Predicting responses to omalizumab in antihistamine-refractory chronic urticaria: A real-world longitudinal study.

Background: Treating chronic urticaria (CU) that is unresponsive to H1-antihistamines (H1AHs) is challenging, and the real-world effectiveness of omalizumab remains unclear. Objective: Our aim was to evaluate the real-world effectiveness of omalizumab, optimal response assessment timing, and predictive factors. Methods: Initially, 5535 patients with CU who were receiving at least 20 mg of loratadine daily for at least 6 months (January 2007-August 2021) were screened. Ultimately, 386 patients who had been receiving omalizumab add-on treatment for >6 months were followed-up for more than 2 years. Predictors of treatment response to omalizumab add-on therapy for patients with antihistamine-refractory CU were identified by using a generalized linear model. Results: In our retrospective cohort, omalizumab treatment showed cumulative response rates of 55.2% at 3 months, 71.0% at 6 months, and 81.4% at 9 months for patients with H1AH-refractory CU. Analysis of longitudinal responses to omalizumab treatment revealed 3 distinct clusters: favorable (cluster 1 [n = 158]), intermediate (cluster 2 [n =1 43]), and poor responses (cluster 3 [n = 85]). Subjects were categorized on the basis of whether they had achieved a complete response within 3 months; 213 early responders, 117 late responders, and 56 nonresponders were identified. The initial dose of omalizumab differed significantly among the 3 clusters. Low total IgE level (<40 kU/L) predicted nonresponse (odds ratio [OR] = 3.10 [P = .018]). Early responders were associated with a higher initial omalizumab dose (≥300 mg) (OR = 2.07 [P = .016]), higher basophil counts (OR = 2.0 [P = .014]), total IgE levels exceeding 798 kU/L (OR = 0.37 [P = .047]), and lower platelet-to-lymphocyte ratio (OR = 0.50 [P = .050]). Conclusion: Real-world data reveal 3 distinct clusters for response to omalizumab treatment; confirm low serum total IgE level (<40 kU/L) as a predictor of nonresponse; and identify potential biomarkers, including IgE level, basophil count, and PLR, for early responders.

Relationship of computed tomography-based measurements with symptom perception and quality of life in patients with severe asthma.

BACKGROUND: Symptom perception and quality of life (QOL) are important domains for properly managing severe asthma. This study aimed to assess the relationship between airway structural and parenchymal variables measured using chest computed tomography (CT) and subjective symptom perception and QOL in patients with severe asthma enrolled in the Korean Severe Asthma Registry. METHODS: This study used CT-based objective measurements, including airway wall thickness (WT), hydraulic diameter, functional small airway disease (fSAD), and emphysematous lung (Emph), to assess their association with subjective symptom (cough, dyspnea, wheezing, and sputum) perception measured using the visual analog scale, and QOL measured by the Severe Asthma Questionnaire (SAQ). RESULTS: A total of 94 patients with severe asthma were enrolled in this study. The WT and fSAD% were significantly positively associated with cough and dyspnea, respectively. For QOL, WT and Emph% showed significant negative associations with the SAQ. However, there was no significant association between lung function and symptom perception or between lung function and QOL. CONCLUSION: Overall, WT, fSAD%, and Emph% measured using chest CT were associated with subjective symptom perception and QOL in patients with severe asthma. This study provides a basis for clarifying the clinical correlates of imaging-derived metrics and for understanding the mechanisms of respiratory symptom perception.

SAQ training on sprint, change-of-direction speed, and agility in U-20 female football players.

The purpose of the study was to investigate the effects of an 8-week speed, agility, and quickness (SAQ) training on performance changes in linear sprint speed, change-of-direction (COD) speed, and reactive agility of U-20 female football players. Nineteen female football players randomly served as either experimental (n = 9) or control groups (n = 10). The players were tested for physical fitness tests: linear sprint speed including both short and long distances (5- and 10-m sprints without a ball and 20- and 30-m sprints with and without dribbling), COD speed (arrowhead agility test with and without dribbling a ball, Southeast Missouri [SEMO] agility test, and 22-m repeated slalom dribbling test), and reactive agility. Significant group × time interactions were observed for sprint over long distances and COD speed but not for short sprint and reactive agility performances. Paired t-tests revealed considerable improvements in all performances from the pre-test to post-test for the SAQ group, except for the arrowhead agility (left; p = .07). The control group only exhibited significant improvements in 10-m sprint performance after general football training. Eight weeks of SAQ training were effective at enhancing acceleration, maximum sprint speed, and agility performances amongst highly trained U-20 female football players.

