20 results on '"Behr, Jürgen"'
Search Results
2. High-resolution CT phenotypes in pulmonary sarcoidosis: a multinational Delphi consensus study
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Anderson, Adam, Morgenthau, Adam, Gaser, Adrian, Vizel, Alexander, Speranskaya, Alexandra, Gerke, Alicia, Goksel, Altinisik, Undurraga, Alvaro, Sharma, Amita, Oh, Andrea, Leung, Ann, Larici, Anna Rita, Prasse, Antje, Mazzei, Antonietta, Morais, Antonio, Bhalla, Ashu, Del Rio, Belen, Jankharia, Bhavin, Elicker, Brett, Pereira, Carlos, Biegelman-Aubry, Catherine, White, Charles, Ravaglia, Claudia, Hsia, Connie, Schaefer-Prokop, Cornelia, Launay, David, Talwar, Deepak, Castillo, Diego, Patel, Divya, Israel-Biet, Dominique, Valeyre, Dominique, Britt, Edward James, Bargagli, Elena, Bendstrup, Elisabeth, Crouser, Elliott, Nossent, Esther, Shmelev, Eugeny, Porquera, Eva Carmona, Bonella, Francesco, Cohen-Aubart, Fleur, Jeny, Florence, Ferrara, Giovanni, Jin, Gong Yong, Robbie, Hasti, Prosch, Helmut, Sumikawa, Hiromitsu, Ling-Pei, Ho, Lee, Ho Yun, Strambu, Irina, Buendia-Roldan, Ivette, Grutters, Jan, Ryu, Jay, Swigris, Jeff, Miedema, Jelle, Goo, Jin Mo, Barnett, Joseph, Verschakelen, Johny, Goldin, Jonathan, Seo, Joon Beom, Enghelmayer, Juan, Mana, Juan, Behr, Juergen, Patterson, Karen, Antoniou, Katerina, Brown, Kevin, Fujimoto, Kiminori, Savale, Laurent, Maier, Lisa, Richeldi, Luca, Neto, Manuel Lessa Ribeiro, Humbert, Marc, Judson, Marc, Veltkamp, Marcel, Wilsher, Margaret, Molina, Maria, Otaola, Maria, Revel, Marie-Pierre, Silva, Mario, Drent, Marjolein, Schiebler, Mark, Wijsenbeek-Lourens, Marlies, Bonifazi, Martina, Remy-Jardin, Martine, Koslow, Matthew, Balter, Meyer, Kreuter, Michael, Thillai, Muhunthan, Hamzeh, Nabeel, Chaudhuri, Nazia, Mogulkoc, Nesrin, Todd, Nevins, Screaton, Nick, Goh, Nicole, Shah, Nirav, Obi, Ogugua, Shlobin, Oksana, Baranova, Olga, Bresser, Paul, Rottoli, Paula, Brillet, Pierre-Yves, Said-Hartley, Qonita, Borie, Raphael, Mostard, Remy, van Zyl-smit, Richard, Kairalla, Ronaldo, Egashira, Ryoko, Boussouar, Samia, Lee, Sang Min, Bhalla, Sanjeev, Tomassetti, Sara, Quadrelli, Silvia, Hart, Simon P, Danoff, Sonye, Rajan, Sujeet, Choi, Sun Mi, Copley, Susan, Kim, Tae Jung, Johkoh, Takeshi, Corte, Tamera, McLoud, Theresa, Wessendorf, Thomas, Alfaro, Tiago, Arai, Toru, Costabel, Ulrich, Vicens-Zygmunt, Vanesa, Poletti, Venerino, Cottin, Vincent, Vucinic, Violeta, Wuyts, Wim, van Es, Wouter, Jeong, Yeon Joo, Inoue, Yoshikazu, Desai, Sujal R, Sivarasan, Nishanth, Johannson, Kerri A, George, Peter M, Culver, Daniel A, Devaraj, Anand, Lynch, David A, Milne, David, Renzoni, Elisabetta, Nunes, Hilario, Sverzellati, Nicola, Spagnolo, Paolo, Baughman, Robert P, Yadav, Ruchi, Piciucchi, Sara, Walsh, Simon L F, Kouranos, Vasileios, and Wells, Athol U
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- 2024
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3. Benralizumab Reduces Respiratory Exacerbations and Oral Glucocorticosteroid Dose in Patients with Severe Asthma and Eosinophilic Granulomatosis with Polyangiitis
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Mümmler, Carlo, primary, Mertsch, Pontus, additional, Barnikel, Michaela, additional, Haubner, Frank, additional, Schönermarck, Ulf, additional, Grabmaier, Ulrich, additional, Schulze-Koops, Hendrik, additional, Behr, Jürgen, additional, Kneidinger, Nikolaus, additional, and Milger, Katrin, additional
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- 2024
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4. Topotecan in a Real-World Small-Cell Lung Cancer Cohort: Prognostic Biomarkers Improve Selection of Patients for Second-Line Treatment.
