The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.

The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.

The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.

The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.

The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.

Stearoyl-coenzyme A desaturase 1 (SCD1) catalyzes the rate-limiting step of de novo lipogenesis and modulates lipid homeostasis. Although numerous SCD1 inhibitors were tested for treating metabolic disorders both in preclinical and clinic studies, the tissue-specific roles of SCD1 in modulating obesity-associated metabolic disorders and determining the pharmacological effect of chemical SCD1 inhibition remain unclear. Here a novel role for intestinal SCD1 in obesity-associated metabolic disorders was uncovered. Intestinal SCD1 was found to be induced during obesity progression both in humans and mice. Intestine-specific, but not liver-specific, SCD1 deficiency reduced obesity and hepatic steatosis. A939572, an SCD1-specific inhibitor, ameliorated obesity and hepatic steatosis dependent on intestinal, but not hepatic, SCD1. Mechanistically, intestinal SCD1 deficiency impeded obesity-induced oxidative stress through its novel function of inducing metallothionein 1 in intestinal epithelial cells. These results suggest that intestinal SCD1 could be a viable target that underlies the pharmacological effect of chemical SCD1 inhibition in the treatment of obesity-associated metabolic disorders.

Background: s/Aims: The guidelines regarding the management of intraductal papillary mucinous neoplasms (IPMNs) all have slightly different surgical indications for high-risk lesions. We aim to retrospectively compare the accuracy of four guidelines in recommending surgery for high-risk IPMNs, and assess the accuracy of elevated CA-19-9 levels and imaging characteristics of IPMNs considered high-risk in predicting malignancy or high-grade dysplasia (HGD). Methods: The final histopathological diagnosis of surgically resected high-risk IPMNs during 2013−2020 were compared to preoperative surgical indications, as enumerated in four guidelines: the 2015 American Gastroenterological Association (AGA), 2017 International Consensus, 2018 European Study Group, and 2018 American College of Gastroenterology (ACG). Surgery was considered “justified” if histopathology of the surgical specimen showed HGD/malignancy, or there was postoperative symptomatic improvement. Results: Surgery was postoperatively justified in 26/65 (40.0%) cases. All IPMNs with HGD/malignancy were detected by the 2018 ACG and the combined (absolute and relative criteria) 2018 European guidelines. The combined (“high-risk stigmata” and “worrisome features”) 2017 International guideline missed 1/19 (5.3%) IPMNs with HGD/malignancy. The 2015 AGA guideline missed the most cases (11/19, 57.9%) of IPMNs with HGD/malignancy. We found the features most-associated with HGD/malignancy were pancreatic ductal dilation, and elevated CA-19-9 levels. Conclusions Following the 2015 AGA guideline results in the highest rate of missed HGD/malignancy, but the lowest rate of operating on IPMNs without these features; meanwhile, the 2018 ACG and the combined (absolute and relative criteria) 2018 European guidelines result in more operations for IPMNs without HGD/malignancy, but the lowest rates of missed HGD/malignancy in IPMNs.

Background: s/Aims: The guidelines regarding the management of intraductal papillary mucinous neoplasms (IPMNs) all have slightly different surgical indications for high-risk lesions. We aim to retrospectively compare the accuracy of four guidelines in recommending surgery for high-risk IPMNs, and assess the accuracy of elevated CA-19-9 levels and imaging characteristics of IPMNs considered high-risk in predicting malignancy or high-grade dysplasia (HGD). Methods: The final histopathological diagnosis of surgically resected high-risk IPMNs during 2013−2020 were compared to preoperative surgical indications, as enumerated in four guidelines: the 2015 American Gastroenterological Association (AGA), 2017 International Consensus, 2018 European Study Group, and 2018 American College of Gastroenterology (ACG). Surgery was considered “justified” if histopathology of the surgical specimen showed HGD/malignancy, or there was postoperative symptomatic improvement. Results: Surgery was postoperatively justified in 26/65 (40.0%) cases. All IPMNs with HGD/malignancy were detected by the 2018 ACG and the combined (absolute and relative criteria) 2018 European guidelines. The combined (“high-risk stigmata” and “worrisome features”) 2017 International guideline missed 1/19 (5.3%) IPMNs with HGD/malignancy. The 2015 AGA guideline missed the most cases (11/19, 57.9%) of IPMNs with HGD/malignancy. We found the features most-associated with HGD/malignancy were pancreatic ductal dilation, and elevated CA-19-9 levels. Conclusions Following the 2015 AGA guideline results in the highest rate of missed HGD/malignancy, but the lowest rate of operating on IPMNs without these features; meanwhile, the 2018 ACG and the combined (absolute and relative criteria) 2018 European guidelines result in more operations for IPMNs without HGD/malignancy, but the lowest rates of missed HGD/malignancy in IPMNs.

Background: s/Aims: The guidelines regarding the management of intraductal papillary mucinous neoplasms (IPMNs) all have slightly different surgical indications for high-risk lesions. We aim to retrospectively compare the accuracy of four guidelines in recommending surgery for high-risk IPMNs, and assess the accuracy of elevated CA-19-9 levels and imaging characteristics of IPMNs considered high-risk in predicting malignancy or high-grade dysplasia (HGD). Methods: The final histopathological diagnosis of surgically resected high-risk IPMNs during 2013−2020 were compared to preoperative surgical indications, as enumerated in four guidelines: the 2015 American Gastroenterological Association (AGA), 2017 International Consensus, 2018 European Study Group, and 2018 American College of Gastroenterology (ACG). Surgery was considered “justified” if histopathology of the surgical specimen showed HGD/malignancy, or there was postoperative symptomatic improvement. Results: Surgery was postoperatively justified in 26/65 (40.0%) cases. All IPMNs with HGD/malignancy were detected by the 2018 ACG and the combined (absolute and relative criteria) 2018 European guidelines. The combined (“high-risk stigmata” and “worrisome features”) 2017 International guideline missed 1/19 (5.3%) IPMNs with HGD/malignancy. The 2015 AGA guideline missed the most cases (11/19, 57.9%) of IPMNs with HGD/malignancy. We found the features most-associated with HGD/malignancy were pancreatic ductal dilation, and elevated CA-19-9 levels. Conclusions Following the 2015 AGA guideline results in the highest rate of missed HGD/malignancy, but the lowest rate of operating on IPMNs without these features; meanwhile, the 2018 ACG and the combined (absolute and relative criteria) 2018 European guidelines result in more operations for IPMNs without HGD/malignancy, but the lowest rates of missed HGD/malignancy in IPMNs.

Humans ; Sarcoma ; NFATC Transcription Factors ; RNA-Binding Protein EWS