Nanoencapsulation and delivery of bioactive ingredients using zein nanocarriers: approaches, characterization, applications, and perspectives.

Zein has garnered widespread attention as a versatile material for nanosized delivery systems due to its unique self-assembly properties, amphiphilicity, and biocompatibility characteristics. This review provides an overview of current approaches, characterizations, applications, and perspectives of nanoencapsulation and delivery of bioactive ingredients within zein-based nanocarriers. Various nanoencapsulation strategies for bioactive ingredients using various types of zein-based nanocarrier structures, including nanoparticles, nanofibers, nanoemulsions, and nanogels, are discussed in detail. Factors affecting the stability of zein nanocarriers and characterization methods of bioactive-loaded zein nanocarrier structures are highlighted. Additionally, current applications of zein nanocarriers loaded with bioactive ingredients are summarized. This review will serve as a guide for the selection of appropriate nanoencapsulation techniques within zein nanocarriers and a comprehensive understanding of zein-based nanocarriers for specific applications in the food, pharmaceutical, cosmetic, and agricultural industries. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01489-6.

Diagnostic biomarkers for chronic rhinosinusitis in adult asthmatics in real-world practice.

Background: Chronic rhinosinusitis (CRS) is a common comorbid condition of asthma that affects the long-term outcome of asthmatic patients. CRS is a heterogeneous disease requiring multiple biomarkers to explain its pathogenesis. This study aimed to develop potential biomarkers for predicting CRS in adult asthmatic patients in a real-world clinical setting. Methods: This study enrolled 108 adult asthmatic patients who had maintained anti-asthmatic medications, including medium-to-high doses of inhaled corticosteroid plus long-acting ß2-agonists, and compared clinical characteristics between patients with CRS (CRS group) and those without CRS (non-CRS group). CRS was diagnosed based on the results of paranasal sinus X-ray and/or osteomeatal-unit CT as well as clinical symptoms. Type-2 parameters, including blood eosinophil count, serum levels of periostin/dipeptidyl peptidase 10 (DPP10) and clinical parameters, such as FEV1% and fractional exhaled nitric oxide (FeNO), were analyzed. All biomarkers were evaluated by logistic regression and classification/regression tree (CRT) analyses. Results: The CRS group had higher blood eosinophil counts/FeNO levels and prevalence of aspirin-exacerbated respiratory disease (AERD) than the non-CRS group (n = 57, 52.8% vs. n = 75, 47.2%; P < 0.05), but no differences in sex/smoking status or asthma control status were noted. The CRS group had higher serum periostin/DPP10 levels than the non-CRS group. Moreover, logistic regression demonstrated that serum periostin/DPP10 and the AERD phenotype were significant factors for predicting CRS in asthmatic patients (adjusted odds ratio, 2.14/1.94/12.39). A diagnostic algorithm and the optimal cutoff values determined by CRT analysis were able to predict CRS with 86.27% sensitivity (a 0.17 negative likelihood ratio). Conclusion: Serum periostin, DPP10 and the phenotype of AERD are valuable biomarkers for predicting CRS in adult asthmatic patients in clinical practice.

Real-world treatment trajectories of adults with newly diagnosed asthma or COPD.

