, and no infectious virus was detected in the lungs in comparison to controls. Furthermore, almost no lung histopathology was detected in MVA-S(3P)-vaccinated hamsters, which also showed significantly reduced levels of proinflammatory cytokines in the lungs compared to unvaccinated hamsters. These results reinforce the use of MVA-S(3P) as a vaccine candidate against COVID-19 in clinical trials., Competing Interests: Authors DM, EP, and ER were employed by the company Biofabri. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Abdelnabi, Pérez, Astorgano, Albericio, Kerstens, Thibaut, Coelmont, Weynand, Labiod, Delgado, Montenegro, Puentes, Rodríguez, Neyts, Dallmeier, Esteban and García-Arriaza.)