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Lambrecht, Laura, Arnold, Paola, Behr, Jürgen, Mertsch, Pontus, Tufman, Amanda, and Kauffmann-Guerrero, Diego
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PATIENT selection ,PROGNOSIS ,OVERALL survival ,GLASGOW Coma Scale ,UNIVARIATE analysis - Abstract
Background: Small-cell lung cancer (SCLC) is a highly aggressive tumor, and overall survival (OS) remains poor despite intensive efforts to develop new treatment strategies. In second line, topotecan is the only approved drug, with a median OS of 5.9 months. However, real-world SCLC patients are often in worse condition and harbor more comorbidities than study populations. Therefore, the real-world performance of topotecan may differ from that seen in studies. Here, we analyzed outcomes of SCLC patients receiving topotecan and identified predictive and prognostic markers. Patients and Methods: We retrospectively analyzed 44 consecutive SCLC patients receiving topotecan between 2015 and 2022. We analyzed baseline characteristics (age, ECOG-PS, topotecan cycles, and dosage) and pre-treatment blood values (LDH, CRP, sodium) as well as prognostic scores (neutrophil/lymphocyte ratio (NLR), thrombocyte/lymphocyte ratio (TLR), Glasgow Prognostic Score, prognostic nutritional score, systemic inflammation index (SII), and the prognostic index) extracted from electronic patients' charts to identify predictive and prognostic markers. Results: In our cohort, mPFS and mOS were only 1.9 and 5.6 months, respectively. Gender, ECOG-PS, active brain metastases, NLR, GPS, PNI, and SII significantly influenced PFS and OS in univariate analysis. ECOG-PS (p > 0.001), active brain metastases (p = 0.001), and SII (p = 0.008) were significant independent prognostic variables in a multivariate COX regression model. Selecting patients by these three markers achieved an mPFS of 5.7 months and thus increased the mPFS three-fold. Patients not meeting all criteria had an mPFS of 1.8 months (p = 0.006). Patients identified by prognostic markers had an mOS of 9.1 months (p = 0.002). Conclusions: The efficacy of topotecan in SCLC real-world patients is poor, indicating that many patients were treated without any benefit. Easy-to-obtain markers can predict response and treatment efficacy and should therefore be validated in larger cohorts to identify patients who are more likely to benefit from topotecan. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Expiratory Venous Volume and Arterial Tortuosity are Associated with Disease Severity and Mortality Risk in Patients with COPD: Results from COSYCONET.
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Stoleriu, Mircea Gabriel, Pienn, Michael, Joerres, Rudolf A, Alter, Peter, Fero, Tamas, Urschler, Martin, Kovacs, Gabor, Olschewski, Horst, Kauczor, Hans-Ulrich, Wielpütz, Mark, Jobst, Bertram, Welte, Tobias, Behr, Jürgen, Trudzinski, Franziska C, Bals, Robert, Watz, Henrik, Vogelmeier, Claus F, Biederer, Jürgen, and Kahnert, Kathrin
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- 2024
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6. Stimuli-Specific Senescence of Primary Human Lung Fibroblasts Modulates Alveolar Stem Cell Function.
