Article
Biochemistry & Molecular Biology
Jan C. Kamp, Naomi N. Kappe, Carlos Fernandez Moro, Jan Fuge, Mark P. Kuehnel, Sabine Wrenger, Tobias Welte, Bart van Hoek, Danny D. Jonigk, Padmini P. S. J. Khedoe, Pavel Strnad, Mikael Bjornstedt, Jan Stolk, Sabina Janciauskiene, Antal Nemeth
Summary: PiZZ (Glu342Lys) alpha 1-antitrypsin deficiency (AATD) is a risk factor for liver disease development in children, characterized by intrahepatic AAT polymerization. The presence of Z-AAT polymers in hepatocytes is common among PiZZ children, but the clinical outcomes vary, with some developing neonatal cholestasis and cirrhosis. The expression of genes related to liver fibrosis/cirrhosis and lipid, aldehyde/ketone, and bile acid metabolism differ between groups, suggesting that changes in specific genes and pathways may reflect the degree of liver injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Juan Luis Rodriguez Hermosa, Gianna Vargas Centanaro, Maria Estela Gonzalez Castro, Marc Miravitlles, Lourdes Lazaro-Asegurado, Beatriz Maria Jimenez-Rodriguez, Rosanel Amaro Rodriguez, Rosaly Moreno Mendez, Maria Torres-Duran, Jose Maria Hernandez-Perez, Ana Maria Humanes-Navarro, Myriam Calle Rubio
Summary: This study found that patients with allelic variants of SERPINA1 gene, which is associated with severe cases of COVID-19, were more likely to have alpha-1 antitrypsin deficiency (AATD), making them more susceptible to severe COVID-19. Therefore, increased precautionary measures are recommended for AATD patients.
Article
Cell Biology
Adriana Ordonez, Heather P. Harding, Stefan J. Marciniak, David Ron
Summary: The study explored the cellular factors affecting the secretion of circulating polymers of alpha 1-antitrypsin, finding that cargo receptors LMAN1 and SURF4 are crucial for polymer secretion. Disruption of these receptors leads to a defect in alpha 1-antitrypsin secretion, particularly polymers, indicating their important role in regulating the process.
Article
Medicine, Research & Experimental
Maximilian Ebert, Uwe Jerke, Claudia Eulenberg-Gustavus, Lovis Kling, Dieter Jenne, Marieluise Kirchner, Philipp Mertins, Markus Bieringer, Saban Elitok, Kai-Uwe Eckardt, Adrian Schreiber, Alan D. Salama, Ralph Kettritz
Summary: The levels of PR3 and AAT were significantly increased in patients with both PR3-AAV and MPO-AAV, but only in PR3-AAV did the level of PR3 correlate with the ANCA titer, inflammatory response, and disease severity. Mechanistically, AAT prevented PR3 from binding to CD177, reducing the binding of PR3-ANCA to neutrophil surface antigens. Active patients with PR3-AAV showed methionine oxidation in plasma AAT, which was replicated by ANCA-activated neutrophils. The protective effects of PR3-related AAT were compromised by oxidation in the AAT reactive center loop, but preserved with valine and leucine substitution for critical methionines.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Immunology
Xiyuan Bai, An Bai, Michele Tomasicchio, James R. Hagman, Ashley M. Buckle, Arnav Gupta, Vineela Kadiyala, Shaun Bevers, Karina A. Serban, Kevin Kim, Zhihong Feng, Kathrin Spendier, Guy Hagen, Lorelenn Fornis, David E. Griffith, Monika Dzieciatkowska, Robert A. Sandhaus, Anthony N. Gerber, Edward D. Chan
Summary: This study identifies a new mechanism for the gene regulation, anti-inflammatory, and host-defense properties of AAT. AAT binds to the cytoplasmic glucocorticoid receptor (GR) in human macrophages, leading to inhibition of NF-kB activation and IL-8 production, as well as induction of angiopoietin-like 4 protein. This AAT-GR interaction contributes to a host-protective role against mycobacteria in macrophages.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Genetics & Heredity
Lela Lackey, Aaztli Coria, Auyon J. Ghosh, Phil Grayeski, Luke Hatfield, Vijay Shankar, John Platig, Zhonghui Xu, Silvia B. Ramos, Edwin K. Silverman, Victor E. Ortega, Michael H. Cho, Craig P. Hersh, Brian D. Hobbs, Peter Castaldi, Alain Laederach
Summary: The study identifies a novel alternative polyadenylation event that regulates A1AT protein expression in COPD, involving two polyadenylation sites in the SERPINA1 mRNA. Additionally, differences in SERPINA1 distal ratio distribution among cell types in the liver and lung were observed in single-cell RNA-seq analysis.
