BACKGROUND Airway management in tracheostomized patients may become particularly challenging in the presence of recent stomas, local infection, single-lung ventilation, and restricted intraoperative airway access. False passage ventilation is an uncommon but potentially catastrophic complication requiring immediate recognition and rescue. CASE REPORT We report the case of a 63-year-old man with a recent surgical tracheostomy performed after emergent cricothyrotomy for upper airway obstruction secondary to cervical cellulitis with mediastinal extension. The patient underwent urgent thoracotomy for mediastinal debridement under general anesthesia with single-lung ventilation achieved using a bronchial blocker through the existing tracheostomy tube. During surgery in the lateral decubitus position, abrupt loss of capnography and inability to ventilate occurred. Bronchoscopic evaluation demonstrated tracheostomy tube malposition with false passage ventilation associated with peristomal tissue dehiscence and severe local infection. In this context, the combination of single-lung ventilation, lateral decubitus positioning, and limited access to the tracheostomy created a particularly challenging intraoperative airway rescue scenario. Given the need for immediate restoration of oxygenation, emergency orotracheal intubation using videolaryngoscopy was successfully performed without prior supination, allowing rapid recovery of ventilation and completion of the procedure. CONCLUSIONS This case highlights the diagnostic and rescue challenges posed by false passage ventilation during thoracic surgery in recently tracheostomized patients. It reinforces the importance of early recognition of airway loss and prioritization of oxygenation-restoring rescue strategies in similar high-risk intraoperative settings. This report also underscores the vulnerability of recently created and infected tracheostomies during complex thoracic procedures requiring single-lung ventilation.

Respiratory cultures before and after lung transplantation are frequently obtained but often difficult to interpret. A positive culture may represent donor-derived organisms, recipient reservoir recolonization, hospital acquisition, transient colonization, invasive infection, or a marker of evolving graft vulnerability. This review summarizes how respiratory microbiology changes across the lung transplant timeline and proposes a practical framework for clinical interpretation. Conventional culture-based studies and recent airway microbiome literature are integrated to examine donor-recipient attribution, pre-transplant colonization, disease-specific reservoirs, single-lung transplantation, and pathogen-specific risk. Pre-transplant recipient colonization, particularly with multidrug-resistant gram-negative organisms, appears more consistently associated with early post-transplant pneumonia and short-term outcomes than donor culture positivity alone when targeted antimicrobial therapy is used. Disease-specific patterns are also important: cystic fibrosis and bronchiectasis favor recolonization from persistent reservoirs, whereas single-lung transplantation creates a dual-airway ecosystem in which the native lung may remain microbiologically relevant. Persistent or recurrent isolation of organisms such as Pseudomonas aeruginosa, Burkholderia cenocepacia, Staphylococcus aureus, Aspergillus species, and nontuberculous mycobacteria should be interpreted in relation to symptoms, imaging, lung function, sampling source, and timing from transplant. Contextual interpretation of respiratory cultures may improve antimicrobial planning, donor acceptance decisions, stewardship, and long-term graft surveillance.

mRNA vaccines have become a clinically validated vaccine platform, as demonstrated by the success of COVID-19 vaccines such as Comirnaty and Spikevax, owing to their rapid design, manufacturing scalability, and capacity to induce in situ antigen expression. A key factor underlying this success is the lipid nanoparticle (LNP) delivery system, which protects mRNA from degradation and promotes efficient cellular uptake and cytoplasmic delivery, thereby enabling the full potential of mRNA technology. The continued advancement of mRNA-LNP vaccines requires integrated optimization of mRNA design, LNP composition, and delivery strategies to achieve improved stability, efficient intracellular delivery, and balanced immune responses. Despite remarkable progress, challenges related to formulation stability, long-term storage stability, safety and reactogenicity concerns, and durability of immune protection continue to hinder the broader application of mRNA-LNP vaccine platforms. This review provides an integrated overview of recent advances in mRNA-LNP vaccines, covering mRNA molecular engineering, LNP composition and delivery mechanisms, immune responses, clinical progress, and current developmental challenges. Furthermore, emerging strategies, including thermostable formulations, next-generation LNPs with improved targeting capability, emerging RNA platforms, and artificial intelligence-assisted optimization of RNA sequences and lipid materials, are discussed. By summarizing current achievements and future opportunities, this review highlights key principles guiding the rational design of safer, more stable, and more precise mRNA-LNP vaccine platforms and provides insights into accelerating their clinical translation.