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Melo-Narváez, Maria Camila, Bramey, Nora, See, Fenja, Heinzelmann, Katharina, Ballester, Beatriz, Steinchen, Carina, Jain, Eshita, Federl, Kathrin, Hu, Qianjiang, Dhakad, Deepesh, Behr, Jürgen, Eickelberg, Oliver, Yildirim, Ali Önder, Königshoff, Melanie, and Lehmann, Mareike
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IDIOPATHIC pulmonary fibrosis ,CHRONIC obstructive pulmonary disease ,PROGENITOR cells ,LUNG diseases ,CELL physiology - Abstract
Aging is the main risk factor for chronic lung diseases (CLDs) including idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Accordingly, hallmarks of aging like cellular senescence are increased in these patients in different lung cell types including fibroblasts. However, little is known about the different triggers that induce a senescence phenotype in different disease backgrounds and its role in CLD pathogenesis. Therefore, we characterized senescence in primary human lung fibroblasts (phLF) from control, IPF, or COPD patients at baseline and after exposure to disease-relevant insults (H
2 O2 , bleomycin, TGF-β1) and studied their capacity to support progenitor cell potential in a lung organoid model. Bulk-RNA sequencing revealed that phLF from IPF and COPD activate different transcriptional programs but share a similar senescence phenotype at baseline. Moreover, H2 O2 and bleomycin but not TGF-β1 induced senescence in phLF from different disease origins. Exposure to different triggers resulted in distinct senescence programs in phLF characterized by different SASP profiles. Finally, co-culture with bleomycin- and H2 O2 -treated phLF reduced the progenitor cell potential of alveolar epithelial progenitor cells. In conclusion, phLF from COPD and IPF share a conserved senescence response that varies depending on the insult and impairs alveolar epithelial progenitor capacity ex vivo. [ABSTRACT FROM AUTHOR]- Published
- 2024
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7. Meaningful Endpoints for Idiopathic Pulmonary Fibrosis (IPF) Clinical Trials: Emphasis on ‘Feels, Functions, Survives’. Report of a Collaborative Discussion in a Symposium with Direct Engagement from Representatives of Patients, Investigators, the National Institutes of Health, a Patient Advocacy Organization, and a Regulatory Agency
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Raghu, Ganesh, primary, Ghazipura, Marya, additional, Fleming, Thomas R., additional, Aronson, Kerri I., additional, Behr, Jürgen, additional, Brown, Kevin K., additional, Flaherty, Kevin R., additional, Kazerooni, Ella A., additional, Maher, Toby M., additional, Richeldi, Luca, additional, Lasky, Joseph A., additional, Swigris, Jeffrey J., additional, Busch, Robert, additional, Garrard, Lili, additional, Ahn, Dong-Hyun, additional, Li, Ji, additional, Puthawala, Khalid, additional, Rodal, Gabriela, additional, Seymour, Sally, additional, Weir, Nargues, additional, Danoff, Sonye K., additional, Ettinger, Neil, additional, Goldin, Jonathan, additional, Glassberg, Marilyn K., additional, Kawano-Dourado, Leticia, additional, Khalil, Nasreen, additional, Lancaster, Lisa, additional, Lynch, David A., additional, Mageto, Yolanda, additional, Noth, Imre, additional, Shore, Jessica E., additional, Wijsenbeek, Marlies, additional, Brown, Robert, additional, Grogan, Daniel, additional, Ivey, Dorothy, additional, Golinska, Patrycja, additional, Karimi-Shah, Banu, additional, and Martinez, Fernando J., additional
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- 2024
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8. Disease trajectories in interstitial lung diseases – data from the EXCITING-ILD registry
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Buschulte, Katharina, primary, Kabitz, Hans-Joachim, additional, Hagmeyer, Lars, additional, Hammerl, Peter, additional, Esselmann, Albert, additional, Wiederhold, Conrad, additional, Skowasch, Dirk, additional, Stolpe, Christoph, additional, Joest, Marcus, additional, Veitshans, Stefan, additional, Höffgen, Marc, additional, Maqhuzu, Phillen, additional, Schwarzkopf, Larissa, additional, Hellmann, Andreas, additional, Pfeifer, Michael, additional, Behr, Jürgen, additional, Karpavicius, Rainer, additional, Günther, Andreas, additional, Polke, Markus, additional, Höger, Philipp, additional, Somogyi, Vivien, additional, Lederer, Christoph, additional, Markart, Philipp, additional, and Kreuter, Michael, additional
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- 2024
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9. Effects of triple therapy on disease burden in patients of GOLD groups C and D: results from the observational COPD cohort COSYCONET
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Zader, Jennifer A., primary, Jörres, Rudolf A., additional, Mayer, Imke, additional, Alter, Peter, additional, Bals, Robert, additional, Watz, Henrik, additional, Mertsch, Pontus, additional, Rabe, Klaus F., additional, Herth, Felix, additional, Trudzinski, Franziska C., additional, Welte, Tobias, additional, Kauczor, Hans-Ulrich, additional, Behr, Jürgen, additional, Walter, Julia, additional, Vogelmeier, Claus F., additional, and Kahnert, Kathrin, additional
