Review
Respiratory System
Cormac McCarthy, Michael P. Keane
Summary: The past two years have brought unforeseen challenges to pulmonary medicine, but advancements in the care and understanding of interstitial lung disease (ILD) have not been hindered. Studies published in 2021 have contributed to improved guidelines, a better understanding of antifibrotics in fibrosing ILDs, prognostic indicators, and novel biomarkers. This concise contemporary review summarizes the important studies and highlights their relevance and impact on ILD management and knowledge.
Article
Critical Care Medicine
Penghui Yang, Qun Luo, Xinlu Wang, Qi Fang, Zhenli Fu, Jia Li, Yunxin Lai, Xiaobo Chen, Xin Xu, Xiaomin Peng, Kongzhen Hu, Xiaowei Nie, Shaoyu Liu, Jinhe Zhang, Junqi Li, Chenyou Shen, Yingying Gu, Jianping Liu, Jingyu Chen, Nanshan Zhong, Jin Su
Summary: The study investigates the potential use of FAP expression intensity as a quantitative indicator of activated fibroblast quantity in ILD lungs. Multiple experimental methods were used to test FAP expression in human primary lung fibroblasts and clinical lung specimens. FAP-targeted PET/CT imaging was applied to different types of ILD patients. The results reveal that FAP expression is significantly upregulated in the early phase of fibroblast activation in response to profibrotic cytokine, and is closely correlated with fibroblastic foci abundance in ILD patient lung biopsies. Additionally, FAP detection is associated with fibrotic activity in ILDs and may aid in early diagnosis and therapeutic window selection.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Article
Medicine, General & Internal
Hye Jin Jang, Ala Woo, Song Yee Kim, Seung Hyun Yong, Youngmok Park, Kyungsoo Chung, Su Hwan Lee, Ah Young Leem, Sang Hoon Lee, Eun Young Kim, Ji Ye Jung, Young Ae Kang, Young Sam Kim, Moo Suk Park
Summary: This study aimed to identify risk factors for mortality and compare the clinical characteristics of patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). The study found that approximately 10% of SSc-ILD patients showed disease progression, and ILD was detected within less than five years from the first visit. Therefore, careful monitoring of symptoms and signs from an early stage and long-term surveillance are necessary.
ANNALS OF MEDICINE
(2023)
Article
Chemistry, Multidisciplinary
Shiyi Zhou, Zipeng Zhen, Amy V. Paschall, Lijun Xue, Xueyuan Yang, Anne-Gaelle Bebin Blackwell, Zhengwei Cao, Weizhong Zhang, Mengzhe Wang, Yong Teng, Gang Zhou, Zibo Li, Fikri Y. Avci, Wei Tang, Jin Xie
Summary: This study developed a photodynamic therapy approach using nanoparticles specifically targeting FAP, which efficiently eradicated CAFs in tumors and induced anti-cancer immunity in murine models. Interestingly, the treatment not only elicited cellular immunity against cancer cells, but also stimulated an anti-CAFs immunity, as supported by adoptive cell transfer study.
ADVANCED FUNCTIONAL MATERIALS
(2021)
Review
Respiratory System
David J. F. Smith, R. Gisli Jenkins
Summary: Novel genetic associations for idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis have been identified. Understanding underlying mechanisms and discovering circulating biomarkers may lead to future treatments. Deep learning and machine learning can improve accuracy in interpreting CT scans. Novel treatments have been successful in phase 2 trials. COVID-19 hospitalization is linked to residual lung abnormalities. Inequalities exist in access to interstitial lung disease specialist care.