Chlamydia felis is a primary cause of feline conjunctivitis and upper respiratory tract disease. Detection of C. felis largely relies on molecular tests; however, these tests cannot assess prior exposure or herd immunity. In China, no standardized commercial serologic assay for C. felis is available. We developed an indirect ELISA based on the major outer membrane protein (MOMP) of a locally isolated C. felis strain (GXNN36). A truncated ompA gene (encoding MOMP, amino acids 22-392, which retains the major antigenic domains, including the 4 variable domains VD1-4) was expressed in Escherichia coli, and the recombinant protein was purified. After optimizing reaction conditions, the iELISA had high specificity (no cross-reactivity with feline calicivirus, panleukopenia virus, or feline coronavirus), high sensitivity (detection limit up to 1:20,480 dilution), and good reproducibility (intra- and inter-assay CVs <10%). The cutoff optical density (OD450) was 0.630. Assessment against western blotting using 20 clinical sera had 95% concordance. Testing of 144 feline serum samples from Guangxi, China revealed a seroprevalence of 20.1%. Our MOMP-based iELISA using a Chinese C. felis isolate offers a practical and regionally relevant tool for serosurveillance.

In the current era of cystic fibrosis (CF) transmembrane conductance regulator (CFTR)-directed therapies (modulators), people with CF have significant improvement in pulmonary disease burden and overall survival. Extrapulmonary complications, including those affecting the gastrointestinal and renal systems, are gaining attention. Nephrolithiasis is increasingly recognized as a significant comorbidity in CF. The mechanisms underlying nephrolithiasis in CF are multifactorial and closely associated with altered gastrointestinal milieu in CF. Overt or residual fat malabsorption (due to exocrine pancreatic insufficiency along with other causes such as altered bile salt handling, acidic intestinal pH), and increased intestinal permeability collectively enhance enteric oxalate absorption. Renal stones in CF tend to present at a younger age, are associated with higher recurrence rates, and require more frequent procedural interventions compared with the general population with nephrolithiasis. With the increased survival in the post modulator era, the burden of renal complications in CF is expected to grow. There is lack of CF-specific nephrolithiasis guidelines and more studies on this topic are needed. Also, given the paucity of pediatric studies, literature from adults can be carefully inferred. Clinicians should educate people with CF on preventative strategies such as optimizing pancreatic enzyme replacement therapy, enhancing hydration, nutritional management strategies such as optimizing dietary calcium intake particularly when consuming high-oxalate foods, managing hypocitraturia, and minimization of nephrotoxic medication exposures. Multidisciplinary team approach is recommended to optimize outcomes from nephrolithiasis. In this review, the epidemiology, pathogenic mechanisms, and clinical management of nephrolithiasis in CF, with an emphasis on early-life contributors and opportunities for improved prevention in CF management are detailed.

Mycoplasma pneumoniae infection (MPI) can lead to extrapulmonary diseases, in which diarrhea occurs frequently. The role and impact of microRNA-95 (miR-95) in MPI and MPI with diarrhea (MPI+DIA) remain elusive. The aim of the study is to investigate miR-95 expression and its functional impact in paediatric MPI with diarrhea.

The study enrolled 80 MPI patients (53 without diarrhea, 27 with diarrhea) and 80 matched healthy controls. Expression of miR-95 was quantified using reverse transcription quantitative polymerase chain reaction (RT -qPCR). Predictors of disease status were analyzed through binary logistic regression. An in vitro pneumonia model (MP-BEAS-2B) was generated by infecting BEAS-2B cells with Mycoplasma pneumoniae (MP). In parallel, an intestinal epithelial injury model was generated by treating Caco-2 cells with 4 μg/mL lipid-associated membrane proteins (LAMPs). Cell proliferation was measured with cell counting kit-8 (CCK-8), apoptosis by flow cytometry, and interleukin -8 (IL-8) and tumour necrosis factor-alpha (TNF-α) levels were determined via RT-qPCR.

