BackgroundPatients with chronic lung disease (CLD), such as asthma or chronic obstructive pulmonary disease, were expected to have an increased risk of clinical manifestations and severity of ...COVID-19. However, these comorbidities have been reported less frequently than expected. Chronic treatment with inhaled corticosteroids (ICS) may impact the clinical course of COVID-19. The main objective of this study is to know the influence of chronic treatment with ICS on the prognosis of COVID-19 hospitalized patients with CLD.MethodsA multicenter retrospective cohort study was designed, including patients hospitalized with COVID-19. Epidemiological and clinical data were collected at admission and at seven days, and clinical outcomes were collected. Patients with CLD with and without chronic treatment with ICS were compared.ResultsTwo thousand five hundred ninety-eight patients were included, of which 1,171 patients had a diagnosis of asthma and 1,427 of COPD (53.37% and 41.41% with ICS, respectively). No differences were found in mortality, transfer to ICU, or development of moderate-severe ARDS. Patients with chronic ICS had a longer hospital stay in both asthma and COPD patients (9 vs. 8 days, p = 0.031 in asthma patients), (11 vs. 9 days, p = 0.018 in COPD patients); although they also had more comorbidity burden.ConclusionsPatients with chronic inhaled corticosteroids had longer hospital stays and more chronic comorbidities, measured by the Charlson comorbidity index, but they did not have more severe disease at admission, evaluated with qSOFA and PSI scores. Chronic treatment with inhaled corticosteroids had no influence on the prognosis of patients with chronic lung disease and COVID-19.
The direct-instillation nasal allergen challenge (NAC) and the environmental exposure chamber (EEC) are 2 methods of conducting controlled allergen provocations. The clinical and biological ...comparability of these methods has not been thoroughly investigated.
We sought to compare clinical and immunologic responses to cat allergen in NAC versus EEC.
Twenty-four participants were randomized to receive either NAC followed by a 2-day challenge in an EEC or a 2-day challenge in an EEC followed by NAC. Challenges were separated by 28-day washout periods. We measured total nasal symptom scores, peak nasal inspiratory flow, nasal (0-8 hours) and serum cytokines, serum antibodies, peripheral blood antigen-specific T lymphocytes, and gene expression in nasal scrapings. The primary outcome was the total nasal symptom score area under the curve for the first 3 hours after allergen exposure in NAC or after initiation of exposure in EEC.
Both challenges increased IL-5 and IL-13 in nasal fluids and serum and resulted in altered nasal cell expression of gene modules related to mucosal biology and transcriptional regulation. Changes in gene modules, more so than cytokine measurements, showed significant associations with total nasal symptom score and peak nasal inspiratory flow. Overall, EEC exposure generated larger responses and more early terminations compared with NAC. Although the 2 challenges did not correlate in symptom magnitude or temporality, striking correlations were observed in cytokine levels.
Although clinical outcomes of NAC and EEC were temporally different and nonequivalent in magnitude, immunologic responses were similar. Selection of a particular allergen challenge method should depend on considerations of study objectives and cost.
We aimed to develop and validate a prediction model, based on clinical history and examination findings on initial diagnosis of coronavirus disease 2019 (COVID-19), to identify patients at risk of ...critical outcomes.
We used data from the SEMI-COVID-19 Registry, a cohort of consecutive patients hospitalized for COVID-19 from 132 centres in Spain (23rd March to 21st May 2020). For the development cohort, tertiary referral hospitals were selected, while the validation cohort included smaller hospitals. The primary outcome was a composite of in-hospital death, mechanical ventilation, or admission to intensive care unit. Clinical signs and symptoms, demographics, and medical history ascertained at presentation were screened using least absolute shrinkage and selection operator, and logistic regression was used to construct the predictive model.
There were 10 433 patients, 7850 in the development cohort (primary outcome 25.1%, 1967/7850) and 2583 in the validation cohort (outcome 27.0%, 698/2583). The PRIORITY model included: age, dependency, cardiovascular disease, chronic kidney disease, dyspnoea, tachypnoea, confusion, systolic blood pressure, and SpO2 ≤93% or oxygen requirement. The model showed high discrimination for critical illness in both the development (C-statistic 0.823; 95% confidence interval (CI) 0.813, 0.834) and validation (C-statistic 0.794; 95%CI 0.775, 0.813) cohorts. A freely available web-based calculator was developed based on this model (https://www.evidencio.com/models/show/2344).
The PRIORITY model, based on easily obtained clinical information, had good discrimination and generalizability for identifying COVID-19 patients at risk of critical outcomes.
