Exercise-induced bronchospasm (EIB) is widely recognized as a common cause of exertional dyspnea. The accurate identification and differentiation of EIB from other causes of exercise intolerance remain challenging in clinical practice. We aimed to analyze CPET-derived ventilatory and metabolic parameters in adolescant athletes with exercise-related dyspnea to assess whether these parameters can aid in differentiating EIB from other non-EIB causes of dyspnea.

This retrospective, observational, cohort study included 47 athletes (8-18 years old) presenting with exercise-related dyspnea. Participants were divided into EIB-positive [EIB (+)] and EIB-negative [EIB (-)] groups based on a ≥10% decrease in forced expiratory volume in 1 second (FEV<inf>1</inf>) after CPET. A control group (N.=36) was also included. Spirometry measurements were obtained before and after CPET, and cardiopulmonary parameters such as peak oxygen uptake (peak VO<inf>2</inf>), oxygen uptake efficiency slope (OUES), and ventilatory equivalents were analyzed.

No significant differences were found between EIB (+) and EIB (-) groups in terms of baseline spirometry values. Post-exercise spirometry revealed significant reductions in FEV<inf>1</inf>, FEV<inf>1</inf>/FVC, FEF<inf>25-75</inf>, and PEF values in the EIB (+) group (P<0.05). Peak VO<inf>2</inf> and peak O<inf>2</inf>/HR were lower in both dyspneic groups compared to controls, but no significant difference was observed between EIB (+) and EIB (-) groups (P>0.05). OUES was moderately correlated with AT VCO<inf>2</inf> (r=0.519) and strongly correlated with peak VO<inf>2</inf> (r=0.804) and peak O<inf>2</inf>/HR (r=0.861).

While EIB affects ventilatory function, athletes with exercise-related dyspnea exhibited similar CPET changes regardless of EIB diagnosis. This suggests that dyspnea in young athletes may not always be due to EIB but could result from other ventilatory adaptations. OUES and peak VO<inf>2</inf> may serve as useful indicators in evaluating dyspnea-related exercise limitations.

To improve the outcomes in patients with tracheoesophageal fistula (TEF), including those with concurrent tracheal stenosis and recurrent fistula, using various modern surgical interventions.

There were 115 patients with TEF in 2004-2023. Annual number of patients doubled when comparing with the period from 1963 to 2002. In 85.4% of cases, TEF was caused by iatrogenic injury of trachea and esophagus after mechanical ventilation or tracheostomy: 56 patients (48.7%) had fistulas after tracheostomy, 42 (36.7%) ones - after intubation. Concurrent TEF and tracheal stenosis were diagnosed in 68 (59.1%) patients. Fistula was more frequently located in the upper segment of the airway (83 (72.2%) patients) and in the larynx (13%). Among 115 patients with TEF, 24 (20.9%) ones previously underwent unsuccessful fistula repair in other clinics. Only 4 (16.7%) ones did not have tracheal stenosis. Twenty-one (30.9%) out of 68 patients with concomitant tracheal stenosis had stridor and underwent emergency endoscopic tracheal recanalization. Balloon dilation was used in only 6 patients, while dilation was used in other cases. Extent of surgical treatment depended on location and size of fistula, as well as its combination with tracheal stenosis. Airway restoration via tracheal resection followed by anastomosis was performed in 29 out of 68 patients with comorbidity. If circumferential tracheal resection was contraindicated, tracheoplasty with T-tube was performed (19 out of 68 patients).

There was no postoperative mortality. Unfavorable postoperative course was diagnosed in 31 (26.9%) patients that comprised 19.3% according to the number of surgeries. Combination of TEF and tracheal stenosis exacerbated the situation. Among 68 similar patients, 21 (30.1%) ones experienced postoperative complications.

The problem of surgical treatment for TEF remains relevant. Basic diagnostic and surgical principles significantly reduced the incidence of postoperative complications and mortality. However, this is less true for TEF with simultaneous tracheal stenosis. These patients constitute the most complex and severe group. Simultaneous surgeries (TEF closure and correction of stenosis via circular tracheal resection with anastomosis) are preferable. In case of TEF recurrence, redo surgeries are possible with favorable results.