The study revealed that miR-95 was significantly elevated in the MPI group, with a further increase observed in MPI patients complicated with diarrhea. Additionally, miR-95 served as a discriminator among healthy controls, MPI patients, and MPI+DIA patients. In MP-BEAS-2B and LAMPs-Caco-2 cells, miR-95 was highly expressed. However, downregulating miR-95 significantly enhanced cell proliferation, inhibited apoptosis, and reduced the expression of IL-8 and TNF-α.

MiR-95 expression was significantly elevated in MPI patients, and further increased in those with MPI complicated by diarrhea. Downregulating miR-95 significantly protected BEAS-2B and Caco-2 cells from MP damage and alleviated cellular inflammation.

Mycoplasma pneumoniae (MP) infection can lead to various extrapulmonary complications, including myocardial injury (MI). However, the expression levels of ATPase phospholipid transporting 8B1 (ATP8B1) in MP-infected individuals with MI and its potential therapeutic role remain elusive. The aim of the study is to evaluate ATP8B1 as a therapeutic target for MP-induced MI.

The study quantified ATP8B1 expression in patient serum via RT-qPCR and analyzed its diagnostic value for MP and MP+MI using receiver operating characteristic (ROC) curves. Binary logistic regression assessed its association with MP+MI. Serum interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) levels were measured by ELISA and correlated with ATP8B1. In a dual-cell model (MP-infected BEAS-2B cells and AC16 cells exposed to their supernatant), ATP8B1's effects on inflammation, proliferation, reactive oxygen species (ROS), and cardiac injury markers were evaluated via RT-qPCR, CCK-8, and ELISA.

The study revealed that serum ATP8B1 levels were significantly reduced in the MP group and further decreased in the MP+MI group. ATP8B1 expression levels could distinguish MP patients from MP+MI patients. Serum IL-6 and TNF-α levels were significantly higher in the MP+MI group than in the MP group, and ATP8B1 was negatively correlated with IL-6 and TNF-α. In vitro, ATP8B1 was downregulated in both cell lines. Functionally, over-expression of ATP8B1 effectively attenuated inflammation, ROS production, deficits in cell proliferation, and myocardial injury.

ATP8B1 was expressed lowly in the serum of MP+MI patients. Functional experiments demonstrated that ATP8B1 upregulation significantly attenuated inflammation, ROS generation, proliferation deficits, and myocardial injury.

Acute pulmonary embolism (APE), a life-endangering cardiovascular acute disorder, brings about difficulties in early diagnosis. The aim of the study is to investigate the expression of miR-218-5p, its clinical significance, and mechanism in APE.

A total of 102 APE patients and 98 healthy controls were recruited, with miR-218-5p levels assayed by qRT-PCR; its diagnostic value was assessed by ROC curves. Pearson correlation and multivariate logistic regression analyzed associations with clinical indicators and independent predictive value. Oxygen-glucose deprivation/reoxygenation (OGD/R)-induced human pulmonary artery endothelial cells (HPAECs) were transfected with miR-218-5p mimic to observe the effects on apoptosis, proliferation, inflammation, and oxidative stress. Bioinformatics and dual-luciferase assays validated miR-218-5p targeting CREB1.

Serum miR-218-5p was significantly downregulated in APE (P<0.0001) with high diagnostic efficacy (AUC=0.893). It positively correlated with D-dimer (r=0.759) and Wells scores (r=0.703; P<0.0001) and was an independent APE risk factor (OR=0.053; P<0.0001). In vitro, miR-218-5p overexpression reduced OGD/R-induced HPAEC apoptosis, promoted proliferation, inhibited inflammation (IL-6, IL-1β, TNF-α) and oxidative stress (MDA, ROS), and restored SOD activity (P<0.01). Mechanistically, miR-218-5p directly targeted CREB1 to suppress its expression.

miR-218-5p is downregulated in APE, as a potential diagnostic biomarker. It targets CREB1 to modulate apoptosis, inflammation, and oxidative stress, thereby contributing to APE pathogenesis.

