Article
Critical Care Medicine
Yi-Hui Zhou, Paul J. Gallins, Rhonda G. Pace, Hong Dang, Melis A. Aksit, Elizabeth E. Blue, Kati J. Buckingham, Joseph M. Collaco, Anna V. Faino, William W. Gordon, Kurt N. Hetrick, Hua Ling, Weifang Liu, Frankline M. Onchiri, Kymberleigh Pagel, Elizabeth W. Pugh, Karen S. Raraigh, Margaret Rosenfeld, Quan Sun, Jia Wen, Yun Li, Harriet Corvol, Lisa J. Strug, Michael J. Bamshad, Scott M. Blackman, Garry R. Cutting, Ronald L. Gibson, Wanda K. O'Neal, Fred A. Wright, Michael R. Knowles
Summary: This study aims to identify genetic modifier loci associated with pulmonary disease severity in patients with cystic fibrosis. The research used whole-genome sequencing data and genetic genotypes to discover two loci associated with lung disease. These findings support mechanistic studies and the development of novel therapeutics for CF lung disease.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Review
Gastroenterology & Hepatology
Jennifer Scott, Andrew M. Jones, Karen Piper Hanley, Varinder S. Athwal
Summary: This review provides a summary of the current understanding of cystic fibrosis-related liver disease (CFLD) in terms of its epidemiology, pathology, diagnosis, and management. The review highlights the heterogeneity of CFLD and the challenges in its diagnosis and treatment. The authors emphasize the lack of precise diagnostic strategies and effective therapies for CFLD, and the need for further research on its pathogenesis and disease detection.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Multidisciplinary Sciences
Jennifer A. Scott, Elliot Jokl, Timothy Gordon-Walker, Neil A. Hanley, Karen Piper Hanley, Varinder S. Athwal, Andrew M. Jones, Peter J. Barry
Summary: This study assessed diagnostic tools for liver fibrosis in patients with cystic fibrosis, finding that current guidelines may underestimate fibrosis while newer methods provide more accurate results. The authors proposed a new diagnostic criterion, which was validated in an independent cohort and accurately predicted liver disease in cystic fibrosis patients.
Article
Gastroenterology & Hepatology
Shruti Sakhuja, Heather M. Staples, Charles G. Minard, Louise E. Ramm, Peter J. Lewindon, Grant A. Ramm, Daniel H. Leung
Summary: This study aimed to evaluate the clinical utility of lung function and liver biomarkers assessed years prior to liver biopsy-proven CFLD in predicting the risk of severe fibrosis development. The findings suggest that mild-moderate pulmonary dysfunction and higher liver biomarker indices at baseline may be associated with faster progression of CFLD.
LIVER INTERNATIONAL
(2023)
Review
Gastroenterology & Hepatology
Jeremy Dana, Dominique Debray, Aurelie Beaufrere, Sophie Hillaire, Monique Fabre, Caroline Reinhold, Thomas F. Baumert, Laureline Berteloot, Valerie Vilgrain
Summary: Cystic fibrosis-related liver disease (CFLD) is a pathological mechanism caused by the defect in biliary epithelial cells in cystic fibrosis patients. CFLD presents with varying clinical/histological manifestations and severity, with focal biliary fibrosis being the main histological presentation. A minority of cases develop portal hypertension, requiring specific management including liver transplantation. Noncirrhotic portal hypertension, in addition to cirrhotic portal hypertension, is also increasingly prevalent. Accurate classification of CFLD is necessary for evaluating the effect of new therapies on the liver.
JOURNAL OF HEPATOLOGY
(2022)
Article
Pediatrics
Raphael Enaud, Eric Frison, Sophie Missonnier, Aude Fischer, Victor de Ledinghen, Paul Perez, Stephanie Bui, Michael Fayon, Jean-Francois Chateil, Thierry Lamireau
Summary: This study evaluated the repeatability and reproducibility of TE and pSWE VTQ in children with CF, finding both techniques to be reliable for assessing liver fibrosis. The high ICC values obtained suggest that TE and pSWE VTQ can be used effectively in the follow-up of CF patients, depending on their availability in CF centers.
PEDIATRIC RESEARCH
(2022)
Review
Genetics & Heredity
Afsoon Sepahzad, Deborah J. Morris-Rosendahl, Jane C. Davies
Summary: The understanding of cystic fibrosis has greatly improved since the discovery of the CFTR gene in 1989, leading to the development of modulator therapies targeted at mutations in CFTR. However, variations in treatment response and disease severity may be influenced by non-CFTR modifiers, highlighting the importance of studying the interaction between genetic and environmental factors. Efforts to personalize care and improve treatment outcomes should focus on understanding the relative influence of genomic versus environmental factors.