BACKGROUND: There is a lack of knowledge on how patients with asthma or chronic obstructive pulmonary disease (COPD) are globally treated in the real world, especially with regard to the initial pharmacological treatment of newly diagnosed patients and the different treatment trajectories. This knowledge is important to monitor and improve clinical practice. METHODS: This retrospective cohort study aims to characterise treatments using data from four claims (drug dispensing) and four electronic health record (EHR; drug prescriptions) databases across six countries and three continents, encompassing 1.3 million patients with asthma or COPD. We analysed treatment trajectories at drug class level from first diagnosis and visualised these in sunburst plots. RESULTS: In four countries (USA, UK, Spain and the Netherlands), most adults with asthma initiate treatment with short-acting ß2 agonists monotherapy (20.8%-47.4% of first-line treatments). For COPD, the most frequent first-line treatment varies by country. The largest percentages of untreated patients (for asthma and COPD) were found in claims databases (14.5%-33.2% for asthma and 27.0%-52.2% for COPD) from the USA as compared with EHR databases (6.9%-15.2% for asthma and 4.4%-17.5% for COPD) from European countries. The treatment trajectories showed step-up as well as step-down in treatments. CONCLUSION: Real-world data from claims and EHRs indicate that first-line treatments of asthma and COPD vary widely across countries. We found evidence of a stepwise approach in the pharmacological treatment of asthma and COPD, suggesting that treatments may be tailored to patients' needs.

The LKB1-TSSK1B axis controls YAP phosphorylation to regulate the Hippo-YAP pathway.

The Hippo pathway's main effector, Yes-associated protein (YAP), plays a crucial role in tumorigenesis as a transcriptional coactivator. YAP's phosphorylation by core upstream components of the Hippo pathway, such as mammalian Ste20 kinase 1/2 (MST1/2), mitogen-activated protein kinase kinase kinase kinases (MAP4Ks), and their substrate, large tumor suppressor 1/2 (LATS1/2), influences YAP's subcellular localization, stability, and transcriptional activity. However, recent research suggests the existence of alternative pathways that phosphorylate YAP, independent of these core upstream Hippo pathway components, raising questions about additional means to inactivate YAP. In this study, we present evidence demonstrating that TSSK1B, a calcium/calmodulin-dependent protein kinase (CAMK) superfamily member, is a negative regulator of YAP, suppressing cellular proliferation and oncogenic transformation. Mechanistically, TSSK1B inhibits YAP through two distinct pathways. Firstly, the LKB1-TSSK1B axis directly phosphorylates YAP at Ser94, inhibiting the YAP-TEAD complex's formation and suppressing its target genes' expression. Secondly, the TSSK1B-LATS1/2 axis inhibits YAP via phosphorylation at Ser127. Our findings reveal the involvement of TSSK1B-mediated molecular mechanisms in the Hippo-YAP pathway, emphasizing the importance of multilevel regulation in critical cellular decision-making processes.

The KAAACI Guidelines for Sublingual Immunotherapy.

Allergen immunotherapy is regarded as the only disease-modifying treatment option for various allergic conditions, including allergic rhinitis and asthma. Among the routes of administration of allergens, sublingual immunotherapy (SLIT) has gained clinical interest recently, and the prescription of SLIT is increasing among patients with allergies. After 30 years of SLIT use, numerous pieces of evidence supporting its efficacy, safety, and mechanism allows SLIT to be considered as an alternative option to subcutaneous immunotherapy. Based on the progressive development of SLIT, the current guideline from the Korean Academy of Asthma, Allergy, and Clinical Immunology aims to provide an expert opinion by allergy, pediatrics, and otorhinolaryngology specialists with an extensive literature review. This guideline addresses the use of SLIT, including 1) mechanisms of action, 2) appropriate patient selection for SLIT, 3) the currently available SLIT products in Korea, and 4) updated information on its efficacy and safety. This guideline will facilitate a better understanding of practical considerations for SLIT.

Real-World Effectiveness of Statin Therapy in Adult Asthma.

