Background: Intermediate-high-risk acute pulmonary embolism (APE) presents a clinical challenge, as patients are hemodynamically stable at admission yet carry a substantial risk of deterioration requiring rescue thrombolytic therapy. This study evaluated whether admission complete blood count-derived inflammatory indices, particularly the Systemic Inflammation Response Index (SIRI), are associated with subsequent thrombolytic therapy requirement. Methods: In this retrospective cohort study, 134 patients with computed tomography pulmonary angiography-confirmed intermediate-high-risk APE, classified according to 2019 ESC guidelines, were grouped based on the need for rescue thrombolytic therapy (n = 52) versus no thrombolytic therapy (n = 82). Inflammatory indices were calculated from admission blood samples, and multivariable logistic regression and ROC analyses were performed. Results: Patients requiring thrombolysis had significantly higher SIRI, SII, hs-troponin I, and systolic pulmonary artery pressure (SPAP), and lower lymphocyte counts. In multivariable analysis, SIRI (OR = 2.08, 95% CI 1.37-3.13), SPAP (OR = 1.21, 95% CI 1.06-1.37), and troponin (OR = 1.01 per 10 ng/L increment, 95% CI 1.00-1.01) were independently associated with thrombolytic therapy requirement. Conclusions: SIRI, SPAP, and hs-troponin I were independently associated with thrombolytic therapy requirement in intermediate-high-risk APE. These findings are hypothesis-generating and warrant prospective validation before clinical implementation.
Primary pulmonary artery sarcoma (PPAS) is a mesenchymal tumor originating from the pulmonary artery, accounting for approximately 0.001-0.003% of all sarcomas. The early clinical symptoms are atypical, and diagnosis is often delayed, making the management of this disease challenging. The widespread availability of multidetector computed tomography (MDCT), 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), and high-resolution echocardiography has significantly improved the diagnostic capability for PPAS. We herein report a 74-year-old female patient who presented with a 3-week history of exertional dyspnea without an apparent trigger. She had received anti-inflammatory therapy at another hospital for one week. Five days before admission, she experienced right-sided chest pain without apparent cause, which was respiratory-related. On the day of admission, laboratory tests revealed a slight elevation in D-dimer levels. Echocardiography showed an irregular, moderately echogenic mass at the origin of the right pulmonary artery. Enhanced computed tomography (CT) of the chest revealed a filling defect in the right pulmonary artery accompanied by bilateral pleural effusion. The patient was given heparin anticoagulation therapy. To confirm the nature of these lesions, a PET/CT scan was conducted five days after admission, which indicated hypermetabolism in the right pulmonary artery, suggesting primary pulmonary artery sarcoma. Due to the poor efficacy of anticoagulation therapy, the patient continued to experience breath-holding after physical activity. Subsequently, catheter-guided interventional angiography was carried out for pulmonary artery thrombectomy and biopsy, and histopathological examination revealed pulmonary artery sarcoma. Given the patient's respiratory failure and heart failure, as well as the uncertain efficacy of radiotherapy and chemotherapy, interventional pulmonary artery thrombectomy alleviated the chest pain. Currently, the patient's overall condition is stable.