Article
Pediatrics
Amel El-Faramawy, Samya Z. Nasr, Mohamed M. S. Al Emam, Heba M. H. Fahmy
Summary: CFLD is common in Egyptian pwCF. Risk factors for CFLD include male sex, severe genetic mutations, long duration of CF, early onset, pancreatic insufficiency, history of meconium ileus, diabetes mellitus, and severe lung disease.
PEDIATRIC PULMONOLOGY
(2023)
Article
Genetics & Heredity
Melis A. Aksit, Hua Ling, Rhonda G. Pace, Karen S. Raraigh, Frankline Onchiri, Anna V. Faino, Kymberleigh Pagel, Elizabeth Pugh, Adrienne M. Stilp, Quan Sun, Elizabeth E. Blue, Fred A. Wright, Yi-Hui Zhou, Michael J. Bamshad, Ronald L. Gibson, Michael R. Knowles, Garry R. Cutting, Scott M. Blackman
Summary: Cystic fibrosis-related diabetes (CFRD) and meconium ileus (MI) are common gastrointestinal complications in individuals with cystic fibrosis (CF), and their genetic characteristics partially overlap. Through genome-wide association analysis, we identified new genetic loci associated with these two complications, revealing further genetic correlations and overlaps between them.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Andrew D. Graustein, William R. Berrington, Kati J. Buckingham, Felicia K. Nguyen, Lara L. Joudeh, Margaret Rosenfeld, Michael J. Bamshad, Ronald L. Gibson, Thomas R. Hawn, Mary J. Emond
Summary: Specific variants in the NLRP3 and NLRC4 pathways were found to be associated with different outcomes in children with CF, serving as potential targets for therapy. Through knockout experiments and genetic analysis, high-risk children could be identified and treatment choices could be guided.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2021)
Article
Gastroenterology & Hepatology
Luke C. Pilling, Janice L. Atkins, David Melzer
Summary: This study found that common genetic variants may influence the disease risk for individuals carrying HFE gene mutations, including liver fibrosis, liver cancer, osteoarthritis, and diabetes.
Review
Medicine, General & Internal
Agnes Rita Martonosi, Alexandra Soos, Zoltan Rumbus, Peter Hegyi, Vera Izsak, Piroska Pazmany, Marcell Imrei, Szilard Vancsa, Zsolt Szakacs, Andrea Parniczky
Summary: This study ranked different non-invasive diagnostic methods for cystic fibrosis-related liver disease (CFLD) and found that the New criteria had the best diagnostic performance. Transient elastography was identified as a simple, affordable, and effective tool for detecting CFLD, outperforming other imaging, biochemical, and fibrosis tests. Further validation studies are needed to confirm these findings.
FRONTIERS IN MEDICINE
(2021)
Review
Medicine, General & Internal
Fernanda Iafusco, Giovanna Maione, Francesco Maria Rosanio, Enza Mozzillo, Adriana Franzese, Nadia Tinto
Summary: Cystic fibrosis, caused by mutations in the CFTR gene, is the most common autosomal recessive disease in the Caucasian population. Cystic fibrosis-related diabetes (CFRD) is a common nonpulmonary complication, with a prevalence that increases with age and is influenced by various factors. Genetic factors, including CFTR genotype, play a role in the development of CFRD.
Review
Pharmacology & Pharmacy
Alessandro Rimessi, Veronica A. M. Vitto, Simone Patergnani, Paolo Pinton
Summary: Cystic fibrosis is a genetic disorder characterized by airway issues and lung damage. Calcium signaling plays a crucial role in the pathophysiology of CF lung disease, with dysregulated calcium signals leading to impaired cell function and exacerbated inflammation.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Respiratory System
Ao Sasame, Diarmuid Stokes, Billy Bourke, Lucy Connolly, Emer Fitzpatrick, Marion Rowland
Summary: This systematic review evaluates the impact of liver disease on mortality in CF patients. The results show that liver disease shortens the life expectancy of CF patients, with pulmonary complications being the primary cause of death.
JOURNAL OF CYSTIC FIBROSIS
(2022)
Article
Gastroenterology & Hepatology
Laura Zazzeron, Gianfranco Alicandro, Valeria Dacco, Chiara Lanfranchi, Anna Bulfamante, Calogero Sathya Sciarrabba, Fabiola Corti, Carla Colombo
Summary: This study found that the use of proton pump inhibitors (PPI) as adjuvant therapy in people with cystic fibrosis (pwCF) may increase the risk of respiratory infection and does not improve nutritional status.