Abstract Background: The phase 3 FRESCO-2 trial (NCT04322539) demonstrated a significant survival benefit with fruquintinib (F) + BSC vs placebo (P) + BSC as third or later line of therapy for ...patients (pts) with mCRC. Based on the results of FRESCO-2, F was FDA-approved for adults with previously treated mCRC, irrespective of biomarker status. In mCRC, CEA levels and imaging are routinely used to monitor response to systemic therapy. We investigated early CEA changes during treatment in FRESCO-2 and possible relationships with efficacy. Methods: Pts with abnormal baseline (BL) CEA were included based on local lab reference ranges. Serum CEA levels were measured at BL and Day 1 (D1) of each 28-day cycle (C) except C1. Changes in CEA levels were analyzed at C2D1 and C3D1. CEA response was defined as ≥50% decrease from BL, and CEA progression was defined as ≥100% increase from BL. Tumor evaluation was performed by CT or MRI scan every 2 cycles. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method; hazard ratio (HR) was estimated via Cox proportional hazards model; p-value was generated from log rank test. Results: Overall, 88.3% (407/461) vs 90.4% (208/230) of pts had abnormal BL CEA in F vs P arms; median BL CEA values were similar between treatment arms (Table). At C3D1, the proportion of pts who had a CEA response was significantly higher with F vs P (35.5% vs 3.8%, P <0.001) and the proportion who had CEA progression was significantly lower (5.7% vs 47.2%, P <0.001). Pts in the F arm with CEA response at C3D1 had improved OS and PFS vs pts without CEA response and pts with CEA progression (Table). These results were consistent for pts who had an early CEA response at C2D1 (Table). Conclusion: CEA response at C2D1 and C3D1 could be considered an early predictor for improved OS and PFS. Pts with CEA response seem to benefit from F + BSC compared with pts without response or with CEA progression. Table. CEA changes from baseline in pts in the F + BSC vs P + BSC arms, and OS and PFS based on CEA response in pts in the F + BSC arm CEA changes from baseline by treatment arm (ITT population) F + BSC (N=461) P + BSC (N=230) Baseline, n 407 208 Median CEA (range), µg/L 132.4 (3.0-213000.0) 169.6 (3.2-90010.0) C2D1, n 340 151 Median CEA (range), µg/L 93.3 (2.0-98660.0) 133.5 (2.7-255910.0) Median change from baseline (range), % -19.2 (-90.5-467.8) 44.2 (-61.7-606.8) C3D1, n 245 53 Median CEA (range), µg/L 78.3 (1.7-133390.0) 145.2 (3.9-17782.0) Median change from baseline (range), % -31.0 (-91.4-2195.8) 90.5 (-68.9-3776.6) OS and PFS for pts in the F + BSC arm with or without CEA response at C2D1 and C3D1 Pts with early CEA response at C2D1(n=66) Pts without early CEA response at C2D1 (n=274) Pts with CEA response at C3D1 (n=87) Pts without CEA response at C3D1 (n=158) Median OS, months 10.0 7.4 11.1 8.5 HR (95% CI), P value 0.62 (0.44-0.89), P = 0.009 0.65 (0.46-0.92), P = 0.015 Median PFS, months 5.6 3.7 5.8 4.2 HR (95% CI), P value 0.68 (0.51-0.92), P = 0.01 0.58 (0.44-0.78), P = 0.0003 OS and PFS for pts in the F + BSC arm with CEA response or CEA progression at C2D1 and C3D1 Pts with early CEA response at C2D1(n=66) Pts with early CEA progression at C2D1 (n=15) Pts with CEA response at C3D1 (n=87) Pts with CEA progression at C3D1 (n=14) Median OS, months 10.0 4.3 11.1 5.6 HR (95% CI), P value 0.27 (0.14-0.51), P <0.0001 0.23 (0.12-0.45), P <0.0001 Median PFS, months 5.6 1.9 5.8 3.4 HR (95% CI), P value 0.30 (0.16-0.56), P <0.0001 0.25 (0.13-0.48), P <0.0001 Citation Format: Sara Lonardi, Arvind Dasari, Rocio Garcia-Carbonero, Takayuki Yoshino, Pilar García-Alfonso, Judit Kocsis, Chiara Cremolini, François Ghiringhelli, Ardaman Shergill, Howard S Hochster, Michel Ducreux, Dirk Arnold, Varsha Sundaresan, Siddha Kasar, Adela Pina, Ziji Yu, William R Schelman, Lucy Chen, Josep Tabernero. Early carcinoembryonic antigen (CEA) dynamics to predict the efficacy of fruquintinib (F) + best supportive care (BSC) in patients with metastatic colorectal cancer (mCRC) enrolled in FRESCO-2 abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6408.