Article
Radiology, Nuclear Medicine & Medical Imaging
Yuchun Wei, Kai Cheng, Zheng Fu, Jinsong Zheng, Zhengshuai Mu, Chenglong Zhao, Xiaoli Liu, Shijie Wang, Jinming Yu, Shuanghu Yuan
Summary: This study investigated the use of [F-18]AlF-NOTA-FAPI-04 PET/CT imaging to evaluate tracer uptake in primary and metastatic lesions of lung cancer, revealing differences in FAP expression among metastases, with the highest expression specifically in bone metastases. This technique may be valuable for distinguishing different pathological types of lung cancer.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2022)
Article
Biochemistry & Molecular Biology
Laura Gilardi, Lighea Simona Airo Farulla, Emre Demirci, Ilaria Clerici, Emanuela Omodeo Sale, Francesco Ceci
Summary: The tumor microenvironment (TME) is a complex system that promotes tumorigenesis, with cancer-associated fibroblasts (CAFs) playing a key role. Inhibitors targeting the fibroblast activation protein (FAP) have shown promise for molecular imaging and radio-ligand therapy, particularly in low FDG-avid tumors and unfavorable regions. However, more research is needed to determine the efficacy of this pan-tumoral approach.
Review
Oncology
Angela J. Frank, Ibiayi Dagogo-Jack, Ioana A. Dobre, Sarah Tait, Lana Schumacher, Florian J. Fintelmann, Leah M. Fingerman, Florence K. Keane, Sydney B. Montesi
Summary: Patients with interstitial lung disease (ILD), especially those with pulmonary fibrosis, are at increased risk of developing lung cancer. Managing lung cancer in these patients is challenging as diagnosis can be complicated, surgical resection can exacerbate ILD, radiotherapy and systemic therapies carry increased risk of pneumonitis, and the safety of immunotherapy remains unclear. This review summarizes evidence and discusses considerations for tissue diagnosis, chemotherapy, immunotherapy, radiotherapy, and surgery in this patient population, as well as the importance of a multidisciplinary approach and monitoring ILD progression during lung cancer treatment.
Review
Chemistry, Medicinal
Surachet Imlimthan, Euy Sung Moon, Hendrik Rathke, Ali Afshar-Oromieh, Frank Roesch, Axel Rominger, Eleni Gourni
Summary: The tumor microenvironment (TME) has become a new paradigm of cancer diagnosis and therapy in the past decade, with cancer-associated fibroblasts (CAFs) being identified as critical stromal cells that regulate tumor growth and progression. Research on FAP-based radiopharmaceuticals for visualizing malignancies and delivering theranostic radiopharmaceuticals to the TME has been intensively investigated. This review provides an overview of TME compositions, particularly CAFs and FAP, and their roles in cancer biology, as well as the challenges and requirements for radiolabeled FAP inhibitors in clinical translation.
Article
Oncology
Xinfeng Lin, Yingjie Li, Shuailiang Wang, Yan Zhang, Xuetao Chen, Maomao Wei, Hua Zhu, Aiwen Wu, Zhi Yang, Xuejuan Wang
Summary: This study compared the diagnostic performance of [Ga-68]Ga-FAPI-04 PET/CT and [F-18]F-FDG PET/CT in primary and metastatic colorectal cancer lesions, and found that [Ga-68]Ga-FAPI-04 showed potential as a novel PET/CT tracer. The use of this tracer improved the staging of colorectal cancer and led to optimization or adjustment of treatment decisions.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Wakako Daido, Takeshi Masuda, Nobuki Imano, Naoko Matsumoto, Kosuke Hamai, Yasuo Iwamoto, Yusuke Takayama, Sayaka Ueno, Masahiko Sumii, Hiroyasu Shoda, Nobuhisa Ishikawa, Masahiro Yamasaki, Yoshifumi Nishimura, Shigeo Kawase, Naoki Shiota, Yoshikazu Awaya, Tomoko Suzuki, Soichi Kitaguchi, Kazunori Fujitaka, Yasushi Nagata, Noboru Hattori
Summary: Interstitial lung disease (ILD) is a life-threatening toxicity caused by chemoradiotherapy and durvalumab. In non-small-cell lung cancer patients, pre-existing interstitial lung abnormalities (ILAs) may be independent risk factors for ILD during treatment with durvalumab. Patients with ILAs should be monitored closely for the development of severe ILD during durvalumab therapy.
