Management of asymptomatic congenital thoracic malformations (CTMs) remains controversial. Early resection may prevent infection or malignancy and promote compensatory lung growth, but its long-term impact is unclear. This study compared long-term cardiorespiratory and psychosocial outcomes after operative versus conservative management of CTMs and evaluated open versus thoracoscopic surgery.

Children with congenital pulmonary airway malformation, pulmonary sequestration, or congenital lobar emphysema treated at a tertiary center between 2000 and 2023 were identified retrospectively. Operative patients underwent open or thoracoscopic resection, while conservatively managed children were followed radiologically. Prospective follow-up included the 6-minute run, pulmonary function testing, and psychosocial assessment. Propensity score matching adjusted for gestational age, birth weight, lesion extent, prenatal intervention, and associated congenital diaphragmatic hernia.

Among 194 children (median follow-up 8.7 years), 162 underwent surgery and 32 were observed. Surgical patients showed smaller prenatal relative lung volume (51% vs. 79%, p = 0.02) and higher neonatal acuity (ICU admission 78% vs. 54%, p < 0.01). After matching, postnatal length of stay remained longer after surgery (15 vs. 6 days, p = 0.03). Thoracoscopy was associated with shorter postoperative stay, fewer complications and no mortality. Long-term fitness and quality of life were comparable between groups (p > 0.5).

Surgical management of CTMs does not impair long-term exercise capacity or psychosocial outcomes. Minimally invasive resection appears safe and may be offered as a preventive option in asymptomatic patients.

Early initiation of remdesivir (RDV) is recommended to improve COVID-19 outcomes, but real-world studies describing patterns of RDV use and related outcomes among Japanese COVID-19 patients at high-risk of severe outcomes or death are limited. This claims-based cohort study included 60,165 high-risk patients hospitalized with COVID-19 between October 2021 and June 2023 using the DeSC Healthcare claims database. Patients were categorized into early-RDV (within 2 days of hospital admission), late-RDV (between day 3 and day 7), and no-RDV groups based on RDV initiation timing. Descriptive analyses were performed according to RDV groups. Of the study patients, ≥85% were very elderly (≥75 years). Approximately 39% of patients received early RDV, 2% received late RDV, and 59% received no RDV. By day 28, the proportion of alive discharge for early-, late-, and no-RDV groups was 74.9%, 63.1%, and 71.8%, respectively. The mortality for early-, late-, and no-RDV groups was 7.7%, 8.8%, and 8.4%, respectively. Future hypothesis-driven studies with an appropriate adjustment for confounders are needed to formally evaluate the impact of RDV initiation timing on clinical outcomes in this high-risk, predominantly late-elderly population in Japan.

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis in children < 24 months and a major public health concern, causing high rates of Emergency Department (ED) visits, hospitalizations, and Pediatric Intensive Care Unit (PICU) admissions. Nirsevimab is a recombinant monoclonal antibody recommended for all infants and high-risk children < 24 months. A retrospective single-center cohort study was conducted to evaluate the impact of nirsevimab introduction on bronchiolitis epidemiology in an Italian tertiary pediatric ED, accounting for 40,000 admissions/year. All children < 24 months who presented to our ED with bronchiolitis during two consecutive RSV seasons (first season: 1 October 2023 to 30 April 2024; second season: 1 October 2024 to 30 April 2025) were included. Descriptive and multivariate analyses are reported. Overall, 484 patients were analyzed (336 in 2023-2024; 148 in 2024-2025), with immunization coverage reaching 87.5% by April 2025. Compared with the previous season, RSV positivity decreased significantly (32.4% vs. 47.9%; p = 0.003) and was lower in immunized children (16.2% vs. 51.5%; p < 0.001). Immunization was associated with a reduced risk of RSV-positive swab in the second season (OR = 0.159, 95% CI: 0.059-0.397). Among RSV-negative patients, other respiratory viruses increased (p < 0.001), while co-infections increased in RSV-positive cases (p = 0.021). Hospitalization rates remained stable, though absolute admissions were halved. In conclusion, nirsevimab immunization reduced RSV burden, supporting its inclusion in universal prevention programs and the need for multicenter prospective studies to assess long-term outcomes.

Objective: The COVID-19 pandemic has strained healthcare systems and has been associated with substantial morbidity and mortality. Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) enters host cells by binding to angiotensin-converting enzyme 2 (ACE2), implicating dysregulation of the renin-angiotensin system (RAS) in COVID-19 pathophysiology. Measurement of circulating RAS components, including ACE and ACE2, may therefore provide an insight into disease severity and underlying mechanisms. Subjects and Methods: In this retrospective cohort study, 224 adults with PCR-confirmed COVID-19 were stratified by World Health Organization disease-severity criteria into asymptomatic, mild, mild-pneumonia, severe, and critical groups. Plasma ACE and ACE2 concentrations were quantified by ELISA. Demographic, clinical, and laboratory data were extracted from electronic medical records. Results and Conclusions: Increasing disease severity was associated with higher mortality, elevated body mass index, and higher viral load estimates. Severe and critical illness was characterized by leukocytosis with neutrophilia, marked lymphopenia, anemia, elevated inflammatory and coagulation markers, renal dysfunction, and hypoalbuminemia. Plasma ACE2 levels declined progressively with increasing severity and were significantly lower in patients with mild-pneumonia, severe, or critical illness compared with asymptomatic or mild cases, showing a strong inverse correlation with severity. In contrast, plasma ACE levels increased significantly with disease severity. The resulting increase in the ACE/ACE2 ratio indicates a progressive shift toward the pro-inflammatory arm of the RAS, providing mechanistic insight into the COVID-19 pathophysiology.

