Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with progressive, irreversible scarring and a median survival of approximately 3-5 years after diagnosis. Current therapies (nintedanib, pirfenidone) modestly slow progression but do not halt or reverse fibrosis, creating a critical therapeutic plateau and unmet need. Improved human-centric models are essential to dissect how genetic susceptibility and chronic epithelial exhaustion drive aberrant repair in IPF. Lung organoids, as three-dimensional (3D) constructs that recapitulate human lung architecture and cellular responses to pathological cues have increasingly been used as important human-relevant platforms for IPF research. In this review, we summarize recent advances in the application of lung organoids to IPF research, including disease modeling, mechanistic studies, and preclinical drug testing, and we discuss the potential and current limitations of patient-derived organoids (PDOs) in personalized medicine. We also outline ongoing efforts to improve these models through the incorporation of vascular, immune, and mechanical components, such as assembloids and lung-on-a-chip systems. Although important challenges remain, including maturation, standardization, and scalability, lung organoids may provide a valuable complementary platform for future IPF research and translational studies.

Post-COVID-19 condition (PCC) is associated with persistent cognitive dysfunction and fatigue, but limited evidence is available regarding long-term outcomes beyond one year.

Longitudinal follow-up assessment.

Patients who had been previously hospitalized or treated in primary care after COVID-19 infection.

Cognitive performance (WAIS-III subtests, Rey Complex Figure, RAVLT, and D2 Test of Attention) and fatigue (MFI-20 and MFS) were examined in 82 participants at 18 months post-infection; 59 of these participants were reassessed at 36 months. Activity limitations were evaluated using structured interviews.

At 18 months, the scores on most cognitive tests were significantly below expected premorbid levels (mean differences: 7-17 T-points). At 36 months, deficits persisted in most domains, with only WAIS Matrices and D2 KL showing modest improvement (Cohen's d: ~0.4). Fatigue remained high across all dimensions of MFI-20, and 75-78% of patients exceeding the mental fatigue cut-off of MFS. Self-reported cognitive impact and activity limitations showed minimal change over time.

Post-COVID-19 cognitive dysfunction and fatigue remain prevalent for up to three years post-infection, particularly affecting attention, processing speed, and working memory. These deficits pose substantial barriers to daily functioning and return to work, highlighting the need for targeted rehabilitation strategies.

Laryngopharyngeal reflux (LPR) is frequently encountered in patients with obstructive sleep apnea (OSA). However, its relationship with OSA severity remains uncertain. Clarifying this association may improve reflux phenotyping and guide otolaryngology-focused evaluation in OSA populations.

To evaluate the association between LPR-related parameters and OSA severity and the relationship between velum obstruction grade and LPR-related measures.

Prospective observational study.

Single tertiary academic medical center (Peking University Third Hospital), outpatient sleep clinic.

A total of 196 adults with polysomnography-diagnosed OSA were enrolled. All completed Reflux Symptom Index (RSI) assessment and laryngoscopic Reflux Finding Score (RFS) evaluation.Intervention or Exposures:No intervention. Exposure was OSA severity classified by the apnea-hypopnea index and velum obstruction grade assessed by the Müller maneuver. Clinically defined LPR was operationally defined as RSI > 13 and/or RFS > 7.

Associations between OSA severity, velum obstruction grade, and LPR-related measures.

Clinically defined LPR was present in 84 of 196 patients with OSA (42.9%). RFS increased significantly with greater OSA severity (P < .001), whereas RSI showed only a nonsignificant increasing trend (P = .070). OSA severity correlated weakly with RSI and more clearly with RFS (r = 0.16, P = .023; r = 0.33, P < .001, respectively). After adjustment for sex, body mass index, and LSO₂, moderate and severe OSA were independently associated with LPR compared with mild OSA (moderate: Odds ratio [OR] = 2.53; 95% Confidence interval [CI]: 1.08-5.95; severe: OR = 4.83; 95% CI: 1.59-14.66). Velum obstruction grade was associated with LPR prevalence and RFS.

Clinically defined LPR was common in adults with OSA and was independently associated with greater OSA severity. RFS appeared to reflect OSA severity more consistently than symptom-based RSI, suggesting that laryngoscopic findings may better capture reflux-related laryngeal involvement in this population.

Laryngoscopic assessment may complement symptom questionnaires and support phenotype-informed evaluation of reflux-related findings in OSA.

3.