Segmented virus genomes, such as those of influenza A viruses (IAVs), consist of multiple segments. This structure enables the generation of novel strains through reassortment, where segments from different strains combine, greatly increasing the genetic diversity of segmented viruses. Reassortment can confer new biological properties to viruses, such as increased transmission rates, as evidenced by several influenza pandemics throughout history. Consequently, it is crucial to monitor reassortment events, particularly emerging ones. The vast availability of viral genome data provides an opportunity to identify emerging reassortment events. However, traditional methods often struggle with scalability due to high computational costs. This study introduces VReassort, a tool for fast and accurate detection of emerging reassortant strains using genome sequences. VReassort leverages deep learning models and phylogenetic-tree-derived features to detect reassortments between segment pairs. Experiments on simulated and real data demonstrate VReassort's superior performance (F1-score $\gt $ 0.8) across diverse scenarios. Remarkably, VReassort analyzed ~1000 IAV strains in under 2 min, achieving speeds over 100 times faster than the benchmark tool. Applying VReassort to large-scale IAV data ($\gt $8000 strains) uncovered intriguing reassortment patterns, while its application to rotavirus data confirmed the feasibility of extending VReassort to other segmented viruses.

COVID-19 infection during pregnancy has been associated with adverse outcomes; however, most investigations were conducted early in the pandemic. The high rates of vaccination in Western Australia during peak transmission present a unique opportunity to reassess the impact of COVID-19 infection in pregnancy.

This study aimed to investigate the impact of COVID-19 infection in pregnancy on adverse obstetric and neonatal outcomes.

The retrospective case-control study conducted at a tertiary centre in Western Australia compared COVID-19 positive and negative pregnancies from March to November 2022. Data from 404 participants (223 positive and 181 negative participants) were analysed. Bivariate and multivariate analyses, adjusted for confounders, were used to assess adverse outcomes.

COVID-19 infection was significantly associated with lower cord blood pH (p = 0.012); but no other adverse obstetric or neonatal outcomes (p > 0.05). Among COVID-19 positive cases, the timing of infection by trimester did not significantly impact adverse outcomes. However, a shorter interval between COVID-19 infection and delivery was associated with higher rates of caesarean sections (p = 0.018) and neonatal comorbidities (p = 0.007). Analysis of COVID-19 severity on outcomes was limited by the small sample size (n = 4).

COVID-19 infection during pregnancy was not associated with clinically significant adverse outcomes, likely influenced by the predominant Omicron strain and high vaccination rates. Limitations of this study included lack of universal screening and a small sample size. Notwithstanding, this study provides valuable insights that reflect the current COVID-19 landscape, underscoring the need for an updated understanding as context surrounding COVID-19 infection evolves.

Community-acquired pneumonia (CAP) poses a serious threat to the lives of adults. Differentially expressed miRNAs play a crucial regulatory role in CAP. This study aims to explore the diagnostic and prognostic significance of miR-4492 in CAP and its possible mechanism of action with tumor necrosis factor receptor-associated factor 6 (TRAF6) in human bronchial epithelial cells (HBEpCs). Differentially expressed miRNAs were screened from the GSE196399 dataset, and miR-4492 levels were collected and detected in the serum of CAP patients. The diagnostic and prognostic value of miR-4492 was evaluated using receiver operating characteristic (ROC) curve, Kaplan-Meier survival analysis, and multivariate Cox regression model. miR-4492-TRAF6 interaction was validated via dual-luciferase assays and Pearson correlation. Cell viability and inflammatory factor concentrations were assessed using the CCK-8 assay and ELISA. miR-4492 was downregulated in the serum of CAP patients. ROC analysis demonstrated that miR-4492 distinguished the CAP patients from healthy controls, and its expression was negatively correlated with the CURB-65 score severity. Low miR-4492 level was a predictor of poor prognosis in CAP. TRAF6 was the target gene of miR-4492. LPS inhibited the expression level of miR-4492 and cell viability, and promoted the expression of TRAF6 and inflammation in HBEpCs. Overexpression of miR-4492 enhanced cell viability and suppressed the inflammatory response of HBEpCs, while overexpression of TRAF6 partly reversed the effect of miR-4492. In conclusion, low serum miR-4492 serves as a diagnostic and prognostic biomarker for CAP. miR-4492 mitigated LPS-induced inflammation and cell damage in HBEpCs by targeting TRAF6.