BACKGROUND: Blood lipids affect airway inflammation in asthma. Although several studies have suggested anti-inflammatory effects of statins on asthmatic airways, further studies are needed to clarify the long-term effectiveness of statins on asthma control and whether they are an effective treatment option. OBJECTIVE: To evaluate the long-term effectiveness of statins in the chronic management of adult asthma in real-world practice. METHODS: Electronic medical record data spanning 28 years, collected from the Ajou University Medical Center in Korea, were used to conduct a retrospective study. Clinical outcomes were compared between patients with asthma who had maintained statin use (the statin group) and those not taking statins, whose blood lipid tests were always normal (the non-statin group). We performed propensity score matching and calculated hazard ratios with 95% CIs using the Cox proportional hazards model. Severe asthma exacerbation was the primary outcome; asthma exacerbation, asthma-related hospitalization, and new-onset type 2 diabetes mellitus and hypertension were secondary outcomes. RESULTS: After 1:1 propensity score matching, the statin and non-statin groups each included 545 adult patients with asthma. The risk of severe asthma exacerbations and asthma exacerbations was significantly lower in the statin group than in the non-statin group (hazard ratios [95% CI] = 0.57 [0.35-0.90] and 0.71 [0.52-0.96], respectively). There were no significant differences in the risk of asthma-related hospitalization or new-onset type 2 diabetes mellitus or hypertension between groups (0.76 [0.53-1.09], 2.33 [0.94-6.59], and 1.71 [0.95-3.17], respectively). CONCLUSION: Statin use is associated with a lower risk of asthma exacerbation, with better clinical outcomes in adult asthma.

KAAACI Guidelines for Allergen Immunotherapy.

Allergen immunotherapy (AIT) is a causative treatment for various allergic diseases such as allergic rhinitis, allergic asthma, and bee venom allergy that induces tolerance to offending allergens. The need for uniform practice guidelines in AIT is continuously growing because of the increasing discovery of potential candidates for AIT and evolving interest in new therapeutic approaches. This guideline is an updated version of the Korean Academy of Asthma Allergy and Clinical Immunology recommendations for AIT published in 2010. This updated guideline proposes an expert opinion by allergy, pediatrics, and otorhinolaryngology specialists with an extensive literature review. The guideline deals with basic knowledge and methodological aspects of AIT, including mechanisms, clinical efficacy, patient selection, allergens extract selection, schedule and doses, management of adverse reactions, efficacy measurements, and special consideration in pediatrics. The guidelines for sublingual immunotherapy will be covered in detail in a separate article.

Long-term efficacy of anti-IL-4 receptor antibody in a patient with aspirin-exacerbated respiratory disease and IgG4-related disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) and IgG4-related disease (IgG4RD) share a common pathway of Th2-mediated immune mechanism; there have been several cases of IgG4RD developed in patients with asthma, especially in those comorbid with chronic rhinosinusitis (CRS). IgG4RD has often been treated with systemic corticosteroids, rituximab, or immune-suppressive agents, but frequently failed with relapse. CASE PRESENTATION: Here, we present a case of a 64-year-old male patient with severe AERD with CRS complicated with IgG4RD, who has been successfully treated and maintained with anti-IL-4 receptor antibody, dupilumab after achieving unsatisfactory responses with previous treatments including steroids, rituximab, omalizumab, and reslizumab. The patient's symptoms (periorbital swelling and asthmatic/nasal symptoms) were remarkably improved; serum levels of IgG4/IgE as well as plasmablast/eosinophil counts progressively decreased without any recurrence sign for over 2 years of dupilumab treatment. CONCLUSION: These findings demonstrate that blocking the IL-4/IL-13 pathway with dupilumab can be an effective treatment with long-term safety in patients with severe AERD with CRS complicated by IgG4RD.

Long-term clinical outcomes of aspirin-exacerbated respiratory disease: Real-world data from an adult asthma cohort.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is a phenotype of severe asthma, but its disease course has not been well documented compared with that of aspirin-tolerant asthma (ATA). OBJECTIVES: This study aimed to investigate the long-term clinical outcomes between AERD and ATA. METHODS: AERD patients were identified by the diagnostic code and positive bronchoprovocation test in a real-world database. Longitudinal changes in lung function, blood eosinophil/neutrophil counts, and annual numbers of severe asthma exacerbations (AEx) were compared between the AERD and the ATA groups. Within a year after baseline, two or more severe AEx events indicated severe AERD, whereas less than two AEx events indicated nonsevere AERD. RESULTS: Among asthmatics, 353 had AERD in which 166 and 187 patients had severe and nonsevere AERD, respectively, and 717 had ATA. AERD patients had significantly lower FEV1%, higher blood neutrophil counts, and higher sputum eosinophils (%) (all p < .05) as well as higher levels of urinary LTE4 and serum periostin, and lower levels of serum myeloperoxidase and surfactant protein D (all p < .01) than those with ATA. In a 10-year follow-up, the severe AERD group maintained lower FEV1% with more severe AEs than the nonsevere AERD group. CONCLUSION AND CLINICAL RELEVANCE: We demonstrated that AERD patients presented poorer long-term clinical outcomes than ATA patients in real-world data analyses.