Review
Biochemistry & Molecular Biology
Joe E. Mouawad, Carol Feghali-Bostwick
Summary: Systemic sclerosis, also known as scleroderma, is an autoimmune disorder that affects the connective tissues and has a high mortality rate. Fibrosis, particularly in the lungs, is a hallmark of the disease and is currently the leading cause of death. Understanding the molecular mechanisms involved in lung fibrosis is essential for developing potential therapies to improve patient outcomes and quality of life.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Paula E. Borgonje, Louise M. Andrews, Gerarda J. M. Herder, John M. H. de Klerk
Summary: This review provides an overview of the available evidence on the use of fibroblast activation protein inhibitor (FAPI) as a tracer for positron emission tomography (PET) in patients with lung cancer. It shows that FAPI PET/CT has a strong diagnostic performance in lung cancer and may have prognostic value.
Article
Engineering, Biomedical
Jaehoon Kim, Hyejin Park, Hyunho Kim, YongTae Kim, Hyun Jeong Oh, Seok Chung
Summary: Tumors create interstitial flow (IF), which allows soluble substances from cancer cells to be transported towards the tumor stroma. Researchers have designed a microfluidic device that mimics one-directional flow of IF to investigate how cancer cells activate and differentiate stromal cells.
ACTA BIOMATERIALIA
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Mengxin Xu, Junyi Chen, Pu Zhang, Jie Cai, Hanbo Song, Zhu Li, Zhibo Liu
Summary: In this study, a FAP-targeted antibody-radionuclide conjugate was developed and evaluated in vitro and in vivo. The conjugate showed rapid and high tumor accumulation with minimal side effects, suggesting its potential for further clinical translation studies.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2023)
Article
Oncology
Mirco Friedrich, Markus Hahn, Julius Michel, Roman Sankowski, Michael Kilian, Niklas Kehl, Manina Guenter, Theresa Bunse, Stefan Pusch, Andreas von Deimling, Wolfgang Wick, Stella E. Autenrieth, Marco Prinz, Michael Platten, Lukas Bunse
Summary: The study reveals that glioma-associated dendritic cells are abundant in human IDHwt and mutant tumors, interacting with other immune cells in the tumor microenvironment. IDH mutations in gliomas result in specifically educated, dysfunctional dendritic cells through paracrine reprogramming of infiltrating monocytes, laying the foundation for combinatorial immunotherapy concepts against IDH mutant gliomas.
Review
Oncology
Julie J. Miller, L. Nicolas Gonzalez Castro, Samuel McBrayer, Michael Weller, Timothy Cloughesy, Jana Portnow, Ovidiu Andronesi, Jill S. Barnholtz-Sloan, Brigitta G. Baumert, Mitchell S. Berger, Wenya Linda Bi, Ranjit Bindra, Daniel P. Cahill, Susan M. Chang, Joseph F. Costello, Craig Horbinski, Raymond Y. Huang, Robert B. Jenkins, Keith L. Ligon, Ingo K. Mellinghoff, L. Burt Nabors, Michael Platten, David A. Reardon, Diana D. Shi, David Schiff, Wolfgang Wick, Hai Yan, Andreas von Deimling, Martin van den Bent, William G. Kaelin, Patrick Y. Wen
Summary: This article discusses the diagnosis and management of IDH-mutant gliomas, as well as new treatment methods and future research directions.
Article
Oncology
Florian Selt, Romain Sigaud, Gintvile Valinciute, Philipp Sievers, Julia Zaman, Clara Alco, Simone Schmid, Heike Peterziel, Jessica W. Tsai, Romain Guiho, Juan Pedro Martinez-Barbera, Stefan Pusch, Jing Deng, Yifan Zhai, Cornelis M. van Tilburg, Martin U. Schuhman, Ahmed E. L. Damaty, Pratiti Bandopadhayay, Christel Herold-Mende, Andreas von Deimling, Stefan M. Pfister, Joan Montero, David Capper, Ina Oehme, Felix Sahm, David T. W. Jones, Olaf Witt, Till Milde
Summary: Our study demonstrates that BCL-XL is critical for the survival of senescent PA tumor cells and provides evidence for the use of clinically available BCL-XL-dependent senolytic agents.