Since the Covid-19 pandemic entered its endemic phase, France, Italy, and Hungary, as well as many other European countries, have observed a rise in vaccine hesitancy. This study employs a mixed-methods approach to understand the reasons behind this trend by linking statistical observations with in-depth view of vaccine hesitancy. A total of 3,021 adults were surveyed from France, Italy, and Hungary via nationally representative surveys, examining views toward these vaccines. We employed both pooled and un-pooled linear regression analyses. In each country, 20 semi-structured interviews were conducted. Our pooled survey analysis reveals that hesitancy toward Covid-19 and influenza vaccines was higher among respondents reporting mistrust in healthcare providers [95% CI = -0.26,-0.17; P < .001] and lower among those with underlying health conditions. Additionally, older adults were less likely to receive Covid-19 vaccines but more likely to receive an influenza vaccine. Those without a Covid-19 vaccination were 18% points more likely to be unvaccinated against influenza [95% CI = 0.11,0.24; P < .001]. The interviews highlight that these broader patterns reflect a post-pandemic landscape characterised by heightened ambivalence and complexity in vaccine decisions, in which people find it difficult to decide independently and rely more on experts. The interviews also revealed various influences on vaccine hesitancy, including safety concerns, diminished fear of disease, and online misinformation. These indicate that post-pandemic vaccine hesitancy reflects shifting attitudes shaped by shared pandemic experiences across countries, underscoring the need for continued research and monitoring in light of how post-pandemic vaccine hesitancy differs from pre-pandemic forms.

COVID-19 vaccination has significantly reduced mortality and morbidity. Recent studies in unvaccinated people indicate a more complex immune response beyond just the cytokine storm. Understanding changes in the immune cell network is crucial for identifying vaccine-independent immune imbalances, especially in vaccine-naïve patients needing invasive mechanical ventilation (IMV). This knowledge could help improve vaccine development and find biomarkers linked to severe COVID-19.

Peripheral blood immune cells from vaccine-naïve COVID-19 patients from the first pandemic wave were classified into those who required IMV and those who did not (No-IMV). High-dimensional immune phenotyping was performed using multiparametric flow cytometry combined with FlowSOM clustering and UMAP for dimensionality reduction. Additionally, T-cell activation efficiency after polyclonal stimulation was evaluated in vitro.

IMV patients, but not No-IMV, exhibited a marked disruption of immune cell networks, characterized by a loss of immune checkpoint (IC)-expressing T-cell subsets, particularly PD-1- and LAG-3-expressing T cells. Conversely, there was an increase in the frequency of T cells co-expressing molecules linked to inflammatory pathways (TNF/TNFR) and cell death (CD95L). These changes were also associated with reduced CD8⁺ T-cell activation capacity and the rise of non-conventional cytotoxic CD4⁺ T-cell subsets. In the B-cell compartment, IMV patients displayed depletion of CCR7+ subsets and decreased PD-1 expression. Additionally, higher frequencies of NK and NKT cells expressing TNF pathway-related molecules were observed. While classical monocyte subsets expressing ICs such as PD-L1, PD-L2, and TIM-3 remained stable, non-classical monocyte subsets showed altered IC expression. In contrast, No-IMV patients maintained a relatively balanced immune architecture.

Vaccine-naïve COVID-19 patients requiring IMV display an immune landscape distinct from that of No-IMV patients. IMV exhibits a profound imbalance in innate and adaptive immune cell networks, characterized by inflammatory skewing, loss of regulatory subsets, and impaired cytotoxic T-cell functionality, features not observed in No-IMV. These findings reveal coordinated immune alterations beyond cytokine hyperinflammation and identify cellular immune signatures associated with severe COVID-19.

Globally, multiple SARS-CoV-2 vaccines received emergency authorization, primarily based on adenoviral vector, mRNA, or inactivated virus platforms. Among them, Covaxin, an inactivated vaccine, was widely used in India and several Southeast Asian countries. Due to their emergency rollout in 2021, the long-term immunogenicity data to assess the impact of these vaccinations have been limited. This study investigated the prolonged immune responses induced by Covaxin, an inactivated virus-based COVID-19 vaccine, in 250 individuals monitored for 2 years.