High-risk pulmonary embolism is characterized by acute onset, rapid progression, and high mortality, underscoring the critical need for establishing an efficient multidisciplinary collaborative rescue system. This article reports the successful management of a 61-year-old male patient with high-risk pulmonary embolism following multiple injuries from a fall and subsequent deep vein thrombosis. In August 2024, the patient was admitted to The Fourth Affiliated Hospital of Guangxi Medical University with the chief complaint of "5 days of general multiple traumas after a fall and 8 hours of dyspnea". Five days prior to admission, the patient was hospitalized at The First People's Hospital of Hechi City for multiple injuries caused by a fall, during which an inferior vena cava filter was placed due to lower extremity deep vein thrombosis. The day after filter implantation, the patient developed dyspnea. Despite mechanical ventilation and vasoactive drug support, the patient still presented with persistent refractory hypoxemia [pulse oxygen saturation (SpO2) 80%-85%] and hemodynamic instability (shock index>1). Emergency contrast-enhanced chest CT revealed embolism in the right main pulmonary artery. Upon consultation from the external hospital, the Pulmonary Embolism Response Team (PERT) of The Fourth Affiliated Hospital of Guangxi Medical University immediately initiated cross-regional rescue. Upon arrival at the external hospital, the modified venous-arterial extracorporeal membrane oxygenation (V-A ECMO) circuit was emergently established using a Crescent dual-lumen catheter to stabilize circulation. The patient was then safely transferred back to The Fourth Affiliated Hospital of Guangxi Medical University under ECMO support, and underwent emergency interventional pulmonary thrombectomy using the AngioJet system. Postoperatively, hemodynamic and blood oxygen parameters improved significantly. ECMO was successfully removed on the first postoperative day, with a total ECMO run time of approximately 28 hours. After ECMO weaning, the arterial oxygen saturation (SaO2) reached 97.8% with face mask oxygen, and the shock index decreased to 0.83. The patient was able to ambulate on the 5th postoperative day without chest tightness or dyspnea. Telephone follow-ups at 3, 6, and 12 months showed favorable recovery. The successful rescue of this patient validates the effectiveness and feasibility of the integrated model of "cross-regional PERT collaboration-modified V-A ECMO support-interventional surgery" for high-risk pulmonary embolism patients with transfer risks. This model enables the rapid and safe establishment of advanced life support, creating conditions for subsequent interventional surgery, and is an effective strategy for managing such complex high-risk pulmonary embolism cases. However, the optimization of the overall workflow and its generalizability still require further practice and verification through larger-sample clinical studies.
Background/Objectives: Chronic obstructive pulmonary disease (COPD) often coexists with heart failure (HF) and can complicate the interpretation of symptoms, biomarker profiles, and clinical deterioration. Its prognostic significance at the time of sodium-glucose cotransporter 2 inhibitor (SGLT2i) initiation remains incompletely defined. We therefore evaluated whether baseline COPD was associated with a greater biomarker burden and worse 12-month outcomes in a real-world HF cohort at the time of SGLT2i initiation. Methods: This prospective single-centre observational cohort included patients with HF enrolled in a tertiary registry between May 2022 and November 2024 in whom SGLT2i therapy was initiated. HF was diagnosed according to contemporary European Society of Cardiology (ESC) criteria on the basis of compatible symptoms and/or signs, objective structural or functional cardiac abnormalities on echocardiography, and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP). COPD status was defined by a documented pre-existing diagnosis at baseline. The primary endpoint was the 12-month time-to-first composite of all-cause death or unplanned hospitalization for acute decompensated HF. Results: Among 996 patients, 122 (12.2%) had COPD. Compared with patients without COPD, those with COPD more often had a smoking history, a higher comorbidity burden, a worse New York Heart Association (NYHA) class, higher baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) levels, and a lower estimated glomerular filtration rate (eGFR), whereas baseline HF pharmacotherapy was broadly similar. NT-proBNP remained higher at 6 and 12 months, whereas CRP remained higher at 6 months but not at 12 months. In multivariable Cox analysis adjusting for age, sex, major comorbidities, left ventricular ejection fraction (LVEF), renal function, high-density lipoprotein cholesterol (HDL-C), glycated haemoglobin (HbA1c), CRP, and log NT-proBNP, COPD remained independently associated with the primary endpoint (hazard ratio [HR] 2.610, 95% confidence interval [CI] 1.707-3.991; p < 0.001) and all-cause death (HR 2.097, 95% CI 1.246-3.532; p = 0.005). Conclusions: Among patients with HF starting SGLT2i therapy, baseline COPD identified a higher-risk cardiopulmonary phenotype characterized by a greater comorbidity burden, higher inflammatory and natriuretic biomarker levels, and worse 1-year outcomes. These observational findings support closer integrated cardiology-pulmonology follow-up.
Volume assessment in cardiac amyloid light chain (AL) amyloidosis is challenging during high-dose chemotherapy and autologous stem cell transplantation (SCT), as clinical findings and body weight may not accurately reflect intravascular congestion. A 45-year-old man with multiple myeloma, nephrotic syndrome, and cardiac AL amyloidosis developed marked volume fluctuations during induction therapy. Before SCT, an implantable pulmonary artery pressure (PAP) sensor was placed to guide diuretics, targeting a diastolic PAP of 22 mm Hg. During the peritransplant period, remote PAP monitoring enabled individualized diuretic titration despite mucositis, gastrointestinal losses, transfusions, neutropenic fever, delirium, and weight variation. He completed SCT without heart failure decompensation and achieved complete hematologic remission. This case highlights the value of PAP-guided management in complex cardio-oncology patients with dynamic hemodynamics. In cardiac AL amyloidosis, invasive hemodynamic monitoring may outperform clinical assessment. PAP-guided management may be useful during SCT when risks of congestion and hypovolemia coexist.