Purification methods to reduce interference by dextran sodium sulfate with quantification of gene expression in intestinal tissue samples from a piglet model of colitis.

Dextran sodium sulfate (DSS) is commonly used to induce intestinal (i.e., colonic) inflammation in a variety of animal models. However, DSS is known to cause interference when using quantitative-real time polymerase chain reaction (qRT-PCR) methods, thereby invalidating accurate and precise measurement of tissue gene expression. Therefore, the goal of this study was to determine whether different mRNA purification methods would reduce DSS-interference. Colonic tissue samples were collected at postnatal days (PND) 27 or 28 from pigs that had not been administered DSS (Control), and two independent groups of pigs that received 1.25 g of DSS/kg of BW/d (DSS-1 and DSS-2) from PND 14 to 18. Tissue samples collected were subsequently stratified into three purification methods (i.e., 9 total treatment × method combinations), including: 1) no purification, 2) purification with lithium chloride (LiCl), or 3) purification using spin column filtration. All data were analyzed using a one-way ANOVA in the Mixed procedure of SAS. The average RNA concentrations across all treatments were between 1,300 and 1,800 µg/µL for all three in vivo groups. Although there were statistical differences among purification methods, the 260/280 and 260/230 ratios fell between acceptable limits of 2.0 to 2.1 and 2.0 to 2.2, respectively, for all treatment groups. This confirms the RNA quality was adequate and not influenced by purification method in addition to suggesting the absence of phenol, salts, and carbohydrate contamination. For pigs in the Control group that did not receive DSS, qRT-PCR Ct values of four cytokines were achieved, though these values were not altered by purification method. For pigs that had undergone DSS dosing, those tissues subjected to either no purification or purification using LiCl did not generate applicable Ct values. However, when tissues derive from DSS-treated pigs underwent spin column purification, half of the samples from DSS-1 and DSS-2 groups generated appropriate Ct estimates. Therefore, spin column purification appeared to be more effective than LiCl purification, but no method was 100% effective, so caution should be exercised when interpreting gene expression results from studies where animals are exposed to DSS-induced colitis.

Dextran sodium sulfate (DSS) is a chemical used to experimentally induce colonic inflammation in animal models. However, DSS causes chemical inhibition of processes involved with quantitative real-time polymerization chain reaction, thereby inhibiting the measurement of gene expression in tissues. In this study, differing methods of RNA purification were applied to remove DSS inhibition. Because no purification methods were 100% effective in alleviating this interference, caution should be exercised when interpreting gene expression results from studies where animals are exposed to DSS-induced colitis.

A nozzle simulation chip toward high-throughput formation of curcumin-loaded zein nanoparticles with tunable properties.

Size of nanoparticle (NP) is a crucial factor in determining its applicability to various fields. This study aimed to develop a nozzle chip for the scalable formation of self-assembled curcumin-loaded zein NPs with tunable properties. A four-factor (zein concentration in dispersed phase, ethanol concentration in continuous phase, flow rate ratio, and total flow rate), three-level Box-Behnken design on the measured responses (particle size and polydispersity index [PDI]) was established. The particle size and PDI, ranging from 194.43 to 420.51 nm, and 0.089 to 0.219, respectively, were readily controlled by adjusting four factors. Under the optimal conditions of 6% zein, 0% EtOH, the flow rate ratio of 7, and a total flow rate of 8 mL/min targeting higher production rate, the particle size of 306.02 ± 1.52 nm (mean ± standard deviation) and the PDI of 0.135 ± 0.001 were obtained. High throughput for zein NP production (86.4 g/day) was reached, which was 200 and 960 times higher than using microfluidic and electrospraying techniques, respectively. Curcumin-loaded zein NPs under the abovementioned experimental conditions were successfully prepared via the nozzle chip with the encapsulation efficiency of 64.29% ± 0.29%, a loading capacity of 3.06% ± 0.01%, enhanced stability, and improved in vitro antioxidant properties. Curcumin was primarily released from zein NPs in the simulated intestinal phase. This study demonstrated that the property of self-assembled zein NPs can be tuned by altering the operating parameters using the nozzle simulation chip. The results suggest that this approach has potential for use in the food and pharmaceutical industries, particularly for curcumin encapsulation. PRACTICAL APPLICATION: The fabricated nozzle chip is a promising technology to obtain zein nanoparticles (NPs) with enhanced productivity and narrow particle size distribution. It can be easily adopted to spray drying process. Besides, the nozzle chip shows the potential for the large-scale production of bioactive loaded zein NPs in the food or pharmaceutical industries.