This longitudinal study (January 2021-January 2023) tracked 250 participants, collecting blood at seven time points. We measured SARS-CoV-2 spike RBD IgG and neutralizing antibodies using ECLIA and surrogate virus neutralization tests, respectively. We also assessed cellular immunity in a subset of Covaxin recipients through flow cytometry of spike protein-stimulated lymphocytes.

Anti-RBD IgG levels declined rapidly post-vaccination. A significant rise was observed following Omicron infection, with sustained high antibody titers and high virus neutralization capacity. Covaxin recipients demonstrated high CD4⁺ T-cell activity during the Omicron wave, correlating with mild or asymptomatic infections. These findings suggest that Omicron exposure may have served as a natural booster and hold potential for next-generation vaccine development for COVID. Enhanced T-cell responses, particularly after the third dose, further underscored the vaccine's ability to maintain cellular immunity. Compared with Covishield, Covaxin elicited milder immune responses, possibly contributing to its favorable safety profile.

Overall, this study provides one of the first longitudinal analyses of the humoral and T-cell responses to Covaxin, a vaccine widely administered in India and neighboring Southeast Asian countries.

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder. It poses significant challenges in its advanced stages and requires frequent hospitalizations and complex care strategies. The burden on informal caregivers, who play a crucial role in managing the disease, is profound and multifaceted, involving physical, emotional, and social challenges.

This study aimed to explore the lived experiences and needs of primary informal caregivers for patients with advanced COPD in China, with a focus on their emotional, physical, and social challenges and coping strategies.

A phenomenological qualitative approach was employed to provide an in-depth understanding of caregiver experiences. Data were collected through face-to-face semi-structured interviews with 15 primary informal caregivers of advanced COPD patients from Central China. The interviews were analyzed using Colaizzi's method to extract key themes.

Caregivers reported significant emotional burdens, including anxiety and fear related to the patient's health and future. Physical challenges were prevalent, with many caregivers experiencing fatigue and health deterioration due to the demands of caregiving. Social isolation was also a critical issue, as caregiving responsibilities limited personal time and social interactions. Despite these challenges, caregivers employed various coping strategies, though these were often insufficient to fully mitigate the stress of caregiving.

Informal caregivers of patients with advanced COPD often face intense physical and psychological burdens and need comprehensive support systems. Enhancements in caregiver education, the development of targeted psychological supports, and the integration of caregivers into formal care plans are essential to improve the health outcomes of both caregivers and patients.

Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are common comorbidities in intensive care unit (ICU) patients. The albumin-corrected anion gap (ACAG) has shown utility in predicting mortality across various populations; however, its impact on HF patients with COPD remains unclear. This study investigated the relationship between ACAG and mortality in this population.

We conducted a retrospective cohort study using the Medical Information Mart for Intensive Care (MIMIC)-IV database. A total of 1283 patients with heart failure and chronic obstructive pulmonary disease were included from the MIMIC-IV database. ACAG levels were assessed within 24 hours of admission. The association between ACAG and in-hospital and 30-day mortality was analyzed using Kaplan-Meier analysis, multivariate Cox regression, restricted cubic spline (RCS) analysis, subgroup analysis, and receiver operating characteristic (ROC) curve analysis.

Among 1283 HF patients with COPD (54.6% male), in-hospital and 30-day mortality rates were 11.2% and 13.7%, respectively. Kaplan-Meier analysis demonstrated significantly increased mortality risk in patients with higher ACAG levels (log-rank P<0.001). In fully adjusted Cox models, compared to the lowest ACAG group (T1), the highest group (T3) showed hazard ratios of 2.04 (95% CI: 1.18-3.54; p=0.011) for in-hospital mortality and 1.83 (95% CI: 1.12-2.97; p=0.015) for 30-day mortality. RCS analysis revealed a linear relationship between ACAG and mortality risk, consistent across subgroups. ROC analysis demonstrated superior discriminatory ability of ACAG for in-hospital mortality (AUC=0.693) compared to anion gap (AUC=0.571) and albumin (AUC=0.640), with similar findings for 30-day mortality.

ACAG is closely associated with the risk of mortality in HF patients with COPD. It appears to be a potential prognostic predictor for HF patients with COPD, aiding in risk stratification for this population. However, further prospective studies are needed to consolidate our findings.