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.

Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

In this study, we systematically tested the hypothesis that during the critical developmental period of adolescence, on a macro scale, the concentrations of major excitatory and inhibitory neurotransmitters (glutamate/glutamine and γ‑aminobutyric acid [GABA]) in the dorsal and ventral lateral prefrontal cortex are associated with the brain's functional connectivity and an individual's psychopathology. Neurotransmitters were measured via magnetic resonance spectroscopy while functional connectivity was measured with resting-state fMRI (n = 121). Seed-based and network-based analyses revealed associations of neurotransmitter concentrations and functional connectivities between regions/networks that are connected to prefrontal cortices via structural connections that are thought to be under dynamic development during adolescence. These regions tend to be boundary areas between functional networks. Furthermore, several connectivities were found to be associated with individual's levels of internalizing psychopathology. These findings provide insights into specific neurochemical mechanisms underlying the brain's macroscale functional organization, its development during adolescence, and its potential associations with symptoms associated with internalizing psychopathology.
Humans ; Adolescent ; Glutamic Acid/metabolism* ; Prefrontal Cortex/diagnostic imaging* ; Male ; Glutamine/metabolism* ; Female ; gamma-Aminobutyric Acid/metabolism* ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Nerve Net/metabolism* ; Neural Pathways ; Connectome

Background: Severe and critical COVID-19 disease is characterized by hyperinflammation involving pro-inflammatory cytokines, particularly IL-6. Tocilizumab is a monoclonal antibody that blocks IL-6 receptors. Objectives: This study evaluated the efficacy of tocilizumab in Filipino patients with severe to critical COVID-19 disease. Methods: This phase 3 randomized double-blind trial, included patients hospitalized for severe or critical COVID-19 in a 1:1 ratio to receive either tocilizumab plus local standard of care or placebo plus standard of care. Patients were eligible for a repeat IV infusion within 24-48 hours if they deteriorated or did not improve. Treatment success or clinical improvement was defined as at least two categories of improvement from baseline in the WHO 7-point Ordinal Scale of patient status, in an intention-to-treat manner. Results: Forty-nine (49) patients were randomized in the tocilizumab arm and 49 in the placebo arm. There was no significant difference in age, comorbidities, COVID-19 severity, need for mechanical ventilation, presence of acute respiratory distress syndrome, or biomarker levels between groups. Use of adjunctive therapy was similar between groups, with corticosteroid used in 91.8% in tocilizumab group and 81.6% in the placebo group, while remdesivir was used in 98% of participants in both groups. There was no significant difference between groups in terms of treatment success in both the intention-to-treat analysis (relative risk=1.05, 95% CI: 0.85-1.30) and per-protocol analysis (relative risk=0.98, 95% CI: 0.80 to 1.21). There was no significant difference in time to improvement of at least two categories relative to baseline on the 7-point Ordinal Scale of clinical status. Conclusion The use of tocilizumab on top of standard of care in the management of patients with severe to critical COVID-19 did not result in significant improvement as defined by the WHO 7-point Ordinal Scale of patient status, nor in significant improvement in incidence of mechanical ventilation, incidence of ICU admission, length of ICU stay, and mortality rate.
COVID-19 ; Interleukin-6

Background: Global longitudinal strain (GLS) is a useful marker for the echocardiographic evaluation of left ventricular (LV) systolic dysfunction. Presently GLS is derived from speckle tracking of LV images, but speckle tracking software is not always available. We seek to determine if manually measured GLS (MM-GLS) by assessing mid-myocardial lengths can be a reliable alternative to speckle tracking GLS (ST-GLS). Methods: Transthoracic echocardiogram images of a tertiary hospital in Australia were retrospectively analyzed to study the relationships between ST-GLS, MM-GLS, and LV ejection fraction (LVEF). We further evaluated the impact of image quality and regional wall motion abnormalities on those relationships. Results: Echocardiography studies from 154 patients were included (female sex, 36%; mean age, 61.7 ± 14.8 years).The average LVEF was 51.3% ± 11.3% and the average ST-GLS was 16.7 ± 3.8. MM-GLS strongly correlated with ST-GLS (intraclass correlation coefficient, 0.986; P < 0.001) and with LVEF regardless of the presence of regional wall motion abnormalities. If using GLS cutoff of more than 18% as normal, 97.5% of studies with normal ST-GLS had normal MM-GLS. If using GLS cutoff as less than 16% as abnormal, 95.5% of studies with abnormal ST-GLS had abnormal MM-GLS. There was no case with ST-GLS > 18% and MM-GLS < 16%, nor were there any case in with ST-GLS < 16% and  MM-GLS > 18%. Conclusions MM-GLS correlates strongly with ST-GLS. If ST-GLS cannot be accurately assessed, MM-GLS may be a useful alternative to provide GLS values in both clinical and research studies.

Background: Global longitudinal strain (GLS) is a useful marker for the echocardiographic evaluation of left ventricular (LV) systolic dysfunction. Presently GLS is derived from speckle tracking of LV images, but speckle tracking software is not always available. We seek to determine if manually measured GLS (MM-GLS) by assessing mid-myocardial lengths can be a reliable alternative to speckle tracking GLS (ST-GLS). Methods: Transthoracic echocardiogram images of a tertiary hospital in Australia were retrospectively analyzed to study the relationships between ST-GLS, MM-GLS, and LV ejection fraction (LVEF). We further evaluated the impact of image quality and regional wall motion abnormalities on those relationships. Results: Echocardiography studies from 154 patients were included (female sex, 36%; mean age, 61.7 ± 14.8 years).The average LVEF was 51.3% ± 11.3% and the average ST-GLS was 16.7 ± 3.8. MM-GLS strongly correlated with ST-GLS (intraclass correlation coefficient, 0.986; P < 0.001) and with LVEF regardless of the presence of regional wall motion abnormalities. If using GLS cutoff of more than 18% as normal, 97.5% of studies with normal ST-GLS had normal MM-GLS. If using GLS cutoff as less than 16% as abnormal, 95.5% of studies with abnormal ST-GLS had abnormal MM-GLS. There was no case with ST-GLS > 18% and MM-GLS < 16%, nor were there any case in with ST-GLS < 16% and  MM-GLS > 18%. Conclusions MM-GLS correlates strongly with ST-GLS. If ST-GLS cannot be accurately assessed, MM-GLS may be a useful alternative to provide GLS values in both clinical and research studies.