Corrigendum: Clinical implications of atrial fibrillatioN detection using wearabLE devices in patients with cryptogenic stroke (CANDLE-AF) trial: Design and rationale.

[This corrects the article DOI: 10.3389/fcvm.2022.837958.].

Biomarkers for predicting type 2-high and uncontrolled asthma in real-world practice.

BACKGROUND: Blood eosinophil count (BEC), immunoglobulin (Ig) E, and fractional exhaled nitric oxide (FeNO) are key clinical indicators for identifying type 2 (T2) asthma. OBJECTIVE: To provide optimal cutoff points of T2 markers for assessing T2-high or uncontrolled asthma in real-world practice. METHODS: Various clinical and laboratory parameters were analyzed according to the result of T2 markers (BEC, serum-free IgE, and FeNO) in adults with asthma who had maintained antiasthmatic medications. The cutoff levels for representing uncontrolled asthma were determined using receiver operating characteristic analysis. Blood levels of periostin and eosinophil-derived neurotoxin were measured by enzyme-linked immunosorbent assay. Activation markers of circulating eosinophils (Siglec8+) and neutrophils (CD66+) were analyzed by flow cytometry. RESULTS: Of 133 patients with asthma, 23 (17.3%) had 3 T2 markers (BEC ≥ 300 cells/µL, serum-free IgE ≥ 120 ng/mL, and FeNO ≥ 25 parts per billion) and significantly higher levels of sputum eosinophils, blood eosinophil-derived neurotoxin, and Siglec8+ eosinophils but lower 1-second forced expiratory volume percentage, in addition to a higher rate of uncontrolled status (P < .05 for all). Furthermore, patients with uncontrolled asthma had significantly higher levels of FeNO and BEC with lower 1-second forced expiratory volume percentage (P < .05 for all). The optimal cutoff values for predicting uncontrolled asthma were found to be 22 parts per billion of FeNO levels, 161.4 cells/L of BECs, and 85.9 ng/mL of serum-free IgE levels. CONCLUSION: We suggest the optimal cutoff values of BEC, IgE, and FeNO for classifying T2-high or uncontrolled asthma, which could be applied as candidate biomarkers for targeting patients with asthma who require T2 biologics.

A qualitative look at perception and experience of sodium reduction strategies in the food industry through focus groups and individual interviews.

The high incidence of sodium overconsumption in the general population has led sodium reduction in commercial food products to become a topic of importance in the food industry. In order to bridge the gap between sodium reduction understanding in the food industry and academia, focus groups and individual interviews of food industry professionals were conducted. Sodium reduction and influence from external entities such as federal regulations and consumer insight were prominent in the nutritional concerns of food industry professionals. A large variety of sodium reduction strategies were introduced with discussion on the many factors that contribute to their potential for success. Flavor modification methods were most prevalent in the discussion, with particular focus on potassium chloride and incorporating umami taste. Factors that frequently positively contributed to a strategy's success include maintaining functionality and/or important sensory attributes, inexpensive to implement, and being perceived as clean label. Conversely, factors that negatively affect success include adversely impacting flavor, being considered not clean label, and high costs of implementation. Foods important for future sodium reduction varied widely, although those were largely products with high sodium density. Future efforts toward reducing sodium overconsumption and sodium content in the food supply fell into three categories: consumer-focused, industry-focused, and research-focused. Of particular importance for future efforts included greater regulatory pressure and more consumer nutritional education. Findings suggest that future efforts to reduce the incidence of sodium overconsumption should be carried out through multiple avenues rather than focusing on the agency of consumers, the food industry, or research alone.