Background: Respiratory syncytial virus (RSV) is a leading cause of hospitalization for acute respiratory tract infection (ARTI) in young children. Respiratory viral coinfections are frequently identified in RSV-related ARTIs, yet their impact on disease severity remains controversial and may vary according to the co-pathogen involved. In the context of evolving RSV prevention strategies, a clearer understanding of RSV coinfection phenotypes is needed. Methods: We conducted a multicenter retrospective cohort study of children aged ≤ 5 years hospitalized for ARTI at two Italian tertiary-care pediatric hospitals between 1 September 2022 and 30 April 2025. Children with laboratory-confirmed RSV infection detected by multiplex polymerase chain reaction were included. Patients were classified as having RSV monoinfection, RSV-rhinovirus coinfection, or RSV-non-rhinovirus coinfection. Severe disease was defined as a composite outcome including intensive care unit (ICU) admission, need for respiratory or hemodynamic support, or death. Association between infection status and severe disease was evaluated using a Poisson regression model with robust variance, adjusted for age, sex, and comorbidities. Results: Among 231 RSV-related hospitalizations, 118 (51.1%) were classified as RSV monoinfection, 65 (28.1%) as RSV-rhinovirus coinfection, and 48 (20.8%) as RSV-non-rhinovirus coinfection. Children with RSV-rhinovirus coinfection were older and had shorter hospital stays. Severe disease occurred in 80.5% of RSV monoinfections, 70.8% of RSV-rhinovirus coinfections, and 75.0% of RSV-non-rhinovirus coinfections. After adjustment, neither RSV-rhinovirus coinfection (adjusted risk ratio [aRR]: 0.93; 95% confidence interval [95% CI]: 0.80-1.13) nor RSV-non-rhinovirus coinfection (aRR: 0.99; 95% CI: 0.83-1.18) was associated with increased disease severity compared with RSV monoinfection. Conclusions: RSV-rhinovirus and RSV-non-rhinovirus coinfections were not associated with greater disease severity compared with RSV monoinfection in hospitalized children. These findings support pathogen-specific interpretation of multiplex diagnostic results and inform clinical risk stratification in the era of expanding RSV prevention strategies.

Africa reported lower COVID-19-related morbidity and mortality compared to other continents, despite widespread SARS-CoV-2 transmission and limited vaccine access. Proposed immunological explanations include potential pre-existing immunity such as cross-reactive humoral or cellular responses from earlier coronavirus exposures. However, functional immune responses to SARS-CoV-2 in African populations remain poorly characterized. To address this gap, we assessed post-pandemic neutralizing antibody responses against the SARS-CoV-2 D614G variant. We analyzed plasma samples from 989 participants in a cross-sectional survey in Ghana's Eastern and Greater Accra regions. A live virus neutralization assay using Vero E6 TMPRSS2 cells was employed to quantify SARS-CoV-2 D614G-specific neutralizing antibodies. Responses were assessed across collected demographic data. Urban participants exhibited higher median neutralizing antibody titers than rural counterparts, in both vaccinated and unvaccinated groups (p < 0.0001). Among unvaccinated individuals, median neutralizing antibody titers were comparable across age groups in urban settings. Vaccinated individuals showed elevated median titers across all age groups, with urban residents demonstrating stronger responses. Significant sex-based differences in neutralizing titres were also identified. Our findings reveal marked disparities in functional antibody responses between urban and rural populations, likely shaped by differences in SARS-CoV-2 exposure and vaccination. Continued surveillance and immunological profiling remain key for informing vaccine strategies and future pandemic preparedness.

The ongoing panzootic of the highly pathogenic avian influenza (HPAI) H5N1 virus, dominated by clade 2.3.4.4b, constitutes a significant global threat to wildlife, animal health, and public health. Once characterized by sporadic outbreaks, H5N1 has evolved into a sustained, year-round infection with an expanded host range that now includes numerous mammalian species. Its high pathogenicity is primarily driven by the acquisition of a polybasic haemagglutinin cleavage site, enabling systemic viral spread, alongside emerging endothelial and neurotropic properties that contribute to severe disease and high mortality in mammals. Although zoonotic transmission remains limited, H5N1 continues to accumulate mutations associated with mammalian adaptation, particularly within the haemagglutinin and polymerase complex. Notably, recent outbreaks in U.S. dairy cattle highlight the emergence of novel mammalian reservoirs with increased human exposure risk. Concurrently, vaccination strategies are advancing beyond traditional adjuvanted inactivated vaccines toward next-generation platforms, including mRNA and virus-like particle vaccines, designed for rapid deployment and broader immune protection. However, ongoing viral evolution, constrained vaccine availability, and gaps in coordinated surveillance underscore the urgent need for an integrated One Health approach to reduce panzootic risk.