Article
Physiology
Kai Foerster, Hanna Marchi, Sophia Stoecklen, Olaf Dietrich, Harald Ehrhardt, Mark O. Welipultz, Andreas W. Flemmer, Benjamin Schubert, A. Marcus Mall, Birgit Ertl-Wagner, Anne Hillgendroff
Summary: This study developed a novel scoring system using MRI to assess lung structural changes in neonatal chronic lung disease. It showed high reproducibility and disease specificity, and has the potential to be used as a quantifiable endpoint in clinical trials and disease monitoring.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2023)
Article
Pediatrics
Stefanie Theuring, Mascha Kern, Franziska Hommes, Marcus A. A. Mall, Joachim Seybold, Frank P. P. Mockenhaupt, Toivo Glatz, Tobias Kurth
Summary: During the COVID-19 pandemic, children and adolescents worldwide have been disproportionately affected in their psychological health and wellbeing. A cohort study in Germany found that anxiety symptoms among school children decreased from June to August 2021, but increased again in September 2021. Factors such as gender, school type, household education and income level, and COVID-19 vaccination were significantly associated with reporting anxiety symptoms.
CHILD AND ADOLESCENT PSYCHIATRY AND MENTAL HEALTH
(2023)
Article
Pediatrics
Oliver Weinheimer, Philip Konietzke, Willi L. Wagner, Dorothea Weber, Beverly Newman, Craig J. Galban, Hans-Ulrich Kauczor, Marcus A. Mall, Terry E. Robinson, Mark O. Wielpuetz
Summary: This study aimed to quantify airway dimensions and air trapping on chest CT scans of school-age children with mild CF-lung disease over two years, and found that there were regional interdependencies between wall thickening and air trapping, as well as short-term regional interdependencies between air trapping and an increase in bronchiectasis.
FRONTIERS IN PEDIATRICS
(2023)
Article
Cell Biology
Marija Gredic, Vinita Sharma, Stefan Hadzic, Cheng-Yu Wu, Oleg Pak, Baktybek Kojonazarov, Julia Duerr, Marcus A. A. Mall, Andreas Guenther, Ralph T. T. Schermuly, Friedrich Grimminger, Werner Seeger, Simone Kraut, Natascha Sommer, Norbert Weissmann
Summary: This study aimed to investigate the effect of iNOS gene deletion on elastase-induced emphysema in mice. The results showed that iNOS gene deletion did not produce significant therapeutic effects on elastase-induced lung emphysema and pulmonary hypertension. Therefore, this study suggests that iNOS expression in pulmonary vascular or stromal cells might play a critical role in lung regeneration in emphysema.
Article
Medicine, General & Internal
Eva Steinke, Olaf Sommerburg, Simon Y. Graeber, Cornelia Joachim, Christiane Labitzke, Gyde Nissen, Isabell Ricklefs, Isa Rudolf, Matthias V. Kopp, Anna-Maria Dittrich, Marcus A. Mall, Mirjam Stahl
Summary: This study is a prospective, longitudinal cohort study aimed at determining influencing factors of early cystic fibrosis (CF) lung disease through the combined analysis of clinical information and biomaterials. The primary endpoints are the lung clearance index and magnetic resonance imaging scores, while secondary endpoints include pulmonary exacerbations, infection with pro-inflammatory pathogens, and anthropometric data.