DIGESTIVE AND LIVER DISEASE
(2023)
Article
Respiratory System
Adele Coriati, Xiayi Ma, Jenna Sykes, Sanja Stanojevic, Rasa Ruseckaite, Lydie Lemonnier, Clemence Dehillotte, Jan Tate, Catherine Ann Byrnes, Scott C. Bell, Pierre Regis Burgel, Anne L. Stephenson
Summary: This study compared the survival rates of cystic fibrosis patients in countries with single-payer healthcare systems, taking into account markers of disease severity. The results showed that France had significantly higher survival rates compared to other countries, despite having a higher proportion of underweight patients.
Article
Endocrinology & Metabolism
Simone De Leo, Matteo Trevisan, Carla Colombo, Claudia Moneta, Noemi Giancola, Laura Fugazzola
Summary: This retrospective cohort study aimed to investigate the incidence, characteristics, and management of hypocalcemia in patients with advanced thyroid cancer treated with lenvatinib. The study found a higher incidence of hypocalcemia (24%) compared to the registration trial (6.9%). The hypocalcemia in this cohort was caused by both PTH-dependent and PTH-independent mechanisms.
Article
Respiratory System
Carla Colombo, Grant A. Ramm, Anders Lindblad, Fabiola Corti, Luigi Porcaro, Federico Alghisi, Irina Asherova, Helen Evans, Nataliya Kashirskaya, Elena Kondratyeva, Peter J. Lewindon, Isabelle de Monestrol, Mark Oliver, Chee Y. Ooi, Rita Padoan, Sahana Shankar, Gianfranco Alicandro
Summary: Cystic-fibrosis-related liver disease (CFLD) is a variable phenotype of CF. CFTR modulator therapies, elexacaftor, tezacaftor, and ivacaftor (ETI), and ivacaftor (IVA), are available for CF patients. Genetic eligibility evaluation showed that 13% of patients without CFLD and 11% of patients with severe CFLD are not eligible for ETI or IVA therapy. Ineligible patients cannot benefit from these new treatments.
JOURNAL OF CYSTIC FIBROSIS
(2023)
Review
Genetics & Heredity
Victoria E. J. M. Palasantzas, Isabel Tamargo-Rubio, Kieu Le, Jelle Slager, Cisca Wijmenga, Iris H. Jonkers, Vinod Kumar, Jingyuan Fu, Sebo Withoff
Summary: Genome-wide association studies (GWAS) have identified numerous genetic variants associated with complex genetic diseases and drug efficacy. However, functional characterization of these variants is challenging due to the lack of human model systems. Organ-on-a-chip (OoC) platforms, enabled by advances in molecular and nanotechnology, provide personalized platforms for studying the impact of genetics and environment on organ physiology. This review highlights the technology and showcases the potential of OoCs in disease modeling and pharmacogenetic research.
TRENDS IN GENETICS
(2023)
Article
Microbiology
Daniela Antunes, Samuel M. Goncalves, Vasiliki Matzaraki, Claudia S. Rodrigues, Relber A. Goncales, Joana Rocha, Jorge Saiz, Antonio Marques, Egidio Torrado, Ricardo Silvestre, Fernando Rodrigues, Frank L. van de Veerdonk, Coral Barbas, Mihai G. Netea, Vinod Kumar, Cristina Cunha, Agostinho Carvalho
Summary: The fungal pathogen Aspergillus fumigatus can cause severe infections in immunocompromised patients. Cellular metabolism plays a crucial role in the immune response to this pathogen. This study highlights the importance of glutamine metabolism in macrophage activation and defense against A. fumigatus. Glutamine metabolism is essential for phagocytosis and cytokine production, and genetic variation in glutamine metabolism genes affects the response to fungal stimulation.
MICROBIOLOGY SPECTRUM
(2023)
Article
Endocrinology & Metabolism
Simone De Leo, Matteo Trevisan, Claudia Moneta, Carla Colombo
Summary: Tyrosine kinase inhibitors (TKIs) have shown improved outcomes for various tumors, but they can also cause adverse events and endocrine-related toxicities. The most common endocrinopathies caused by TKIs are thyroid dysfunction and hypothyroidism, with potential mechanisms including dysfunction of the thyroid gland and hormone metabolism impairment. TKIs can also affect other glands, leading to adrenal insufficiency, growth retardation, hypogonadism, and fertility impairment. TKIs can also disrupt bone metabolism and cause metabolic alterations, such as hypoglycemia and hyperglycemia. These endocrine-related adverse events should be managed by endocrinologists with replacement therapy or symptomatic treatment.