Article
Respiratory System
Sine V. Winther, Eskild M. Landt, Borge G. Nordestgaard, Niels Seersholm, Morten Dahl
Summary: Individuals with alpha(1)-antitrypsin deficiency have an increased risk of heart failure hospitalization and heart failure-specific mortality in the Danish population.
Review
Medicine, General & Internal
Andrea Vianello, Gabriella Guarnieri, Fausto Braccioni, Beatrice Molena, Sara Lococo, Alessia Achille, Federico Lionello, Leonardo Salviati, Marco Caminati, Gianenrico Senna
Summary: This review examines the correlation between alpha 1-antitrypsin deficiency, SARS-CoV-2 infection, and COVID-19 mortality rates, suggesting that ethnic differences in SERPINA1 allele frequencies may partially explain the geographic disparities. Shared pathogenetic pathways are also discussed as theoretical basis for the epidemiological findings, along with the potential use of AAT augmentation therapy in patients with COVID-19.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Biotechnology & Applied Microbiology
Jonathan B. Rosenberg, P. De Bishnu, Alessandria Greco, Nicholas Gorman, Vikrum Kooner, Alvin Chen, Melissa Yost-Bido, Carlos Munoz-Zuluaga, Stephen M. Kaminsky, Mahboubeh Rostami, Sebastien Monette, Ronald G. Crystal, Dolan Sondhi
Summary: Alpha 1-antitrypsin (AAT) deficiency is a common hereditary disorder with a risk of early-onset emphysema. AAT, produced in the liver, protects the lungs from protease damage, but deficiency leads to lung tissue destruction. Oxidative damage to AAT prevents it from inhibiting target proteases. In this study, the safety of intravenous administration of an engineered AAT variant, AAV8hAAT(AVL), was evaluated in mice. The study showed that AAV8hAAT(AVL) is safe with no significant adverse effects, demonstrating its potential for further clinical studies.
HUMAN GENE THERAPY
(2023)
Article
Hematology
Julie Riis, Borge G. Nordestgaard, Shoaib Afzal
Summary: The study revealed an association between the alpha(1)-antitrypsin Z genetic variant and an increased risk of venous thromboembolism, with hazard ratios of 2.2 for homozygotes and 1.1 for heterozygotes. The absolute risk of venous thromboembolism associated with alpha(1)-antitrypsin ZZ homozygosity was 7.8%.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Medicine, General & Internal
Chin-Ling Li, Hui-Chuan Chang, Ching-Wan Tseng, Yuh-Chyn Tsai, Jui-Fang Liu, Meng-Lin Tsai, Meng-Chih Lin, Shih-Feng Liu
Summary: The BODE and ADO indices were found to be correlated with hospitalization frequency and hospitalization days in COPD patients. However, the BODE index showed slightly better predictive accuracy than the ADO index in these aspects.
MEDICINA-LITHUANIA
(2023)
Article
Pathology
Josiah D. Murray, Maria A. Willrich, Michael J. Krowka, Aleh Bobr, David L. Murray, Kevin C. Halling, Rondell P. Graham, Melissa R. Snyder
Summary: The study evaluated the effectiveness of a LC-MSIMS-based algorithm in detecting AAT deficiency, showing high sensitivity and cost-effectiveness with a significant reduction in IEF testing. The algorithm demonstrated a 99.9% sensitivity for detecting deficiency-associated phenotypes and was particularly successful in identifying heterozygous patients with specific allele pairings.
AMERICAN JOURNAL OF CLINICAL PATHOLOGY
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Ju Gang Nam, Hye-Rin Kang, Sang Min Lee, Hyungjin Kim, Chanyoung Rhee, Jin Mo Goo, Yeon-Mok Oh, Chang-Hoon Lee, Chang Min Park
Summary: This study developed a deep learning-based survival prediction model for patients with chronic obstructive pulmonary disease (COPD) using chest radiographs and other clinical factors. The model showed superior performance in predicting 5-year survival compared to the traditional FEV1 index and demonstrated good calibration in multiple independent test cohorts. Additionally, the model achieved higher predictive accuracy compared to other clinical indexes.
Article
Medicine, General & Internal
Monica Pons, Alexa Nunez, Cristina Esquinas, Maria Torres-Duran, Juan Luis Rodriguez-Hermosa, Myriam Calle, Ramon Tubio-Perez, Irene Belmonte, Francisco Rodriguez-Frias, Esther Rodriguez, Joan Genesca, Marc Miravitlles, Miriam Barrecheguren
Summary: Transient elastography can help identify AATD patients with liver fibrosis, even if liver enzymes are normal. Patients with AATD frequently have abnormal liver enzymes, but most of them do not have significant liver fibrosis.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Respiratory System
Maria Torres-Duran, Jose Luis Lopez-Campos, Juan Luis Rodriguez-Hermosa, Cristina Esquinas, Cristina Martinez-Gonzalez, Jose Maria Hernandez-Perez, Carlota Rodriguez, Ana Bustamante, Francisco Casas-Maldonado, Miriam Barrecheguren, Cruz Gonzalez, Marc Miravitlles
Summary: There is a high prevalence of PI*SZ in Spain, and patients with this genotype tend to have less severe lung disease but a higher prevalence of asthma.