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- 2024
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10. Zinpentraxin Alfa for Idiopathic Pulmonary Fibrosis: The Randomized Phase III STARSCAPE Trial
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Richeldi, Luca, primary, Schiffman, Courtney, additional, Behr, Jürgen, additional, Inoue, Yoshikazu, additional, Corte, Tamera J, additional, Cottin, Vincent, additional, Jenkins, R. Gisli, additional, Nathan, Steven D, additional, Raghu, Ganesh, additional, Walsh, Simon L. F., additional, Jayia, Parminderjit K., additional, Kamath, Nikhil, additional, and Martinez, Fernando J., additional
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- 2024
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11. Hospitalisation patterns in interstitial lung diseases: data from the EXCITING-ILD registry
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Buschulte, Katharina, primary, Kabitz, Hans-Joachim, additional, Hagmeyer, Lars, additional, Hammerl, Peter, additional, Esselmann, Albert, additional, Wiederhold, Conrad, additional, Skowasch, Dirk, additional, Stolpe, Christoph, additional, Joest, Marcus, additional, Veitshans, Stefan, additional, Höffgen, Marc, additional, Maqhuzu, Phillen, additional, Schwarzkopf, Larissa, additional, Hellmann, Andreas, additional, Pfeifer, Michael, additional, Behr, Jürgen, additional, Karpavicius, Rainer, additional, Günther, Andreas, additional, Polke, Markus, additional, Höger, Philipp, additional, Somogyi, Vivien, additional, Lederer, Christoph, additional, Markart, Philipp, additional, and Kreuter, Michael, additional
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- 2024
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12. Multicenter Standardization of Phase‐Resolved Functional Lung MRI in Patients With Suspected Chronic Thromboembolic Pulmonary Hypertension.
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Moher Alsady, Tawfik, Voskrebenzev, Andreas, Behrendt, Lea, Olsson, Karen, Heußel, Claus Peter, Gruenig, Ekkehard, Gall, Henning, Ghofrani, Ardeschir, Roller, Fritz, Harth, Sebastian, Marshall, Helen, Hughes, Paul J.C., Wild, Jim, Swift, Andrew J., Kiely, David G., Behr, Jürgen, Dinkel, Julien, Beitzke, Dietrich, Lang, Irene M., and Schmidt, Kai Helge
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FUNCTIONAL magnetic resonance imaging ,PULMONARY hypertension ,MAGNETIC resonance imaging ,PEARSON correlation (Statistics) ,CONTRAST-enhanced magnetic resonance imaging - Abstract
Background: Detection of pulmonary perfusion defects is the recommended approach for diagnosing chronic thromboembolic pulmonary hypertension (CTEPH). This is currently achieved in a clinical setting using scintigraphy. Phase‐resolved functional lung (PREFUL) magnetic resonance imaging (MRI) is an alternative technique for evaluating regional ventilation and perfusion without the use of ionizing radiation or contrast media. Purpose: To assess the feasibility and image quality of PREFUL‐MRI in a multicenter setting in suspected CTEPH. Study Type: This is a prospective cohort sub‐study. Population: Forty‐five patients (64 ± 16 years old) with suspected CTEPH from nine study centers. Field Strength/Sequence: 1.5 T and 3 T/2D spoiled gradient echo/bSSFP/T2 HASTE/3D MR angiography (TWIST). Assessment: Lung signal‐to‐noise ratio (SNR) and contrast‐to‐noise ratio (CNR) were compared between study centers with different MRI machines. The contrast between normally and poorly perfused lung areas was examined on PREFUL images. The perfusion defect percentage calculated using PREFUL‐MRI (QDPPREFUL) was compared to QDP from the established dynamic contrast‐enhanced MRI technique (QDPDCE). Furthermore, QDPPREFUL was compared between a patient subgroup with confirmed CTEPH or chronic thromboembolic disease (CTED) to other clinical subgroups. Statistical Tests: t‐Test, one‐way analysis of variance (ANOVA), Pearson's correlation. Significance level was 5%. Results: Significant differences in lung SNR and CNR were present between study centers. However, PREFUL perfusion images showed a significant contrast between normally and poorly perfused lung areas (mean delta of normalized perfusion −4.2% SD 3.3) with no differences between study sites (ANOVA: P = 0.065). QDPPREFUL was significantly correlated with QDPDCE (r = 0.66), and was significantly higher in 18 patients with confirmed CTEPH or CTED (57.9 ± 12.2%) compared to subgroups with other causes of PH or with excluded PH (in total 27 patients with mean ± SD QDPPREFUL = 33.9 ± 17.2%). Data Conclusion: PREFUL‐MRI could be considered as a non‐invasive method for imaging regional lung perfusion in multicenter studies. Level of Evidence: 3 Technical Efficacy: Stage 1 [ABSTRACT FROM AUTHOR]
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- 2024
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13. Long-term multicenter comparison shows equivalent efficacy of monoclonal antibodies in severe asthma therapy.