ANNALES D ENDOCRINOLOGIE
(2023)
Article
Immunology
Joseph E. Levitt, Haley Hedlin, Sophie Duong, Di Lu, Justin Lee, Bryan Bunning, Nadia Elkarra, Benjamin A. Pinsky, Eileen Heffernan, Eric Springman, Richard B. Moss, Hector F. Bonilla, Julie Parsonnet, Roham T. Zamanian, Jamison J. Langguth, Jenna Bollyky, Chaitan Khosla, Mark R. Nicolls, Manisha Desai, Angela J. Rogers
Summary: The study aimed to evaluate the effectiveness of Acebilustat in treating outpatients with COVID-19, and the results showed that the medication did not shorten symptom duration.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Laura Peretto, Elena Tonetto, Iva Maestri, Valentino Bezzerri, Roberto Valli, Marco Cipolli, Mirko Pinotti, Dario Balestra
Summary: Shwachman-Diamond syndrome (SDS) is a common inherited bone marrow failure syndrome caused by SBDS gene mutations. The mutation in the SBDS c.258+2T>C variant affects splicing, but some correct transcripts can still be produced, explaining the survival of SDS patients. Correction approaches at the RNA and DNA levels, such as engineered U1snRNA, trans-splicing, and base/prime editors, can partially counteract the mutation effect and lead to correctly spliced transcripts. DNA editors, in particular, may offer a potential innovative therapy for SDS by reverting the mutation and potentially selecting bone-marrow cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pediatrics
Valeria Dacco, Gianfranco Alicandro, Alessandra Consales, Chiara Rosazza, Calogero S. Sciarrabba, Lisa Cariani, Carla Colombo
Summary: This study provides insights into Cepacia syndrome (CS), a rare but potentially lethal complication of Burkholderia cepacia complex (BCC) infection in cystic fibrosis (CF) patients. The study includes a systematic review of 18 cases of CS reported over the last 24 years, with a high mortality rate of 50%. The data are insufficient to determine the most effective therapeutic approach for CS.
PEDIATRIC PULMONOLOGY
(2023)
Article
Health Care Sciences & Services
Simone Gambazza, Annalisa Orenti, Giovanna Pizzamiglio, Anna Zolin, Carla Colombo, Dario Laquintana, Federico Ambrogi, ECFSPR
Summary: This study aimed to understand the prognosis for people with cystic fibrosis (pwCF) on oxygen therapy (OT), evaluating the probability of lung transplantation (LTx) and death in pwCF with and without OT. The study found that OT is strongly associated with poor survival in pwCF, highlighting the importance of harmonizing CF care throughout European countries and minimizing the onset of pulmonary gas exchange abnormalities.
THERAPEUTICS AND CLINICAL RISK MANAGEMENT
(2023)
Article
Immunology
Collins K. Boahen, Roy Oelen, Kieu Le, Mihai G. Netea, Lude Franke, Monique G. P. van der Wijst, Vinod Kumar
Summary: Both gene expression and protein concentrations are regulated by genetic variants. Exploring the regulation of eQTLs and pQTLs simultaneously in a context- and cell-type dependent manner may help unravel the mechanistic basis for genetic regulation of pQTLs. By conducting meta-analysis of Candida albicans-induced pQTLs from two population-based cohorts and intersecting the results with Candida-induced cell-type specific expression association data (eQTL), we found systematic differences between pQTLs and eQTLs, indicating the limitation of using eQTLs as a proxy for pQTLs. Additionally, our study identified SNPs affecting protein networks and implicated specific genomic loci through colocalization of pQTLs and eQTLs signals.
FRONTIERS IN IMMUNOLOGY
(2023)
Correction
Microbiology
Richard B. B. Moss
Review
Endocrinology & Metabolism
Stefano Palomba, Carla Colombo, Andrea Busnelli, Donatella Caserta, Giovanni Vitale
Summary: This study comprehensively reviews the relationship between polycystic ovary syndrome (PCOS) and thyroid dysfunction by analyzing available evidence in nine main areas of interest. The results suggest that PCOS and thyroid disorders are closely related, and their coexistence may increase the reproductive and metabolic risk of patients. Regular screening for thyroid function and thyroid-specific autoantibodies in women with PCOS, particularly before and during pregnancy, is highly recommended.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Respiratory System
Rhonda Szczesniak, Eleni-Rosalina Andrinopoulou, Weiji Su, Pedro M. Afonso, Pierre-Regis Burgel, Elizabeth Cromwell, Emrah Gecili, Enas Ghulam, Christopher H. Goss, Nicole Mayer-Hamblett, Ruth H. Keogh, Theodore G. Liou, Bruce Marshall, Wayne J. Morgan, Joshua S. Ostrenga, David J. Pasta, Sanja Stanojevic, Claire Wainwright, Grace C. Zhou, Gabriela Fernandez, Aliza K. Fink, Michael S. Schechter
Summary: The study aims to estimate the rate of lung function decline in cystic fibrosis and examine the impact of different research methods on the results. The findings show that the choice of modeling strategy can affect the estimated rate of decline, but the results are generally reliable under specific scenarios.
ANNALS OF THE AMERICAN THORACIC SOCIETY
(2023)