Chronic obstructive pulmonary disease (COPD) is the third leading global cause of death, and concurrent sepsis markedly increases short-term mortality, making early identification of high-risk patients clinically essential. This retrospective study, based on the multi-center eICU-CRD database, sought to identify independent predictors of 28-day all-cause mortality and develop a combined prognostic model for intensive care unit (ICU) patients complicated with both COPD and sepsis.

A total of 1814 eligible patients (49.4% male, mean age 70.03 ± 11.20 years) from 208 US ICUs (2014-2015) were included. Baseline demographic, vital, laboratory, blood gas and organ function data within 24 h of admission were collected. Univariate and multivariate Cox regression screened independent prognostic factors, and ROC curves evaluated predictive performance of single markers and the integrated model.

28-day mortality among sepsis-COPD patients was 9.2% (166/1814). After adjusting for confounding variables, the sequential organ failure assessment (SOFA) score was proven to independently affect mortality (HR = 1.19, 95% CI 1.08-1.30, P < 0.001). In contrast, pH (HR = 0.08, 95% CI 0.01-0.96) and body mass index (BMI) (HR = 0.96, 95% CI 0.932-0.998) showed protective effects. All included predictors had area under the curve (AUC) values between 0.57 and 0.67, and the SOFA score achieved the maximum predictive performance. A combined risk model integrating these variables achieved an AUC of 0.70 (95% CI 0.65-0.75, P < 0.001), showing satisfactory discriminatory power. At a threshold value of 0.166 for predictive probability, the model obtained 0.514 sensitivity and 0.791 specificity.

Higher SOFA, lower pH and lower BMI independently predict worse 28-day survival in ICU COPD-sepsis patients. This integrated model exhibits moderate discriminative ability and can serve as an auxiliary tool for rapid risk screening among ICU patients.

This meta-analysis was designed to compare airway complication rates between deep vs. awake laryngeal mask airway (LMA) removal in pediatric non-airway surgery, while discussing the impact of anesthetic agents, patient position and age.

We systematically searched PubMed, Web of Science, and Cochrane Library to identify studies meeting the inclusion criteria. The primary outcome measured was the incidence of overall airway complications, which included laryngospasm, airway obstruction, desaturation, breath-holding, cough, and excessive secretions. Secondary outcomes included subgroup analyses stratified by patient positioning during LMA removal, inhalational anesthetic agents and age.

Pooled analysis of 10 randomized controlled trials (RCTs) (n = 1,713) revealed no significant difference in overall airway complications (relative risk (RR) of 0.93, 95% confidence interval (CI) [0.65-1.32], p = 0.68) or specific outcomes (laryngospasm, desaturation, breath-holding, cough) between deep and awake LMA removal; however, deep removal was associated with a significantly higher airway obstruction risk and a lower incidence of excessive secretions. Subgroup analyses demonstrated that inhalational anesthetic agents type (sevoflurane/isoflurane) did not alter most complications but universally increased airway obstruction risk, whereas positioning during deep removal reduced secretions in both lateral/supine positions yet increased obstruction, with lateral positioning uniquely lowering desaturation risk. Notably, age did not modulate the airway obstruction risk profile: children under 6 years and over 6 years exhibited comparably elevated obstruction risks with deep removal.

This meta-analysis suggests awake LMA removal is associated with lower airway obstruction risk than deep removal, which primarily reduces secretions. Given the higher clinical severity of obstruction, clinicians may prioritize its prevention. This finding appears consistent across age groups, though caution is advised for infants (<2 years) due to limited data. Lateral positioning may mitigate desaturation during deep removal. We suggest risk-stratified protocols, with lateral positioning and monitoring advised if deep removal is performed.