The global incidence of Mycobacterium avium complex pulmonary disease (MAC-PD) has been increasing, particularly in Japan. Although current guidelines recommend adding intravenous amikacin (AMK-IV) for cavitary or severe disease, evidence supporting its use as initial therapy remains limited, especially among elderly patients. This retrospective study included patients with cavitary MAC-PD who received an AMK-IV-containing regimen as initial therapy at Kurashiki Central Hospital between September 2021 and July 2024. AMK-IV dosing was adjusted based on therapeutic drug monitoring (TDM). The primary outcome was sputum culture conversion. Secondary outcomes included radiologic improvement, adverse events, recurrence, and all-cause mortality. Clinical characteristics and outcomes were compared between patients aged ≥75 and < 75 years. Twenty-one patients were analyzed (aged ≥75 years, n = 11; aged <75 years, n = 10; median age, 75 years; 76.2% female). TDM-guided dose adjustment of AMK-IV was performed in all patients, and outpatient treatment was continued using the adjusted dose. Target peak concentrations were achieved in 57.1% of patients, while target trough concentrations were achieved in all patients. At 6/12 months, sputum culture conversion was achieved in 56.3%/62.5% and radiologic improvement was observed in 83.3%/88.9%. No significant differences in sputum culture conversion or radiologic improvement were found between age groups. Treatment discontinuation occurred in two patients (9.5%), whereas 90.9% of elderly patients completed ≥3 months of AMK-IV. AMK-IV added to a standard regimen for cavitary MAC-PD may be effective and safe. In this TDM-guided protocol, favorable outcomes were observed despite lower peak concentrations than those generally recommended.
Systemic sclerosis-associated interstitial lung disease (SSc-ILD) remains an important cause of morbidity and mortality in systemic sclerosis. Mycophenolate mofetil (MMF) is widely used as first-line immunosuppressive therapy; however, real-world descriptions of pulmonary functional and radiologic evolution during MMF therapy remain limited, particularly according to high-resolution computed tomography (HRCT) pattern. Objectives: To descriptively evaluate pulmonary function evolution, radiologic findings, and safety outcomes in patients with SSc-ILD treated with MMF in routine clinical practice, with exploratory analyses according to HRCT pattern and subsequent antifibrotic use. Materials and Methods: We conducted a retrospective single-center study including 20 patients with SSc-ILD treated with MMF. Clinical, functional (forced vital capacity [FVC]; diffusing capacity for carbon monoxide [DLCO]), and radiologic (HRCT Warrick score) parameters were assessed at baseline, 6 months, and 12 months. Patients were stratified according to nonspecific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP) patterns. Statistical analyses were exploratory and descriptive. Results: Pulmonary function remained overall stable during follow-up under MMF therapy, while DLCO improvement was observed at 6 months and remained stable at 12 months. Radiologic progression appeared more limited in patients with NSIP pattern, whereas patients with UIP pattern generally exhibited more frequent radiologic progression during follow-up. Patients who subsequently received nintedanib generally presented with UIP-pattern disease, lower baseline DLCO values, and more advanced pulmonary involvement. MMF was generally well tolerated, with treatment discontinuation due to adverse events observed in a single patient. Conclusions: This small retrospective real-world case series describes pulmonary functional and radiologic evolution in patients with SSc-ILD treated with MMF in routine clinical practice. Overall functional stabilization was observed during follow-up, while radiologic progression was more frequently observed in patients with UIP-pattern disease and more advanced baseline pulmonary involvement. Because of the exploratory descriptive design and limited sample size, these observations should be interpreted cautiously and considered hypothesis-generating only. Further prospective studies with standardized radiologic assessment are required.
Here, we present the case of a 25-year-old patient with G542X and G85E cystic fibrosis mutations who underwent computed tomography examination before and after triple-combination therapy. Clear improvement in sinonasal and lung involvement is visible two years after modulator treatment initiation. To the best of our knowledge, this is the first report about sinonasal improvement demonstrated by computed tomography images in a patient with G542X/G85E mutations.