Wildland-urban interface (WUI) wildfires are increasingly important climate-related exposure events because they burn built infrastructure and can mobilize legacy contaminants in addition to generating smoke. Although the acute respiratory effects of wildfire smoke are well described, persistent internal metal mixtures and their association with pulmonary function after WUI disasters remain poorly characterized. Using the August 2023 Maui wildfires as a sentinel model, we evaluated 1,400 adults enrolled 6 to 18 mo after the disaster in a community-engaged cohort. We measured 24 urinary metals and assessed pulmonary function by standardized spirometry at the same visit, enabling paired exposure-response analyses. Compared with US reference levels, participants exhibited elevated internal metal burdens, including antimony (40-fold), manganese (3.8-fold), barium (2.3-fold), and arsenic (2.2-fold), with the highest concentrations clustering in the most affected regions. Across three complementary mixture-modeling approaches, higher cumulative metal burden was consistently associated with greater odds of abnormal spirometry. In weighted quantile sum models, each 1-quantile increase in the positive mixture index, driven primarily by arsenic, cadmium, and copper, was associated with higher odds of FVC, FEV₁, FEV₁/FVC, and FEF_25-75 below the lower limit of normal (odds ratio [OR], 1.71, 1.53, 1.83, and 1.84, respectively). These findings suggest that WUI disasters may generate persistent internal metal mixtures associated with pulmonary impairment months after the event and that air monitoring alone may underestimate the longer-term internal toxic burden following climate-amplified WUI disasters.

Remote patient management (RPM) that supports patient self-monitoring of vital parameters and lifestyle factors may improve cardiovascular risk management (CVRM) in primary care. However, large-scale implementation remains limited, partly due to insufficient evidence on long-term value for money, budget impact, and implications for health care professionals' workload.

This study aimed to estimate the long-term cost-effectiveness, 5-year health care budget impact, and expected changes in general practitioner (GP) and practice nurse (PN) workload associated with the CVRM-Box intervention in the Netherlands.

We conducted a model-based economic evaluation comparing CVRM-Box with care as usual in Dutch primary care integrated CVRM programs. CVRM-Box is a multicomponent RPM intervention comprising a digital blood pressure (BP) monitor, digital weight scale, step counter/activity tracker, and a mobile app, with measurements transferred to the GP practice for periodic review. A time-inhomogeneous cohort Markov model simulated lifetime transitions among health states, including at-risk, post-myocardial infarction (MI), poststroke, recurrent events, cardiovascular death, and noncardiovascular death. Cardiovascular risks were modeled using prediction equations (SCORE2, SCORE2-OP, and SMART2) populated with subgroup-specific risk factor profiles. Intervention effects were modeled as changes in systolic BP derived from a matched cohort study of CVRM-Box. Other key parameters (costs and utilities) were similarly obtained from the matched cohort study, or routine primary care data, and published sources. Outcomes included incremental cost-effectiveness ratios (ICERs, indicating cost per quality-adjusted life year [QALY] gained), cost-effectiveness probabilities, 5-year health care budget impact, and an exploratory workload analysis estimating annual changes in visit time and remote consultation frequency for GPs and PNs. Probabilistic and scenario uncertainty analyses were performed.

In the overall population, CVRM-Box increased costs and QALYs versus care as usual, yielding an ICER of €17,340/QALY gained (EUR €1=US $1.11 as of 29 December 2023) and a 60% probability of cost-effectiveness at a willingness-to-pay threshold of €20,000/QALY. Cost-effectiveness was more favorable in higher-risk subgroups (uncontrolled BP and/or prior MI/stroke), with ≥70% probability of cost-effectiveness at €20,000/QALY, whereas in the lower-risk subgroup with controlled BP and no prior MI/stroke, the intervention is unlikely to be cost-effective (ICER: €42,384/QALY). The 5-year health care budget impact was €2.9 million and €662.2 million for regional and national rollout, respectively. In a typical Dutch primary care practice, the CVRM-Box reduced PN workload by 25.9 h and 44.7 remote consultations annually, while the change in GP workload was negligible (0.5 h; 3.3 remote consultations).

The CVRM-Box multicomponent RPM intervention is likely to be cost-effective among high-risk subgroups but not in lower-risk groups. The intervention further reduces PN workload but not GP workload. Results primarily apply to the Dutch context and may not generalize to health care systems with different payment/incentive arrangements. Additionally, long-term outcomes were modeled using prediction models rather than observed cardiovascular events. Nonetheless, our findings provide an argument for implementation in primary care for higher-risk subgroups.