Article
Obstetrics & Gynecology
Patrick Rozenberg, Marie-Victoire Senat, Philippe Deruelle, Norbert Winer, Emmanuel Simon, Yves Ville, Gilles Kayem, Raphael Porcher, Elodie Perrodeau, Raoul Desbriere, Isabelle Boutron
Summary: This multicenter, randomized, controlled trial aimed to evaluate the impact of proposing mode of delivery based on ultrasound measurement of lower uterine segment thickness on maternal-fetal mortality and morbidity among pregnant women with previous cesarean delivery. The study results did not show a statistically significant difference in adverse outcomes between the study group and control group, indicating the need for further research due to low statistical power.
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
(2022)
Article
Respiratory System
Olivier Hermine, Xavier Mariette, Raphael Porcher, Matthieu Resche-Rigon, Pierre-Louis Tharaux, Philippe Ravaud
Summary: This study aimed to determine whether anti-interleukin (IL)-6 receptors improve outcomes in critically ill patients with COVID-19 pneumonia. The results showed that anti-IL-6 receptor treatment did not significantly increase the number of patients alive without the need for noninvasive ventilation (NIV) or mechanical ventilation (MV) by day 14.
EUROPEAN RESPIRATORY JOURNAL
(2022)
Letter
Respiratory System
Claudio Rabec, Emeline Fresnel, Yann Retory, Kaixian Zhu, Karima Joly, Adrien Kerfourn, Benjamin Dudoignon, Alexis Mendoza, Antoine Cuvelier, Jean-Francois Muir, Boris Melloni, Jean-Francois Chabot, Jesus Gonzalez-Bermejo, Maxime Patout
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Infectious Diseases
Rishma Amarsy, David Trystram, Emmanuelle Cambau, Catherine Monteil, Sandra Fournier, Juliette Oliary, Helga Junot, Pierre Sabatier, Raphael Porcher, Jerome Robert, Vincent Jarlier
Summary: This study measured the impact of the first wave of COVID-19 on the incidence of bloodstream infections at the largest multisite public healthcare institution in France. The results showed that the COVID-19 pandemic had a strong impact on hospital management and had unfavorable effects on severe infections, antimicrobial resistance, and laboratory work diagnostics.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Urology & Nephrology
Dorian Nezam, Raphael Porcher, Francois Grolleau, Pauline Morel, Dimitri Titeca-Beauport, Stanislas Faguer, Alexandre Karras, Justine Solignac, Noemie Jourde-Chiche, Francois Maurier, Hamza Sakhi, Khalil El Karoui, Rafik Mesbah, Pierre Louis Carron, Vincent Audard, Didier Ducloux, Romain Paule, Jean-Fracois Augusto, Julien Aniort, Aurelien Tiple, Cedric Rafat, Severine Beaudreuil, Xavier Puechal, Pierre Gobert, Ziad Massy, Catherine Hanrotel, Stephane Bally, Nihal Martis, Cecile-Audrey Durel, Geoffroy Desbuissons, Pascal Godmer, Aurelie Hummel, Francois Perrin, Antoine Neel, Claire De Moreuil, Tiphaine Goulenok, Dominique Guerrot, Steven Grange, Aurelie Foucher, Alban Deroux, Carole Cordonnier, Celine Guilbeau-Frugier, Anne Modesto-Segonds, Dominique Nochy, Laurent Daniel, Anissa Moktefi, Marion Rabant, Loic Guillevin, Alexis Regent, Benjamin Terrier
Summary: The study found that PLEX did not improve the primary outcome in the entire population, but identified a subset of patients who could benefit from PLEX. However, these findings need to be validated before being used in clinical decision making.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Respiratory System
Pauline Smondack, Francis-Edouard Gravier, Yann Combret, Jean-Francois Muir, Antoine Cuvelier, David Debeaumont, Clement Medrinal, Guillaume Prieur, Tristan Bonnevie
Summary: This study found that the location of exercise sessions during pulmonary rehabilitation influences patients' decisions to refuse or accept center-based educational workshops. When center-based programs are limited and exercise training is relocated to the patient's home, educational workshops should also be relocated to improve participation rates.