Osteoarticular tuberculosis (OATB) is one of the most common clinical types of extrapulmonary tuberculosis (EPTB), characterized primarily by progressive bone destruction and high morbidity. Standard anti-tuberculous chemotherapy has limited efficacy in reversing established bone damage. Vitamin D, a fat-soluble steroid hormone with immunomodulatory and bone-metabolic properties, shows promise as an adjunctive therapeutic agent. Mechanistically, vitamin D enhances anti-tuberculous immunity through multiple pathways: inducing antimicrobial peptide LL-37 expression, activating autophagic flux, and modulating Th1/Th17/regulatory T cell balance. At the bone level, vitamin D counteracts Mtb-induced destruction via the OPG/RANKL axis, Wnt/β-catenin signaling activation, and correction of secondary hyperparathyroidism. However, rifampicin-a cornerstone chemotherapy agent-accelerates vitamin D catabolism by inducing CYP3A4/CYP24A1, creating a clinically significant drug-nutrient interaction that exacerbates vitamin D depletion. Evidence supporting vitamin D supplementation remains predominantly derived from pulmonary tuberculosis (PTB) patients in randomized controlled trials (RCTs), with only one small-sample study specific to OATB (n = 41, 8 weeks). These PTB-derived trials employed single high-dose bolus regimens with 3-6 months follow-up, demonstrating modest benefits (HR 0.58-0.89) primarily in vitamin D-deficient subgroups, with negligible effects in replete populations. Direct applicability to OATB remains unverified. This review systematizes vitamin D's immunological and bone-metabolic mechanisms in OATB, critically appraises existing evidence quality and extrapolation limitations, and proposes an RCT framework with bone structural repair and functional recovery as primary endpoints. Our aim is to guide theoretical development and future clinical investigation of vitamin D as adjunctive therapy for OATB.
Background/Objectives: Pleura-based pulmonary nodules in soft-tissue sarcoma (STS) patients remain diagnostically challenging, and entity-specific contrast-enhanced ultrasound (CEUS) data are scarce. We aimed to characterize CEUS perfusion patterns of pleura-based STS pulmonary metastases in a pilot cohort. Methods: We investigated a single-center retrospective cohort at a tertiary STS referral center (Dec 2024-Dec 2025). Of 51 consecutive STS patients with suspected pulmonary metastases screened, 32 lacked pleural contact and 6 were excluded for logistical reasons; the remaining 13 underwent standardized CEUS of a pleura-contacting lesion (≥5 mm) visible on B-mode lung ultrasound (B-LUS), with 1 excluded on biopsy (anaplastic lymphoma). The reference standard combined histology, therapy-related size reduction of the index lesion, and/or documented distant metastatic STS. Two readers rated all examinations independently, with adjudication by a third senior reader. Wilson 95% confidence intervals (CIs) and Cohen's κ were computed. Results: In the 12 analyzed patients (mean age 58.8 ± 17.8 years; 7 male), the index lesion was histologically confirmed in 4 (33.3%). On CEUS, bronchial-arterial (BA) enhancement predominated (10/12; 83.3%, 95% CI 55.2-95.3%) and pulmonary-arterial timing occurred in 2/12 (16.7%). Marked enhancement was present in 9/12 (75.0%), homogeneous in 8/12 (66.7%), and rapid washout (<120 s) in all lesions (12/12; 100%, 95% CI 75.8-100%). Inter-reader agreement was substantial to almost perfect for the diagnostically relevant CEUS perfusion variables (enhancement κ = 0.75; EE κ = 0.80; HE κ = 0.82) and moderate for the descriptive shape variable (Form κ = 0.47). Conclusions: In this selected pilot cohort, pleura-based STS lung metastases most commonly showed BA-dominant enhancement with universal rapid washout. The findings are hypothesis-generating and require validation in larger, prospective multicenter cohorts.