Asthma exhibits pronounced sex differences across the human lifespan, shifting from a predominance in males during childhood toward an increased prevalence, severity, and heterogeneity in females following puberty. These epidemiological patterns are not paralleled by uniform changes in disease phenotype, with adult females exhibiting a higher prevalence of non-type 2 inflammation. Mechanistically, estrogen has emerged as a key regulator of this heterogeneity through its pleiotropic effects on immune and structural cells. However, the immunological actions of estrogen are highly context-dependent, varying with receptor subtype (ERα versus ERβ), hormone concentration, and prevailing inflammatory milieu. Rather than uniformly amplifying immunity, estrogen's principal nuclear receptors exert opposing effects. ERα predominantly promotes immune activation, whereas ERβ exerts counterbalancing anti-inflammatory and bronchoprotective functions. Estrogen promotes immune amplification rather than polarization by simultaneously disrupting regulatory pathways and enhancing T helper 2 (Th2)-, T helper 17 (Th17)-, and innate immune system-mediated responses. Sex chromosome-linked and epigenetic mechanisms, including X-chromosome inactivation escape, further contribute to immune activation in females, although direct evidence in the asthma-specific context remains limited. Importantly, asthma phenotypes are shaped across the female lifespan by interactions between hormonal signaling and other contributing factors such as obesity and other comorbidities, viral infection, and environmental pollutant exposure, as well as emerging non-type 2 pathways including NLRP3 inflammasome activation and neutrophil extracellular trap formation, leading to context-dependent inflammatory patterns. This review summarizes the role of estrogen receptors and various cell types in mediating asthma heterogeneity, providing a mechanistic basis for sex-specific disease variation and highlighting the need for precision strategies that account for hormonal and life-stage differences.

Interstitial lung diseases (ILDs) are a heterogeneous group of diffuse parenchymal lung disorders, including idiopathic interstitial pneumonias, connective-tissue-disease-associated ILD and sarcoidosis. Patients often experience prolonged diagnostic delays and non-specific symptom profiles that overlap with more prevalent conditions. While these delays are well documented, the contribution of low public awareness to these delays is not well described in the Middle East. We aimed to determine the prevalence of ILD awareness in Saudi Arabia and evaluate its independent association with knowledge, attitudes, and care-seeking practices.

We conducted a cross-sectional study of adults (≥18 years) across Saudi Arabia between May and October 2025. The study was reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology guideline (STROBE). Data were collected using a validated knowledge, attitudes, and practices questionnaire, developed with reference to World Health Organisation guidance and the Theory of Planned Behaviour. Factors associated with prior ILD awareness were assessed using multivariable logistic regression. KAP domain scores, Knowledge (0-8), Attitude (1-5), and Practice (1-5) were compared between awareness groups using Mann-Whitney U tests and analysed using multivariable linear regression with standard errors, adjusting for demographics and healthcare background. p Values were adjusted for multiple comparisons using the Benjamini Hochberg false discovery rate procedure. Ethical approval was obtained from King Abdulaziz University.

Of 830 individuals who initiated the survey, 628 (75.7%) provided complete responses and were included in the analysis. Of 628 participants, 116 (18.5%) reported prior ILD awareness. Healthcare providers had 6.45-fold higher odds of awareness (95% CI 3.12-13.32; p < 0.001), and other demographic factors showed no independent association. After adjustment, prior awareness was associated with higher knowledge (β = 3.27, 95% CI 2.77-3.77; p < 0.001) and higher practice scores (p < 0.001). Attitude differences were small and were not statistically significant after full adjustment (p = 0.051). Lack of awareness was reported as a care-seeking barrier by 81% (413/512) of unaware and even by 78% (90/116) of aware participants. Unaware participants prioritised symptom information (65% vs. 53%), whereas aware participants prioritised specialist centre access (53% vs. 43%).

ILD awareness in Saudi Arabia is low (18.5%), concentrated among healthcare providers, with knowledge gaps across both the public and healthcare professionals. The persistence of perceived knowledge deficits, even among those aware demonstrates unmet educational needs. Findings support targeted public campaigns emphasising symptom recognition and primary care education to support earlier recognition, diagnosis, and timely specialist referral.

Antimicrobial resistance in respiratory gram-negative bacilli (GNB) is rising in Saudi Arabia, yet the clinical impact of difficult-to-treat resistance (DTR) remains poorly defined. We characterized temporal trends in organism distribution, non-susceptibility phenotypes, and their association with 30-day in-hospital mortality.

Retrospective cohort of hospitalized patients aged ≥12 years with culture-positive respiratory GNB at a referral hospital in southern Saudi Arabia (January 2013-August 2024). Non-susceptibility phenotypes were fluoroquinolone (FQ-NS), extended-spectrum cephalosporin (ESC-NS), carbapenem non-susceptibility, and DTR. Trends were assessed with segmented binomial regression, mortality with modified Poisson regression.

Among 6,999 isolate-episodes from 3,808 patients, Enterobacterales (57.2%) increased while non-fermenting GNB declined (AAPC, -2.5%). Carbapenem non-susceptibility rose among Enterobacterales (AAPC, + 5.4%), driven by Klebsiella pneumoniae. DTR was 37.6%, rising in Enterobacterales (AAPC, + 12.1%) but declining in Acinetobacter baumannii. Thirty-day mortality was 27.9%. DTR was associated with mortality in Enterobacterales (aRR, 1.34; 95% CI, 1.16-1.55) and non-fermenting GNB (aRR, 1.28; 95% CI, 1.12-1.46); carbapenem non-susceptibility without DTR was not. Mortality rose as active first-line agents decreased (P-trend<.001).