To examine 11-year trends in adverse events (AEs) in a pediatric critical care unit (PCCU), assess the impact of the COVID-19 pandemic on patient safety, and evaluate associations between patient acuity and AE severity.

Retrospective cohort study using interrupted time series analyses and mixed-effects multinomial regression.

A single-center PCCU monitored via the Adverse Event Management System from January 2013 to December 2023.

A total of 7290 critically ill and injured pediatric patients admitted to the PCCU over the study period.

None (observational study). Exposure variables included the COVID-19 pandemic period, invasive mechanical ventilation and noninvasive ventilation.

Demographics, length of stay (LoS), disposition, and AE severity were assessed. The baseline AE rate was 11.94 events per 100 cases. At pandemic onset, AE rates rose by 5.20 events per 100 cases (p = 0.004), then declined 0.81 events per 100 cases quarterly (p = 0.010). Post-pandemic, rates increased 1.94 events per 100 cases quarterly (p = 0.009). LoS decreased 0.01 days quarterly pre-pandemic (p = 0.009), was stable during the pandemic, then increased 0.25 days quarterly post-pandemic (p = 0.033). Higher Pediatric Index of Mortality 2 scores were associated with fewer "near miss" events and more "MinModSev" (minimal, moderate, or severe) AEs. Both mechanical ventilation (p = 0.039) and noninvasive ventilation (p = 0.015) increased the odds of "MinModSev" AEs.

This PCCU experienced a transient increase in AEs during COVID-19, followed by recovery and a post-pandemic rise in both AE rates and LoS. Higher illness severity and respiratory support were associated with more severe AEs. These findings underscore the importance of data-driven monitoring systems to sustain patient safety during and after healthcare crises.

Unravelling the cellular and molecular mechanisms underlying lung injury and repair requires precise spatial context. Profiling cell-to-cell transcriptional variability and spatial orientation has become increasingly sophisticated, but validating results at the protein level still remains challenging, particularly for low-expressed proteins or small-scale samples. Here, we present a workflow established by our group for spatial protein analysis in the lung by combining two commercially available platforms: (1) laser-assisted microdissection (LMD) with (2) a capillary electrophoretic-based immunoassay (CEI). Using this workflow, we demonstrate a simple, accessible, and sensitive method for spatially capturing regions of interest to investigate small-scale samples or low-expressed proteins. This workflow provides an additional option for orthogonal validation for researchers using omics-based approaches. Furthermore, we validated transcriptome analysis results at the protein level by applying this workflow to a pre-clinical model of cigarette smoke (CS)-induced lung injury. In line with the previous findings, the results showed a significant downregulation of the endothelial cell marker in LMD-enriched alveolar regions, suggesting spatial capillary rarefaction, and activation of the mitogen-activated protein kinase (MAPK) signalling pathway in pulmonary vasculature of CS-exposed mice. Our approach overcomes traditional challenges and provides new opportunities for understanding complex disease pathomechanisms and identifying potential therapeutic targets.

Background/Objective: A substantial proportion of infected individuals develop persistent symptoms after the acute phase of COVID-19, regardless of initial disease severity. Long COVID (LC) remains a public health challenge characterized by impaired functional exercise capacity (FEC) and quality of life (QoL). We systematically synthesized evidence on the effects of in-person outpatient pulmonary rehabilitation (OPR) with individualized and supervised exercise in adults with LC. Methods: Following PROSPERO (CRD42023389365), this study reviewed randomized controlled trials (RCTs) and observational cohort studies (OCSs) published between November 2019 and January 2026 in MEDLINE/PubMed, Web of Science, PEDro, and EMBASE. Results: Fifteen studies (n = 803) were included. OPR improved FEC (6MWT; MD: 53.72 m, 95% CI 43.69-63.75) and 30″SST (MD: 4.68, 95% CI 3.59-5.77) and reduced exertional dyspnea. RCTs showed benefits in physical (MD: 8.04, 95% CI 3.02-13.05) and mental QoL (MD: 6.60, 95% CI 2.01-11.18) and dyspnea impact, with inconsistent PF findings. Fatigue showed a trend toward improvement but was measured using heterogeneous patient-reported tools in RCTs and OCSs. Conclusions: Supervised PR improves FEC, QoL, and dyspnea in individuals with LC. In patients with fatigue/PEM, systematic assessment and continuous symptom monitoring are essential. High-quality controlled studies are needed to strengthen evidence and clinical guide.