Tuberculosis (TB) remains a major global public health concern, particularly in high-burden countries such as India. Pulmonary TB (PTB) is the most common form of the disease and the principal source of transmission. Although sputum smear microscopy using Ziehl-Neelsen (ZN) staining is widely employed for diagnosis, it has limited sensitivity, especially in patients with sputum smear-negative disease. These patients often present with strong clinical symptoms and radiological findings suggestive of PTB but lack microbiological confirmation, leading to diagnostic delay, inappropriate empirical therapy, and continued transmission. In this context, fiberoptic bronchoscopy (FOB) with bronchoalveolar lavage (BAL) offers an important diagnostic alternative by enabling direct airway evaluation and targeted sample collection. The use of molecular diagnostics, such as the cartridge-based nucleic acid amplification test (CBNAAT) on BAL samples, has further enhanced diagnostic yield. This cross-sectional observational study was conducted over 18 months at the Department of Pulmonary Medicine at L.N. Medical College and J.K. Hospital, Bhopal. Adult patients (≥18 years) with clinical features suggestive of PTB, such as cough, fever, weight loss, night sweats, or hemoptysis, and radiological findings consistent with PTB, but with at least two sputum samples negative for acid-fast bacilli (AFB) on ZN staining, were included. Patients with prior anti-tubercular therapy within six months, sputum-positive TB, pregnancy, or contraindications to bronchoscopy were excluded. A total of 97 patients were included. All patients underwent detailed clinical evaluation, chest imaging, and FOB performed under standard aseptic precautions. BAL samples were collected from radiologically involved lung segments and subjected to AFB smear microscopy and CBNAAT. Statistical analysis was performed to assess associations between clinical features, radiological findings, and BAL-CBNAAT results. The mean age of the study population was 48.98 ± 16.37 years. Almost all patients (95/97; 97.9%) were symptomatic, with cough (88/97; 90.7%) and fever (83/97; 85.6%) being the most common presenting complaints, followed by weight loss (77/97; 79.4%) and night sweats (56/97; 57.7%). Hemoptysis was infrequent (5/97; 5.2%). All patients had radiological findings suggestive of PTB as per the inclusion criteria. BAL-AFB smear was negative in all cases, highlighting the limited sensitivity of smear microscopy in sputum-negative disease. In contrast, BAL-CBNAAT detected Mycobacterium TB in 89 of 97 patients, yielding a diagnostic positivity rate of 91.75%. A statistically significant association was observed between BAL-CBNAAT positivity and clinical symptoms such as cough, fever, weight loss, and night sweats (p < 0.05), while hemoptysis showed no significant correlation. The study concludes that FOB with BAL, when combined with CBNAAT, has a high diagnostic yield in sputum smear-negative patients with clinico-radiological suspicion of PTB. This approach effectively overcomes the limitations of sputum-based diagnostics, enables early microbiological confirmation, and facilitates timely initiation of appropriate therapy. FOB should be considered a crucial diagnostic tool in the evaluation of sputum smear-negative PTB.
On-target, off-tumor toxicity presents a significant challenge in chimeric antigen receptor (CAR) T therapy for solid tumors. Traditional approaches to managing adverse reactions, such as suppressing in vivo CAR-T cell activity, risk impairing their antitumor efficacy, often resulting in treatment failure. Intravenously infused CAR-T cells initially traffic to the lungs, where they are activated by tumor-associated antigens (TAAs) expressed on pulmonary tissues, leading to acute lung injury. To address this, this study developed a strategy involving leukocyte function-associated antigen 1 (LFA-1) neutralization at the time of infusion. This approach modulates CAR-T cell pharmacokinetics to enhance efficacy while minimizing toxicity. Post-infusion, CAR-T cells preferentially sequester and activate in the lung, secreting tumor necrosis factor α (TNF-α), which upregulates intercellular adhesion molecule 1 (ICAM-1) expression on pulmonary endothelial cells. This triggers an "activation-adhesion" feedback loop via the LFA-1/ICAM-1 pathway, exacerbating lung injury. Neutralization of LFA-1 during infusion significantly reduces CAR-T cell adhesion to pulmonary endothelium, disrupts this feedback loop, and mitigates acute lung injury. By accelerating the pharmacokinetic progression of CAR-T cells beyond the lung, this strategy not only alleviates the acute toxicity associated with high-dose regimens but also enhances the antitumor efficacy of low-dose CAR-T cells, thus expanding the therapeutic window.