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Kayser, Moritz Z., Suhling, Hendrik, Fuge, Jan, Hinze, Christopher A., Drick, Nora, Kneidinger, Nikolaus, Behr, Jürgen, Taube, Christian, Welte, Tobias, Haasler, Ina, and Milger, Katrin
- Abstract
Background: Monoclonal antibodies (biologics) drastically changed severe asthma therapy. Mepolizumab (anti-interleukin (IL) 5), benralizumab (anti-IL5 receptor alpha), and dupilumab (anti-IL4/13) are the most used biologics in this context. While all biologics are efficient individually, the choice of biologic is complicated by insufficient data on their comparative long-term treatment efficacy. Here, we compare the real-life efficacy of these biologics in asthma therapy over 12 months. Methods: 280 severe asthma patients treated with mepolizumab (129/280, 46%), benralizumab (83/280, 30%) or dupilumab (68/280, 24%) for one year were analyzed retrospectively. Data were collected at baseline and after 6 and 12 months of therapy. Endpoints were changes pulmonary function (PF), exacerbation rate, oral corticosteroid (OCS) use and dose, asthma control test (ACT) score and fractional exhaled nitric oxide (FeNO) levels as well as responder status measured by the recently published "Biologic Asthma Response Score" (BARS). Results: All biologics led to significant improvements in PF, ACT and OCS dose. Only Mepolizumab and Benralizumab significantly decreased the exacerbation rate, while only Mepolizumab and Dupilumab significantly decreased FeNO. Responder rates measured by BARS were high across all groups: roughly half of all patients achieved full response and most of the remainder achieved at least partial responder status. Overall, outcomes were similar between groups after both 6 and 12 months. Conclusions: All biologics showed great efficacy in individual parameters and high responder rates measured by BARS without a clinically relevant advantage for any antibody. Response was usually achieved after 6 months and retained at 12 months, emphasizing the utility of early response assessment. [ABSTRACT FROM AUTHOR]
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- 2024
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14. Simultaneous Occurrence of HER2Mutations in EGFRMutant NSCLC: Case Reports
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Resuli, Blerina, Kauffmann-Guerrero, Diego, Behr, Jürgen, and Tufman, Amanda
- Abstract
HER2mutation and amplification have been identified as distinct molecular targets in lung cancer with different therapeutic and prognostic values. The coexistence of HER2and EGFRmutations is extremely rare, and therefore, no data exist on the best treatment in these cases (Nagasaka et al., 2022).
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- 2024
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15. Quantitative Proteomics for the Comprehensive Analysis of Stress Responses of Lactobacillus paracaseisubsp. paracaseiF19
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Schott, Ann-Sophie, Behr, Jürgen, Geißler, Andreas J., Kuster, Bernhard, Hahne, Hannes, and Vogel, Rudi F.
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Lactic acid bacteria are broadly employed as starter cultures in the manufacture of foods. Upon technological preparation, they are confronted with drying stress that amalgamates numerous stress conditions resulting in losses of fitness and survival. To better understand and differentiate physiological stress responses, discover general and specific markers for the investigated stress conditions, and predict optimal preconditioning for starter cultures, we performed a comprehensive genomic and quantitative proteomic analysis of a commonly used model system, Lactobacillus paracaseisubsp. paracaseiTMW 1.1434 (isogenic with F19) under 11 typical stress conditions, including among others oxidative, osmotic, pH, and pressure stress. We identified and quantified >1900 proteins in triplicate analyses, representing 65% of all genes encoded in the genome. The identified genes were thoroughly annotated in terms of subcellular localization prediction and biological functions, suggesting unbiased and comprehensive proteome coverage. In total, 427 proteins were significantly differentially expressed in at least one condition. Most notably, our analysis suggests that optimal preconditioning toward drying was predicted to be alkaline and high-pressure stress preconditioning. Taken together, we believe the presented strategy may serve as a prototypic example for the analysis and utility of employing quantitative-mass-spectrometry-based proteomics to study bacterial physiology.