# Background Patients with chronic lung disease (CLD), such as asthma or chronic obstructive pulmonary disease, were expected to have an increased risk of clinical manifestations and severity of ...COVID-19. However, these comorbidities have been reported less frequently than expected. Chronic treatment with inhaled corticosteroids (ICS) may impact the clinical course of COVID-19. The main objective of this study is to know the influence of chronic treatment with ICS on the prognosis of COVID-19 hospitalized patients with CLD. # Methods A multicenter retrospective cohort study was designed, including patients hospitalized with COVID-19. Epidemiological and clinical data were collected at admission and at seven days, and clinical outcomes were collected. Patients with CLD with and without chronic treatment with ICS were compared. # Results Two thousand five hundred ninety-eight patients were included, of which 1,171 patients had a diagnosis of asthma and 1,427 of COPD (53.37% and 41.41% with ICS, respectively). No differences were found in mortality, transfer to ICU, or development of moderate-severe ARDS. Patients with chronic ICS had a longer hospital stay in both asthma and COPD patients (9 vs. 8 days, *p =* 0.031 in asthma patients), (11 vs. 9 days, *p =* 0.018 in COPD patients); although they also had more comorbidity burden. # Conclusions Patients with chronic inhaled corticosteroids had longer hospital stays and more chronic comorbidities, measured by the Charlson comorbidity index, but they did not have more severe disease at admission, evaluated with qSOFA and PSI scores. Chronic treatment with inhaled corticosteroids had no influence on the prognosis of patients with chronic lung disease and COVID-19.
Este artículo analiza el papel de las matemáticas en la formación de los ingenieros. Tradicionalmente las matemáticas se enseñaban de manera muy subjetiva y los alumnos solo aprendían símbolos, ...formas o signos que para ellos no representaban nada y lo que hacían era aprendérselos de memoria por la importancia que tenían para sus profesores, pero en realidad ellos no comprendían, por lo que se hacía más difícil su aprendizaje y no tuviesen una mejor preparación para la vida. Se trata es de que el Individuo vaya aceptando la realidad de que en el mundo en que se desenvuelve, las matemáticas son algo esencial en el desarrollo de su carrera y se le proporciona al estudiante los conocimientos matemáticos necesarios para la compresión de varios problemas relacionados con la ingeniería.
Background
Emerging evidence suggests that myeloid cells play a critical role in glioblastoma (GBM) immunosuppression. Disappointing results of recent checkpoint inhibitor trials suggest that ...combination immunotherapy with alternative agents could be fruitful in overcoming immunosuppression. Overexpression of chemokine receptor CXCR4 is associated with poor prognosis in GBM. We investigate the treatment effects of combination immunotherapy with anti-PD-1 and anti-CXCR4 in a murine glioma model.
Methods
C57BL/6 mice were implanted with GL261-Luc+ glioma cells and randomized into 4 arms: (1) control (2) anti-PD-1 (3) anti-CXCR4, and (4) anti-PD-1 and anti-CXCR4 therapy. Overall survival and median survival were assessed. Cell populations were assessed by flow cytometry.
Results
Combination therapy conferred a significant survival benefit compared to control and monotherapy arms. Mice that received combination therapy demonstrated immune memory and decreased populations of immunosuppressive tumor-infiltrating leukocytes, such as monocytic myeloid-derived suppressor cells and microglia within the brain. Furthermore, combination therapy improved CD4+/CD8+ ratios in the brain as well as contributed to increased levels of pro-inflammatory cytokines.
Conclusions
Anti-CXCR4 and anti-PD-1 combination immunotherapy modulates tumor-infiltrating populations of the glioma microenvironment. Targeting myeloid cells with anti-CXCR4 facilitates anti-PD-1 to promote an antitumor immune response and improved survival rates.
Polymeric ionic liquids (PILs) have triggered great interest as all solid-state flexible electrolytes because of safety and superior thermal, chemical, and electrochemical stability. It is of great ...importance to fabricate highly conductive electrolyte membranes capable to operate above 120 °C under anhydrous conditions and in the absence of mineral acids, without sacrificing the mechanical behavior. Herein, the diminished dimensional and mechanical stability of poly1-(3H-imidazolium)ethylenebis(trifluoromethanesulfonyl)imide has been improved thanks to its infiltration on a polybenzimidale (PBI) support with specific pore architecture. Our innovative solution is based on the synergic combination of an emerging class of materials and sustainable large-scale manufacturing techniques (UV polymerization and replication by microtransfer-molding). Following this approach, the PIL plays the proton conduction role, and the PBI microsieve (SPBI) mainly provides the mechanical reinforcement. Among the resulting electrolyte membranes, conductivity values above 50 mS·cm–1 at 200 °C and 10.0 MPa as tensile stress are shown by straight microchannels of poly1-(3H-imidazolium)ethylenebis(trifluoromethanesulfonyl)imide cross-linked with 1% of dyvinylbenzene embedded in a PBI microsieve with well-defined porosity (36%) and pore diameter (17 μm).
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