Effects of Exhaustive Exercise on Inflammatory, Apoptotic, and Antioxidative Signaling Pathways in Human Peripheral Blood Mononuclear Cells.

In the present study, we investigated the effects of exhaustive exercise and recovery on inflammatory, pro-apoptotic, and anti-oxidative responses in human peripheral blood mononuclear cells (PBMCs). Sixteen volunteers participated in a guided physical activity program in which they were subjected to progressive exercise on the treadmill until they were exhausted followed by an 1-hour recovery period. Isolated human PBMCs were collected before exercise, immediately after exercise, and after 1-hour recovery. Exhaustive exercise induced expression of heme oxygenase-1 and glutamate cysteine ligase catalytic subunit and activation of NF-κB and NF-E2 related factor 2 (Nrf2). Apoptosis, as measured by activity and cleavage of caspase-3 and its substrate PARP also significantly increased. However, induction of redox signaling and the pro-apoptotic response fully returned to the baseline level during the 1-hour recovery period. On the other hand, COX-2 expression was continuously elevated after exercise cessation throughout the 1-hour recovery period. Taking all these findings into account, we conclude that exhaustive exercise transiently induces Nrf2-mediated antioxidant gene expression and eliminates damaged cells through apoptosis as part of an adaptive cytoprotective response against oxidative and inflammatory stress.

Roles of real-world evidence in severe asthma treatment: challenges and opportunities.

Recent advances in asthma research have led to the development of novel biologicals that hinder the pathological actions of key molecules in severe asthma. Traditional randomised controlled studies (RCTs), the gold standard for evaluating the efficacy and safety of medical interventions with excellent internal validity, have proven the clinical benefits and favourable safety profiles of type 2 biologicals in severe asthma. However, RCTs are not always ideal because of shortcomings such as limited external validity and practical issues in the management of severe asthma that cannot be solved through strictly designed clinical trials. Thus, the applicability of their findings may be questioned because treatment adherence is frequently poor in the real world. Real-world evidence includes a wide range of real-world data (RWD) collected from multiple sources in clinical practice, such as electronic medical records, healthcare insurance claims and retrospective or prospective patient registries. RWD may help clinicians decide how to manage patients with severe asthma. Real-world evidence is also gaining attention in addressing clinical questions not answered by traditional RCTs. Because there are various types of RWD with different possibilities and limitations, it is important to decide which type of RWD could be "fit for purpose" to address a specific question. This narrative review discusses the challenges and opportunities of RWD for evaluating the effectiveness and clinical outcomes of biological treatments for severe asthma.

Visual classification of pressure injury stages for nurses: A deep learning model applying modern convolutional neural networks.

AIMS: To develop a deep learning model for pressure injury stages classification based on real-world photographs and compare its performance with that of clinical nurses to seek the opportunity of its application in clinical settings. DESIGN: This was a retrospective observational study using a deep learning model. REVIEW METHODS: A plastic surgeon and two wound care nurses labelled a set of pressure injury images. We applied several modern Convolutional Neural Networks architectures and compared the performances with those of clinical nurses. DATA SOURCES: We retrospectively analysed the electronic medical records of hospitalized patients between January 2019 and April 2021. RESULTS: A set of 2464 pressure injury images were compiled and analysed. Using EfficientNet, in classifying pressure injury images, the macro F1-score was calculated to be 0.8941, and the average performance of two experienced nurses was reported as 0.8781. CONCLUSION: A deep learning model for classifying pressure injury images by stages was successfully developed, and the performance of the model was compared with that of experienced nurses. The classification model developed in this study is expected to help less-experienced nurses or those working in under-resourced healthcare settings determine the stages of pressure injury. IMPACT: Our deep learning model can minimize discrepancies in nurses' assessment of classifying pressure injury stages. Follow-up studies on improving the performance of deep learning models using modern techniques and clinical usability will lead to improved quality of care among patients with pressure injury. NO PATIENT OR PUBLIC CONTRIBUTION: Patients or the public were not involved in our research's design, conduct, reporting or dissemination plans because this was a retrospective study that used electronic medical records.