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- 2024
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16. [Diagnosis and Treatment of Hypersensitivity Pneumonitis - S2k Guideline of the German Respiratory Society and the German Society for Allergology and Clinical Immunology].
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Koschel D, Behr J, Berger M, Bonella F, Hamer O, Joest M, Jonigk D, Kreuter M, Leuschner G, Nowak D, Raulf M, Rehbock B, Schreiber J, Sitter H, Theegarten D, and Costabel U
- Abstract
Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease (ILD) in sensitized individuals caused by a large variety of inhaled antigens. The clinical form of acute HP is often misdiagnosed, while the chronic form, especially the chronic fibrotic HP, is difficult to differentiate from other fibrotic ILDs. The present guideline for the diagnosis and treatment of HP replaces the former German recommendations for the diagnosis of HP from 2007 and is amended explicitly by the issue of the chronic fibrotic form, as well as by treatment recommendations for the first time. The evidence was discussed by a multidisciplinary committee of experts. Then, recommendations were formulated for twelve questions on important issues of diagnosis and treatment strategies. Recently published national and international guidelines for ILDs and HP were considered. Detailed background information on HP is useful for a deeper insight into HP and the handling of the guideline., Competing Interests: Eine Übersicht der Interessenkonflikte findet sich im Internet unter http://awmf.org; AWMF-Registriernummer 020-036., (Thieme. All rights reserved.)
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- 2024
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17. Midregional Proatrial Natriuretic Peptide (MRproANP) is associated with vertebral fractures and low bone density in patients with chronic obstructive pulmonary disease (COPD).
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Trudzinski FC, Jörres RA, Alter P, Watz H, Vogelmeier CF, Kauczor HU, Thangamani S, Debic M, Welte T, Behr J, Kahnert K, Bals R, Herr C, Heußel CP, Biederer J, von Stackelberg O, Fähndrich S, Wouters EFM, Waschki B, Rabe KF, Herth FJF, and Palm V
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- Aged, Female, Humans, Male, Middle Aged, Cohort Studies, Osteoporotic Fractures blood, Osteoporotic Fractures epidemiology, Osteoporotic Fractures diagnosis, Osteoporotic Fractures diagnostic imaging, Protein Precursors blood, Atrial Natriuretic Factor blood, Biomarkers blood, Bone Density physiology, Pulmonary Disease, Chronic Obstructive blood, Pulmonary Disease, Chronic Obstructive epidemiology, Pulmonary Disease, Chronic Obstructive diagnosis, Spinal Fractures blood, Spinal Fractures epidemiology, Spinal Fractures diagnostic imaging
- Abstract
Background: Patients with COPD are often affected by loss of bone mineral density (BMD) and osteoporotic fractures. Natriuretic peptides (NP) are known as cardiac markers, but have also been linked to fragility-associated fractures in the elderly. As their functions include regulation of fluid and mineral balance, they also might affect bone metabolism, particularly in systemic disorders such as COPD., Research Question: We investigated the association between NP serum levels, vertebral fractures and BMD assessed by chest computed tomography (CT) in patients with COPD., Methods: Participants of the COSYCONET cohort with CT scans were included. Mean vertebral bone density on CT (BMD-CT) as a risk factor for osteoporosis was assessed at the level of TH12 (AI-Rad Companion), and vertebral compression fractures were visually quantified by two readers. Their relationship with N-terminal pro-B-type natriuretic peptide (NT-proBNP), Mid-regional pro-atrial natriuretic peptide (MRproANP) and Midregional pro-adrenomedullin (MRproADM) was determined using group comparisons and multivariable analyses., Results: Among 418 participants (58% male, median age 64 years, FEV
1 59.6% predicted), vertebral fractures in TH12 were found in 76 patients (18.1%). Compared to patients without fractures, these had elevated serum levels (p ≤ 0.005) of MRproANP and MRproADM. Using optimal cut-off values in multiple logistic regression analyses, MRproANP levels ≥ 65 nmol/l (OR 2.34; p = 0.011) and age (p = 0.009) were the only significant predictors of fractures after adjustment for sex, BMI, smoking status, FEV1 % predicted, SGRQ Activity score, daily physical activity, oral corticosteroids, the diagnosis of cardiac disease, and renal impairment. Correspondingly, MRproANP (p < 0.001), age (p = 0.055), SGRQ Activity score (p = 0.061) and active smoking (p = 0.025) were associated with TH12 vertebral density., Interpretation: MRproANP was a marker for osteoporotic vertebral fractures in our COPD patients from the COSYCONET cohort. Its association with reduced vertebral BMD on CT and its known modulating effects on fluid and ion balance are suggestive of direct effects on bone mineralization., Trial Registration: ClinicalTrials.gov NCT01245933, Date of registration: 18 November 2010., (© 2024. The Author(s).)- Published
- 2024
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18. Clinicopathological characterization of next-generation sequencing detected mutations in lung cancers-a single-center experience.