Respiratory GNB epidemiology is shifting toward Enterobacterales with rising resistance. DTR, not carbapenem non-susceptibility alone, was consistently associated with 30-day mortality and provides a meaningful framework for risk stratification and resistance-centered surveillance.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by aberrant wound healing, immune dysregulation, heterogeneous trajectories, and poor prognosis. Only two antifibrotic agents, nintedanib and pirfenidone, are currently approved to slow disease progression, yet inter-individual variability in treatment benefit remains largely unexplained. In IPF, impaired NK-cell activity within the altered lung microenvironment may hinder removal of stressed or senescent cells, promoting fibrosis. The MHC-class I chain-related gene A (MICA) encodes a stress-induced ligand of the NKG2D receptor on NK and CD8⁺ T cells, crucial for immune surveillance.

We analyzed clinical and genetic data from 129 Sardinian IPF patients genotyped for MICA and stratified by antifibrotic therapy (nintedanib, pirfenidone, no therapy, and switchers). Genotypes were assessed in relation to longitudinal lung function, overall survival (OS), and treatment-specific outcomes using multivariate Cox models adjusted for demographic and immunogenetic variables.

MICA-129 genotype frequencies were comparable across treatment groups. In nintedanib-treated patients, the Val/Val genotype was associated with significantly reduced 48-month OS versus Met/Met and Met/Val (p = 0.005). No statistically significant association was observed among pirfenidone-treated patients. After adjustment, Val/Val remained an independent predictor of mortality in the nintedanib group (p = 0.01), irrespective of HLA background.

The MICA-129 Val/Val genotype may represent a candidate immunogenetic marker associated with poorer outcome in nintedanib-treated patients with IPF, underscoring the influence of immune-genetic context on antifibrotic response. Although subgroup sizes limit precision, the consistency and mechanistic plausibility of the association support integrating MICA genotyping into future randomized trials to refine personalized therapeutic strategies in IPF.

Primary aldosteronism (PA) frequently coexists with obstructive sleep apnea (OSA), and this comorbidity is associated with increased cardiometabolic risk. Although both PA and OSA have been individually linked to gut microbiome alterations, it remains unclear which layer of gut microbiome-associated variation best reflects clinical heterogeneity in PA with coexisting OSA.

In this prospective observational study, we performed shotgun metagenomic sequencing and untargeted fecal metabolomic profiling in 29 adults with clinically confirmed PA, who were stratified according to OSA severity (G1-G4) based on overnight polysomnography. Microbial gene richness, taxonomic composition, functional potential based on KEGG annotation, and antibiotic resistance gene profiles were analyzed using standardized bioinformatic workflows. Metabolomic variation was assessed using multivariate analysis, pathway enrichment, and additional exploratory analyses incorporating apnea-hypopnea index (AHI) as a continuous variable. Multiple-testing correction was applied to metabolite-level comparisons.

Global gut microbial gene richness, alpha diversity, beta diversity, and broad functional profiles did not show strong group-level separation across OSA severity strata. Additional analyses using AHI as a continuous variable similarly showed no significant association between AHI and overall gene richness or alpha diversity indices. Nevertheless, selective genera showed exploratory associations with AHI, suggesting that localized taxonomic signals may occur despite relative stability of global community structure. Antibiotic resistance gene profiles showed marked inter-individual variability without clear group-level separation, although ARO richness showed an exploratory inverse association with AHI. In contrast, fecal metabolomic profiling revealed nominal phenotype-associated differences, including trehalose-related metabolites and FAHFA species that showed inverse exploratory associations with AHI. However, no individual metabolite remained significant after global Benjamini-Hochberg false discovery rate correction.

In PA with coexisting OSA, gut microbiome-associated heterogeneity appears to be more readily reflected by selected taxonomic and metabolic signals than by global microbial diversity or broad functional potential. However, given the small sample size, limited control of clinical and lifestyle confounders, and lack of metabolite-level significance after global FDR correction, these findings should be interpreted as exploratory and hypothesis-generating. Larger controlled cohorts incorporating PA subtype, medication exposure, dietary assessment, and longitudinal validation are needed.