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.

Purpose: Conventional therapies and surgery remain the standard treatment for breast cancer. However, combating the eventual development of metastasis is still a challenge.Newcastle disease virus (NDV) is one of the various species of viruses under clinical evaluation as a vector for oncolytic, gene-, and immune-stimulating therapies. The purpose of this study was to evaluate the antitumor activity of a recombinant NDV (rNDV-P05) in a breast cancer murine model. Methods: Tumors were induced by injecting the cellular suspension (4T1 cell line) subcutaneously. The virus strain P05 was applied three times at intervals of seven days, starting seven days after tumor induction, and was completed 21 days later. Determination of tumor weight, spleen index, and lung metastasis were done after sacrificing the mice.Serum levels of interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α, and TNF-related apoptosis-inducing ligand (TRAIL) were quantified by enzyme-linked immunosorbent assay.CD8+ infiltrated cells were analyzed by immunofluorescence. Results: rNDV-P05 showed a route-of-administration-dependent effect, demonstrating that the systemic administration of the virus significantly reduces the tumor mass and volume, spleen index, and abundance of metastatic clonogenic colonies in lung tissue, and increases the inhibition rate of the tumor. The intratumoral administration of rNDV-P05 was ineffective for all the parameters evaluated. Antitumor and antimetastatic capability of rNDV-P05 is mediated, at least partially, through its immune-stimulatory effect on the upregulation of TNF-α, TRAIL, IFN-α, and IFN-γ, and its ability to recruit CD8+ T cells into tumor tissue. Conclusion Systemic treatment with rNDV-P05 decreases the tumoral parameters in the breast cancer murine model.

Objective: To describe the roadmapping technique and our three-year experience in the management of intracranial aneurysms in the hybrid operating room. Methods: We analyzed all patients who underwent surgical clipping for cerebral aneurysms with the roadmapping technique from January 2017 to September 2019. We report demographic, clinical, and morphological variables, as well as clinical and radiological outcomes. We further describe three illustrative cases of the technique. Results: A total of 13 patients were included, 9 of which (69.2%) presented with subarachnoid hemorrhage, with a total of 23 treated aneurysms. All patients were female, with a mean age of 47.7 years (range 31-63). All cases were anterior circulation aneurysms, the most frequent location being the ophthalmic segment of the internal carotid artery (ICA) in 11 cases (48%), followed by posterior communicating in 8 (36%), and ICA bifurcation in 2 (8%). Intraoperative clip repositioning was required in 9 aneurysms (36%) as a result of the roadmapping technique in the hybrid operating room. There were no residual aneurysms in our series, nor reported mortality. Conclusions The roadmapping technique in the hybrid operating room offers a complementary tool for the adequate occlusion of complex intracranial aneurysms, as it provides a real time fluoroscopic-guided clipping technique, and clip repositioning is possible in a single surgical stage, whenever a residual portion of the aneurysm is identified. This technique also provides some advantages, such as immediate vasospasm identification and treatment with intra-arterial vasodilators, balloon proximal control for certain paraclinoid aneurysms, and simultaneous endovascular treatment in selected cases during a single stage.

Background: It is acknowledged that legislation acts as a motivator for organizational action on psychosocial risks. Our study aims to provide evidence on the relationship between key occupational safety and health (OSH) policy principles and organizational action on work-related stress, and, in turn, with reported employee job demands and resources and their experience of work-related stress. We focus on Italy where specific legislation and practices on work-related stress were introduced in 2008 which are underpinned by these key OSH policy principles. Methods: Secondary analysis of the Italian samples from the employer ESENER-2 and employee 6th EWCS surveys was conducted, using path analysis in structural equation modeling (SEM) linking the two datasets. Results: We found a strong statistically significant relationship between OSH policy principles and organizational action on work-related stress (C.I. = .62-.78 p < .001). The existence of an organizational action plan on work-related stress was found to be significantly associated with more reported job resources (C.I. = .02-.24, p < .05) but these were not found to be significantly associated with less work-related stress. No significant association was found between having an organizational action plan for work-related stress and reported job demands. However, job demands were significantly related to reported work-related stress (C.I. = .27-.47, p < .001). Conclusions Findings add support to the call for specific legislation on work-related psychosocial risks and highlight how an organizational OSH culture underpinned by key OSH principles, and awareness/competence development on psychosocial risk management can have a positive effect on organizational action. However, further support needs to be provided to organizations around developing primary prevention interventions at the organizational level with the aim of reducing job demands.

Obesity is a major worldwide health problem that is related to most chronic diseases, including male infertility. Owing to its wide impact on health, mechanisms underlying obesity-related infertility remain unknown. In this study, we report that mice fed a high-fat diet (HFD) for over 2 months showed reduced fertility rates and increased germ cell apoptosis, seminiferous tubule degeneration, and decreased intratesticular estradiol (E2) and E2-to-testosterone ratio. Interestingly, we also detected a decrease in testicular fatty acid levels, behenic acid (C22:0), and docosahexaenoic acid (DHA, 22:6n-3), which may be related to the production of dysfunctional spermatozoa. Overall, we did not detect any changes in the frequency of seminiferous tubule stages, sperm count, or rate of in vitro capacitation. However, there was an increase in spontaneous and progesterone-induced acrosomal exocytosis (acrosome reaction) in spermatozoa from HFD-fed mice. These data suggest that a decrease in E2 and fatty acid levels influences spermatogenesis and some steps of acrosome biogenesis that will have consequences for fertilization. Thus, our results add new evidence about the adverse effect of obesity in male reproduction and suggest that the acrosomal reaction can also be affected under this condition.

Purpose: The objective of the present study was to evaluate the efficacy of pasteurization, freezing, the addition of formaldehyde and peroxymonosulfate on the inactivation of the bovine leukemia virus (BLV) present in milk. Materials and Methods: A sheep bioassay was carried out in 40 sheep, which were intraperitoneally inoculated with leukocytes from milk infected by the BLV previously treated with one of the virus inactivation methods. Five study groups were evaluated: (1) control group: milk without previous treatment, (2) pasteurization group: milk treated by pasteurization, (3) freezing group: milk treated by freezing for 36 hours, (4) formaldehyde group: 0.1% formaldehyde, and (5) peroxymonosulfate group: 0.05% peroxymonosulfate. The inoculated animals were followed for 10 weeks. Results: At week 10 post-inoculation, all the animals (8/8) of the control group and the peroxymonosulfate group were seropositive to BLV, while no animals were seropositive (0/8) to BLV in the remaining three groups. Statistically significant differences were found between the pasteurization, freezing and formaldehyde groups with respect to the control (p < 0.001) and peroxymonosulfate groups (p < 0.001). Conclusion The results indicate that pasteurization, freezing and formaldehyde processes are efficient in inactivating the BLV and can be used in milk to prevent the transmission of the virus.