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Walter J, Tufman A, Kumbrink J, Neumann J, Kahnert K, Sellmer L, Jung A, Behr J, and Kauffmann-Guerrero D
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Background: Despite many advances in molecular procedures many lung cancer patients do not receive full panel testing. This can limit the comprehensive understanding of their disease and potentially hinder personalized treatment options., Methods: In this retrospective analysis, we used results from next-generation sequencing (NGS) testing of 154 patients with adenocarcinoma (AC) or squamous cell carcinoma (SCC) of the lung treated at the University Hospital, Ludwig-Maximilians Universität (LMU) Munich between 2018 and 2021. We compared different clinicopathological features and patients' baseline characteristics with results of NGS testing. We used t -test and analysis of variance (ANOVA) to compare metric- and χ
2 -test and Fisher's exact test to compare categorical variables., Results: NGS testing found mutations in 107 (69.5%) patients; 44 patients (28.6%) had more than one mutation. The majority (79.2%) of patients had AC and 64.9% were metastasized at diagnosis. Patients with detected mutations had significantly higher PD-L1 expression than those without mutations (36.4% vs. 19.2%, P=0.005). Mean PD-L1 expression also differed between different mutations ranging from 24.0% in EGFR to 56.8% in patients with MET alterations, and increased with the number of different mutations (P=0.07). EGFR mutations were significantly more common in females compared to males (22.9% vs. 9.5%, P=0.04) and PIK3CA mutations significantly more common in SCC (21.9% vs. 2.5%, P=0.004). We found 23 different mutations in AC and 13 different gene mutations in SCC., Conclusions: Mutation profiles differed by histological type and metastases status and were significantly associated with PD-L1 expression. In the context of limited resources, our results may help prioritize patient for testing when tissue material and funding is limited., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-23-751/coif). The authors have no conflicts of interest to declare., (2024 Translational Lung Cancer Research. All rights reserved.)- Published
- 2024
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19. Treatment strategies and survival of patients with connective tissue disease and pulmonary arterial hypertension: a COMPERA analysis.