Pneumonia remains a major global health concern, particularly among elderly and immunocompromised populations, and is associated with substantial morbidity, mortality, and healthcare burden. It is a heterogeneous infectious disease caused by a wide variety of microorganisms, resulting in diverse imaging manifestations and characteristic patterns of pulmonary distribution. Despite advances in microbiological diagnostics and imaging, the literature still lacks a comprehensive overview integrating the imaging characteristics of pneumonia with pathogen-specific features and host susceptibility. A structured literature search of PubMed, Scopus, and Web of Science was conducted for studies published between 2000 and 2026 focusing on key pathogen groups and their radiological patterns. The reviewed evidence indicates that pulmonary distribution is determined by a complex interplay between infection routes, lung anatomy and physiology, host defense mechanisms, patient-specific, and environmental exposures. Radiological patterns, including lobar, bronchopneumonic, interstitial, necrotizing, abscess-forming, and cavitating forms, may correlate with pathogen type, disease severity, and host vulnerability. This integrative approach emphasizes the importance of correlating imaging findings with clinical presentation and patient risk factors to support early etiological assessment and guide empirical therapy. Improved understanding of the determinants of pulmonary distribution may facilitate personalized management, rapid clinical decision-making in emergencies and hospital settings, and improved clinical outcomes.
Pulmonary hydatid disease is uncommon in children and may present diagnostic difficulties, particularly when serology is negative. We report a 10-year-old boy from an endemic rural area who was incidentally found to have three giant pulmonary cysts involving both lungs. Despite negative Echinococcus serology, radiologic features were highly suggestive of hydatid disease. The patient underwent staged bilateral thoracoscopic endocystectomy with capitonnage following albendazole therapy. Histopathology confirmed the diagnosis. Postoperative recovery was uneventful, with complete radiological resolution and no recurrence at three-year follow-up. This case highlights the limitations of serology in isolated pulmonary hydatid disease and supports thoracoscopic lung-preserving surgery as an effective treatment in children.
Interstitial lung diseases (ILDs) are frequently characterized by the presence of pulmonary fibrosis (PF), which may lead to respiratory failure secondary to irreversible parenchymal distortion. Although idiopathic pulmonary fibrosis (IPF) is the clinical prototype, the emergence of the progressive pulmonary fibrosis (PPF) phenotype has shifted the therapeutic paradigm toward shared pathogenic pathways while preserving the need to recognize the biological and clinical heterogeneity of the underlying ILDs. This state-of-the-art review integrates recent experimental and clinical data to provide a comprehensive overview of the transition from inflammatory models to the current epithelial-centric framework of fibrogenesis. In particular, the shift from ineffective anti-inflammatory strategies to the success of nintedanib and pirfenidone in both IPF and non-IPF progressive diseases is discussed. Furthermore, recent advances from phase II and III clinical trials targeting specific molecular drivers of fibrosis and vascular remodeling are analyzed, with a focus on pathway-oriented therapies, including nerandomilast, admilparant, and inhaled treprostinil. Understanding this molecular crosstalk is essential for the development of new therapeutic strategy based on precision medicine and it may support a new era of combination approaches aimed at stabilizing disease and improving patient outcomes in both idiopathic and progressive pulmonary fibrosis.
 Sirolimus is the standard disease-modifying therapy for lymphangioleiomyomatosis (LAM), but long-term routine-care data integrating pulmonary, lymphatic, extrapulmonary, and biomarker outcomes remain limited.  To assess long-term effectiveness and safety of sirolimus in routine clinical practice. We retrospectively analyzed consecutive adults with definite LAM treated with sirolimus at a national tertiary referral center in Poland between 2010 and 2020. Seventy-one patients were included (70 women; 57/71 [80%] with sporadic LAM and 14/71 [20%] with TSC-associated disease). The median duration of available functional follow-up was 5.0 years [IQR, 2.0-5.0], and mean trough sirolimus concentration was 7.85 (2.36) ng/mL. Baseline chylous pleural and/or peritoneal effusions were present in 15/71 (21%), renal angiomyolipomas in 33/71 (46%), and lymphangioleiomyomas in 28/71 (39%) patients. FEV1 increased at 12 months by a median Δ of 0.03 L [IQR, -0.10 to 0.30] from baseline (n=66; P=0.03). FVC and 6-minute walk distance also improved during early follow-up, while TLCO remained generally stable. Chylous effusions resolved in all affected patients by 12 months without recurrence, and renal angiomyolipoma and lymphangioleiomyoma volumes decreased significantly in patients with paired MRI measurements. Higher baseline VEGF-D was associated with lymphatic involvement, and VEGF-D decreased during treatment. Adverse events were mostly mild; permanent discontinuation occurred in approximately 6%.  In routine practice, sirolimus was associated with long-term stabilization of lung function, marked improvement of lymphatic disease, reduction of angiomyolipoma burden, and acceptable tolerability. VEGF-D aligned with lymphatic phenotype and declined with treatment, supporting its role as a monitoring biomarker.