FRONTIERS IN MEDICINE
(2023)
Article
Respiratory System
Patricia Leutz-Schmidt, Daiva-Elzbieta Optazaite, Olaf Sommerburg, Monika Eichinger, Sabine Wege, Eva Steinke, Simon Y. Graeber, Michael U. Puderbach, Jens-Peter Schenk, Abdulsattar Alrajab, Simon M. F. Triphan, Hans-Ulrich Kauczor, Mirjam Stahl, Marcus A. Mall, Mark O. Wielputz
Summary: This study evaluated the occurrence of bronchial artery dilatation (BAD) in patients with cystic fibrosis (CF) and its association with disease severity using magnetic resonance imaging (MRI). The results showed that the onset of BAD was associated with disease severity, lung function, and chronic Pseudomonas aeruginosa infection. This finding is important for assessing the severity of CF.
Article
Critical Care Medicine
Jennifer L. Goralski, Jordana E. Hoppe, Marcus A. Mall, Susanna A. McColley, Edward McKone, Bonnie Ramsey, Jonathan H. Rayment, Phil Robinson, Florian Stehling, Jennifer L. Taylor-Cousar, Elizabeth Tullis, Neil Ahluwalia, Anna Chin, Chenghao Chu, Mengdi Lu, Tao Niu, Tanya Weinstock, Felix Ratjen, Margaret Rosenfeld
Summary: This study evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of Elexacaftor/tezacaftor/ivacaftor in children aged 2-5 years. The results showed that the treatment was generally safe and well-tolerated in this age group and led to reductions in sweat chloride concentration and lung clearance index.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Article
Respiratory System
Annalisa Addante, Wilfred Raymond, Irina Gitlin, Annabelle Charbit, Xavier Orain, Aaron Wolfe Scheffler, Aditi Kuppe, Julia Duerr, Maria Daniltchenko, Marika Drescher, Simon Y. Graeber, Anne -Marie Healy, Stefan Oscarson, John V. Fahy, Marcus A. Mall
Summary: A novel carbohydrate compound, MUC-031, has been found to effectively cleave disulfide bonds in mucus, reducing mucus formation in patients with cystic fibrosis and muco-obstructive lung diseases. It has shown promising results in mice, improving airway mucus plugging, inflammation, and survival.
EUROPEAN RESPIRATORY JOURNAL
(2023)
Letter
Pediatrics
Ruth M. Urbantat, Charlotte O. Pioch, Niklas Ziegahn, Miriam S. Stegemann, Mirjam Stahl, Marcus A. Mall, Jobst F. Roehmel
PEDIATRIC PULMONOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Vladimir G. Magalhaes, Soeren Lukassen, Maike Drechsler, Jennifer Loske, Sandy S. Burkart, Sandra Wuest, Eva-Maria Jacobsen, Jobst Roehmel, Marcus A. Mall, Klaus-Michael Debatin, Roland Eils, Stella Autenrieth, Ales Janda, Irina Lehmann, Marco Binder
Summary: Children have a stronger innate immune response and enhanced cytokine-mediated interactions with epithelial cells, which may explain their remarkable resistance to COVID-19.
Article
Medicine, General & Internal
Simon Y. Graeber, Marcus A. Mall
Summary: Cystic fibrosis has become a leading candidate for transformative molecular therapy, with the breakthrough in highly effective modulator therapy in 2019 providing unprecedented clinical benefits. This paper reviews the understanding of the molecular mechanisms underlying CFTR dysfunction in cystic fibrosis, the progress in pharmacological approaches to restore CFTR function, and the potential of genetic therapies and gene editing approaches to cure cystic fibrosis.
Article
Respiratory System
Lena Wucherpfennig, Simon M. F. Triphan, Sabine Wege, Hans-Ulrich Kauczor, Claus P. Heussel, Olaf Sommerburg, Mirjam Stahl, Marcus A. Mall, Monika Eichinger, Mark O. Wielpuetz
Summary: This study found that bronchial artery dilatation (BAD) may be partially reversible under elexacaftor/tezacaftor/ivacaftor therapy in adult patients with cystic fibrosis (CF) who have established disease.
ANNALS OF THE AMERICAN THORACIC SOCIETY
(2023)