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Distler O, Ofner C, Huscher D, Jordan S, Ulrich S, Stähler G, Grünig E, Held M, Ghofrani HA, Claussen M, Lange TJ, Klose H, Rosenkranz S, Vonk-Noordegraaf A, Vizza CD, Delcroix M, Opitz C, Pausch C, Scelsi L, Neurohr C, Olsson KM, Coghlan JG, Halank M, Skowasch D, Behr J, Milger K, Remppis BA, Skride A, Jureviciene E, Gumbiene L, Miliauskas S, Löffler-Ragg J, Wilkens H, Pittrow D, Hoeper MM, and Ewert R
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- Humans, Familial Primary Pulmonary Hypertension complications, Pulmonary Arterial Hypertension etiology, Pulmonary Arterial Hypertension complications, Mixed Connective Tissue Disease complications, Mixed Connective Tissue Disease drug therapy, Connective Tissue Diseases complications, Connective Tissue Diseases drug therapy, Connective Tissue Diseases diagnosis, Hypertension, Pulmonary drug therapy, Hypertension, Pulmonary etiology, Lupus Erythematosus, Systemic complications, Lupus Erythematosus, Systemic drug therapy, Scleroderma, Systemic complications
- Abstract
Objectives: Pulmonary arterial hypertension (PAH) occurs in various connective tissue diseases (CTDs). We sought to assess contemporary treatment patterns and survival of patients with various forms of CTD-PAH., Methods: We analysed data from COMPERA, a European pulmonary hypertension registry, to describe treatment strategies and survival in patients with newly diagnosed PAH associated with SSc, SLE, MCTD, UCTD and other types of CTD. All-cause mortality was analysed according to the underlying CTD. For patients with SSc-PAH, we also assessed survival according to initial therapy with endothelin receptor antagonists (ERAs), phosphodiesterase type 5 inhibitors (PDE5is) or a combination of these two drug classes., Results: This analysis included 607 patients with CTD-PAH. Survival estimates at 1, 3 and 5 years for SSc-PAH (n = 390) were 85%, 59% and 42%; for SLE-PAH (n = 34) they were 97%, 77% and 61%; for MCTD-PAH (n = 33) they were 97%, 70% and 59%; for UCTD-PAH (n = 60) they were 88%, 67% and 52%; and for other CTD-PAH (n = 90) they were 92%, 69% and 55%, respectively. After multivariable adjustment, the survival of patients with SSc-PAH was significantly worse compared with the other conditions (P = 0.001). In these patients, the survival estimates were significantly better with initial ERA-PDE5i combination therapy than with initial ERA or PDE5i monotherapy (P = 0.016 and P = 0.012, respectively)., Conclusions: Mortality remains high in patients with CTD-PAH, especially for patients with SSc-PAH. However, for patients with SSc-PAH, our results suggest that long-term survival may be improved with initial ERA-PDE5i combination therapy compared with initial monotherapy., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
- Published
- 2024
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20. Sfrp1 inhibits lung fibroblast invasion during transition to injury induced myofibroblasts.
- Author
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Mayr CH, Sengupta A, Asgharpour S, Ansari M, Pestoni JC, Ogar P, Angelidis I, Liontos A, Rodriguez-Castillo JA, Lang NJ, Strunz M, Porras-Gonzalez D, Gerckens M, De Sadeleer LJ, Oehrle B, Viteri-Alvarez V, Fernandez IE, Tallquist M, Irmler M, Beckers J, Eickelberg O, Stoleriu GM, Behr J, Kneidinger N, Wuyts WA, Wasnick RM, Yildirim AÖ, Ahlbrecht K, Morty RE, Samakovlis C, Theis FJ, Burgstaller G, and Schiller HB
- Abstract
Background: Fibroblast to myofibroblast conversion is a major driver of tissue remodeling in organ fibrosis. Distinct lineages of fibroblasts support homeostatic tissue niche functions, yet, their specific activation states and phenotypic trajectories during injury and repair have remained unclear., Methods: We combined spatial transcriptomics, multiplexed immunostainings, longitudinal single-cell RNA-seq and genetic lineage tracing to study fibroblast fates during mouse lung regeneration. Our findings were validated in IPF patient tissues in situ as well as in cell differentiation and invasion assays using patient lung fibroblasts. Cell differentiation and invasion assays established a function of SFRP1 in regulating human lung fibroblast invasion in response to TGFβ1., Measurements and Main Results: We discovered a transitional fibroblast state characterized by high Sfrp1 expression, derived from both Tcf21 -Cre lineage positive and negative cells. Sfrp1 + cells appeared early after injury in peribronchiolar, adventitial and alveolar locations and preceded the emergence of myofibroblasts. We identified lineage specific paracrine signals and inferred converging transcriptional trajectories towards Sfrp1 + transitional fibroblasts and Cthrc1 + myofibroblasts. TGFβ1 downregulated SFRP1 in non-invasive transitional cells and induced their switch to an invasive CTHRC1+ myofibroblast identity. Finally, using loss of function studies we showed that SFRP1 modulates TGFβ1 induced fibroblast invasion and RHOA pathway activity., Conclusions: Our study reveals the convergence of spatially and transcriptionally distinct fibroblast lineages into transcriptionally uniform myofibroblasts and identifies SFRP1 as a modulator of TGFβ1 driven fibroblast phenotypes in fibrogenesis. These findings are relevant in the context of therapeutic interventions that aim at limiting or reversing fibroblast foci formation., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)
- Published
- 2024
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