A high-fat diet (HFD) not only induces metabolic disorders but also causes oxidative damage to the lung tissue, triggering inflammatory responses. However, the detailed mechanisms by which HFD induces pulmonary oxidative stress and inflammation, particularly involving NF-κB/PPAR-γ signaling and lung microbiota, remain poorly understood, and effective dietary intervention strategies are still lacking. This study investigated the effects of HFD on lung tissue injury in mice and systematically evaluated the protective effects and potential mechanisms of Torreya grandis seed oil (TGO) and Torreya grandis seed diester oil (TGO-DG). After 12 weeks of HFD feeding, HFD group mice exhibited a marked increase in body weight (90.36%) compared with the control group, whereas body weight gain was significantly attenuated in the TGO (57.95%) and TGO-DG (55.78%) groups. Biochemical analyses revealed that the levels of malondialdehyde (MDA), nitric oxide (NO), and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) were significantly elevated in the HFD group, indicating pronounced oxidative stress and inflammatory responses in lung tissue. These symptoms were significantly attenuated by TGO and TGO-DG, with TGO-DG showing a more marked effect. Western blot (WB) results showed that both TGO and TGO-DG suppressed IL-6 expression and altered the expression of proteins in the NF-κB and PPAR-γ signaling pathways, which may contribute to the alleviation of pulmonary inflammation. Lung microbiota analysis revealed that TGO was associated with an increased proportion of Lactobacillus species, which correlated with the restoration of pulmonary microbial homeostasis. Overall, these results suggest that TGO and TGO-DG effectively alleviate HFD-induced oxidative stress and inflammation in lung tissue through regulation of inflammatory signaling pathways and lung microbiota composition. Notably, TGO-DG exhibited superior protective effects, highlighting its potential as a lipid ingredient.
Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by persistent airflow limitation and chronic airway inflammation. Current therapeutic strategies primarily offer symptomatic relief and are often limited by systemic side effects, inadequate lung deposition, and poor patient compliance. Naringin (NAR), a natural flavonoid with strong antioxidant, anti-inflammatory, and anti-fibrotic activities, has demonstrated potential in mitigating COPD-associated pathophysiology. However, its therapeutic application is restricted by poor water solubility, low bioavailability, and rapid metabolism. Nanotechnology-based drug delivery systems, particularly poly(lactic-co-glycolic acid) (PLGA) nanoparticles, provide an effective approach for lung-targeted therapy. Their nanoscale size promotes deep lung deposition, enhanced cellular uptake, reduced lung clearance, improved therapeutic efficacy, and reduced systemic side effects. The present study aimed to develop NAR-loaded PLGA nanoparticles (NAR PLGA NP) for enhanced cell-targeting in inflammatory lung conditions. NAR PLGA NP were prepared using the emulsion solvent evaporation method, with PLGA in the organic phase and soya lecithin (SL) with poly(vinyl alcohol) (PVA) as surfactants in the aqueous phase. A face-centered central composite design was employed to optimize the formulation. The optimized nanoparticles were characterized for size distribution by dynamic light scattering, entrapment efficiency, Transmission Electron Microscopy (TEM), Fourier Transform Infrared (FTIR), Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD), and in vitro drug release. The safety of PLGA and lecithin-coated PLGA nanoparticles (LC PLGA NP) was assessed using an MTT assay on lung epithelial cells, followed by cellular uptake studies, angiogenesis by chick Yolk Sac Membrane (YSM) assay, and in vitro evaluation of reactive oxidative stress (ROS) and anti-inflammatory activity. The optimized PLGA formulation showed a hydrodynamic diameter of 201 ± 1 nm with PDI 0.20 ± 0.03 and EE of 76.11 ± 2.1%, and 81.7 ± 4.9% drug release at 72 h, whereas LC PLGA NP showed a hydrodynamic diameter of 308 ± 3 nm, PDI of 0.21 ± 0.05, entrapment efficiency of 82.45 ± 4.8%, and 71.4 ± 3.2% drug release at 72 h. Both PLGA NP and LC PLGA NP demonstrated good cytocompatibility with lung epithelial cells, efficient cellular uptake, and a significant reduction in intracellular reactive oxygen species (ROS) levels (**** p value < 0.0001). Moreover, the formulations markedly suppressed pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, indicating anti-inflammatory activity. The angiogenesis assay further suggested their ability for lung tissue repair and remodeling. These findings support the potential of LC PLGA NP as a promising cell-specific targeting system for naringin in inflammatory lung conditions.
