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- Agrawal, K., et al.
(författare)
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Allergic sensitization impairs lung resident memory CD8 T-cell response and virus clearance
- 2022
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749. ; 150:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with asthma often suffer from frequent respiratory viral infections and reduced virus clearance. Lung resident memory T cells provide rapid protection against viral reinfections. Objective: Because the development of resident memory T cells relies on the lung microenvironment, we investigated the impact of allergen sensitization on the development of virus-specific lung resident memory T cells and viral clearance. Methods: Mice were sensitized with house dust mite extract followed by priming with X47 and a subsequent secondary influenza infection. Antiviral memory T-cell response and protection to viral infection was assessed before and after secondary influenza infection, respectively. Gene set variation analysis was performed on data sets from the U-BIOPRED asthma cohort using an IFN-γ–induced epithelial cell signature and a tissue resident memory T-cell signature. Results: Viral loads were higher in lungs of sensitized compared with nonsensitized mice after secondary infection, indicating reduced virus clearance. X47 priming induced fewer antiviral lung resident memory CD8 T cells and resulted in lower pulmonary IFN-γ levels in the lungs of sensitized as compared with nonsensitized mice. Using data from the U-BIOPRED cohort, we found that patients with enrichment of epithelial IFN-γ–induced genes in nasal brushings and bronchial biopsies were also enriched in resident memory T-cell–associated genes, had more epithelial CD8 T cells, and reported significantly fewer exacerbations. Conclusions: The allergen-sensitized lung microenvironment interferes with the formation of antiviral resident memory CD8 T cells in lungs and virus clearance. Defective antiviral memory response might contribute to increased susceptibility of patients with asthma to viral exacerbations.
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- Gandaglia, Giorgio, et al.
(författare)
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Clinical Characterization of Patients Diagnosed with Prostate Cancer and Undergoing Conservative Management : A PIONEER Analysis Based on Big Data
- 2024
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Ingår i: European Urology. - 0302-2838. ; 85:5, s. 457-465
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Tidskriftsartikel (refereegranskat)abstract
- Background: Conservative management is an option for prostate cancer (PCa) patients either with the objective of delaying or even avoiding curative therapy, or to wait until palliative treatment is needed. PIONEER, funded by the European Commission Innovative Medicines Initiative, aims at improving PCa care across Europe through the application of big data analytics. Objective: To describe the clinical characteristics and long-term outcomes of PCa patients on conservative management by using an international large network of real-world data. Design, setting, and participants: From an initial cohort of >100 000 000 adult individuals included in eight databases evaluated during a virtual study-a-thon hosted by PIONEER, we identified newly diagnosed PCa cases (n = 527 311). Among those, we selected patients who did not receive curative or palliative treatment within 6 mo from diagnosis (n = 123 146). Outcome measurements and statistical analysis: Patient and disease characteristics were reported. The number of patients who experienced the main study outcomes was quantified for each stratum and the overall cohort. Kaplan-Meier analyses were used to estimate the distribution of time to event data. Results and limitations: The most common comorbidities were hypertension (35–73%), obesity (9.2–54%), and type 2 diabetes (11–28%). The rate of PCa-related symptomatic progression ranged between 2.6% and 6.2%. Hospitalization (12–25%) and emergency department visits (10–14%) were common events during the 1st year of follow-up. The probability of being free from both palliative and curative treatments decreased during follow-up. Limitations include a lack of information on patients and disease characteristics and on treatment intent. Conclusions: Our results allow us to better understand the current landscape of patients with PCa managed with conservative treatment. PIONEER offers a unique opportunity to characterize the baseline features and outcomes of PCa patients managed conservatively using real-world data. Patient summary: Up to 25% of men with prostate cancer (PCa) managed conservatively experienced hospitalization and emergency department visits within the 1st year after diagnosis; 6% experienced PCa-related symptoms. The probability of receiving therapies for PCa decreased according to time elapsed after the diagnosis.
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