EXPERT REVIEW OF RESPIRATORY MEDICINE
(2022)
Letter
Urology & Nephrology
Dorian Nezam, Raphael Porcher, Francois Grolleau, Benjamin Terrier, French Vasculitis Study Grp
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Medicine, General & Internal
Manon Egnell, Isabelle Boutron, Sandrine Peneau, Pauline Ducrot, Mathilde Touvier, Pilar Galan, Leopold Fezeu, Raphael Porcher, Philippe Ravaud, Serge Hercberg, Emmanuelle Kesse-Guyot, Chantal Julia
Summary: This study investigated the effect of the Nutri-Score label on the nutritional quality of purchasing intentions among adults suffering from cardiometabolic diseases. The results showed that the Nutri-Score led to healthier food choices and higher nutritional quality in their shopping carts.
Article
Medicine, General & Internal
Charlotte Debras, Eloi Chazelas, Laury Sellem, Raphael Porcher, Nathalie Druesne-Pecollo, Younes Esseddik, Fabien Szabo de Edelenyi, Cedric Agaesse, Alexandre De Sa, Rebecca Lutchia, Leopold K. Fezeu, Chantal Julia, Emmanuelle Kesse-Guyot, Benjamin Alles, Pilar Galan, Serge Hercberg, Melanie Deschasaux-Tanguy, Inge Huybrechts, Bernard Srour, Mathilde Touvier
Summary: This large-scale prospective cohort study found a potential direct association between higher artificial sweetener consumption (especially aspartame, acesulfame potassium, and sucralose) and increased risk of cardiovascular diseases.
BMJ-BRITISH MEDICAL JOURNAL
(2022)
Article
Health Care Sciences & Services
Dimitris Mavridis, Adriani Nikolakopoulou, Irini Moustaki, Anna Chaimani, Raphael Porcherd, Isabelle Boutron, Philippe Ravaud
Summary: This study presents graphical methods to group interventions and uses conjoint analysis to place weights on outcomes based on stakeholders' preferences. The results provide valuable information about the clustering of interventions. Grouping interventions helps decision makers identify optimal options in terms of benefit-risk balance and choose interventions from the best cluster based on other factors such as cost and implementation.
JOURNAL OF CLINICAL EPIDEMIOLOGY
(2023)
Article
Respiratory System
Francis-Edouard Gravier, Joren Buekers, Pauline Smondack, Fairuz Boujibar, Guillaume Prieur, Clement Medrinal, Yann Combret, Jean-Francois Muir, Jean-Marc Baste, Antoine Cuvelier, David Debeaumont, Tristan Bonnevie
Summary: This study aimed to explore the feasibility of using oxygen uptake and heart rate as measures to evaluate the response to a prehabilitation program in patients with non-small cell lung cancer (NSCLC). The results showed that after a 15-session prehabilitation program, there were improvements in oxygen uptake and heart rate during exercise. These results support the concept of a faster adaptation of aerobic metabolism through prehabilitation training.
Review
Hematology
Jerome Lambert, Etienne Lengline, Raphael Porcher, Rodolphe Thiebaut, Sarah Zohar, Sylvie Chevret
Summary: In the past decade, it has become common practice to provide rapid answers and early patient access to innovative treatments in the absence of randomized clinical trials. This trend is particularly important in oncology when evaluating new targeted therapies. This article provides guidelines for the critical appraisal of comparisons or conducting single-arm trials, using the example of ciltacabtagene autoleucel for the treatment of relapsed or refractory multiple myeloma.
Article
Hematology
Florie Brion Bouvier, Raphael Porcher
Summary: The preferred approach to compare two treatments is a randomized controlled trial (RCT) which ensures similarity between groups and allows causal conclusions. When RCTs are not possible, observational data can be used to infer treatment effectiveness under certain assumptions, using regression modeling or propensity score methods. Target trial emulation principles are also discussed.
BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY
(2023)
Letter
Respiratory System
J. Sutter, A. Cuvelier, R. Lukaszewicz, J. Maris, I. Arnulf, T. Similowski, M. Patout
Summary: Chronic respiratory diseases deteriorate sleep, but nocturnal noninvasive ventilation can restore sleep quality. This study aimed to evaluate the sleep quality and its impact on quality of life in patients undergoing NIV without PSG guidance.
Article
Radiology, Nuclear Medicine & Medical Imaging
Georg J. Wengert, Yohann Dabi, Edith Kermarrec, Aurelie Jalaguier-Coudray, Edouard Poncelet, Raphael Porcher, Isabelle Thomassin-Naggara, Andrea G. Rockall
Summary: TIC assessment of dynamic contrast-enhanced MRI scans is more accurate than visual assessment for categorizing adnexal lesions and evaluating the O-RADS MRI score.