Sepsis remains a leading cause of mortality in intensive care units (ICUs) worldwide, affecting millions of patients annually. Although mechanical ventilation (MV) is a life-saving intervention in sepsis management, its association with patient outcomes remains controversial, with conflicting evidence regarding its impact on mortality. Current literature lacks a comprehensive analysis of the clinical phenotypes and laboratory parameters that may modify this relationship. This study aimed to evaluate the association between MV and 28-day mortality in ICU sepsis patients and to explore potential effect modifiers. We conducted a retrospective cohort study of adult sepsis patients admitted to the ICU of Fuqing Affiliated Hospital, Fujian Medical University, between January 1, 2017, and December 31, 2024. Sepsis was defined according to Sepsis-3 criteria. The primary exposure was invasive mechanical ventilation, and the primary outcome was 28-day all-cause mortality. Covariates included 25 variables encompassing demographics, seven comorbidities, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, vital signs, eleven laboratory parameters, and antibacterial therapy. We performed multi-variable logistic regression adjusting for these covariates to assess the MV-mortality association, with stratified analyses and interaction terms to evaluate effect modification. Among 673 ICU sepsis patients, 507 (75.3%) received mechanical ventilation. The 28-day mortality rate was significantly higher in the MV group than in the non-ventilation group (56.0% vs. 29.5%, p < 0.001). Multi-variable analysis demonstrated that MV was independently associated with increased 28-day mortality (adjusted odds ratio [OR] 2.62, 95% CI 1.67-4.11, p < 0.001). Stratified analyses revealed that chronic obstructive pulmonary disease (COPD) (p for interaction = 0.043), anion gap (p for interaction = 0.017), and serum creatinine (p for interaction = 0.020) significantly modified the MV-mortality association. The adverse association was substantially more pronounced in patients with an elevated anion gap (OR 6.62, 95% CI 3.28-13.38), lower serum creatinine (OR 3.73, 95% CI 1.85-7.54), and those without COPD (OR 3.23, 95% CI 2.19-4.78). Mechanical ventilation is independently associated with 28-day mortality in ICU sepsis patients, particularly in those with an elevated anion gap, lower serum creatinine, and without COPD. These findings highlight the importance of judicious MV use in sepsis patients and support individualized patient assessment and tailored respiratory management strategies in clinical practice. Identifier ChiCTR2500109053 https://www.chictr.org.cn/showproj.html?proj=283223.
Lung transplantation (LTx) is the definitive therapy for patients with end-stage lung disease and improves survival. However, many recipients continue to experience exercise intolerance, reduced physical capacity, and limitations in daily activities despite improved postoperative lung function. These impairments are multifactorial and closely associated with quality of life (QoL) and long-term outcomes. Pulmonary rehabilitation (PR) is a multidisciplinary intervention aimed at improving exercise capacity, physical fitness, and QoL and has demonstrated benefits across various chronic lung diseases. This narrative review synthesizes current evidence on PR in LTx recipients. A literature review was conducted to summarize PR program characteristics, safety, and reported outcomes across lung function, functional capacity, muscle fitness, activity and participation, and QoL, considering heterogeneity in study design and intervention protocols. Across the reviewed studies, PR participation was consistently associated with improvements in cardiorespiratory fitness, muscle strength, functional capacity, and QoL. In contrast, changes in spirometric parameters were generally modest. Functional improvements appear to be largely mediated by peripheral adaptations, including enhanced oxygen utilization and neuromuscular performance. These findings highlight the potential role of PR as an important component of short- and long-term management in LTx recipients, particularly during pre-transplant conditioning and post-transplant functional recovery phases.