Search Results (1,264)

Pulmonary hypertension associated with interstitial lung disease (PH-ILD) is associated with substantial morbidity and mortality. Lung transplantation remains the definitive therapy for selected patients; however, severe pulmonary vascular dysfunction and hemodynamic instability may complicate transplant candidacy and pre-transplant management. The role of parenteral prostacyclin therapy as a bridge to transplantation in this population remains poorly defined. The primary objective of this retrospective case series was to evaluate the utility of parenteral treprostinil as a bridge therapy for lung transplantation in 14 patients with severe PH-ILD from 2018 to 2025. Secondary objectives were to describe subsequent changes in clinical outcomes, including hemodynamic parameters measured by right heart catheterization, echocardiographic findings, the six-minute walk distance, oxygen requirements, the need for veno-arterial extracorporeal membrane oxygenation (VA-ECMO), and successful lung transplantation. Parenteral treprostinil was associated with significant improvements in pulmonary artery systolic pressure, mean pulmonary artery pressure, pulmonary vascular resistance, and BNP levels, while pulmonary capillary wedge pressure, cardiac output, cardiac index, and oxygen requirements remained stable following therapy initiation. Echocardiography demonstrated improvement in right ventricular dilation and right ventricular dysfunction. Most patients were successfully bridged to lung transplantation, while only two patients died prior to transplantation. In selected patients with severe PH-ILD, parenteral treprostinil may improve pulmonary hemodynamics and facilitate a successful bridge to lung transplantation without worsening oxygenation. Full article

Background and Clinical Significance: Interstitial lung disease (ILD) is an uncommon but potentially serious complication of imatinib. Its histopathological characterization has so far relied on surgical biopsy or transbronchial forceps sampling, and no case characterized by transbronchial lung cryobiopsy (TBLC) has been reported. The single previous description of a non-specific interstitial pneumonia (NSIP) pattern with imatinib came from a surgical specimen and was cellular in type, with complete radiological resolution after withdrawal. Case Presentation: A 69-year-old never-smoker began imatinib 400 mg daily for Philadelphia chromosome-positive chronic myeloid leukemia; chest computed tomography performed immediately beforehand was normal. Approximately three months later, she developed dyspnea, dry cough and a cutaneous rash, progressing to acute respiratory failure with forced vital capacity 49% and diffusing capacity 30% of predicted. Avian exposure had ceased one month before symptom onset, and she had never received amiodarone. Although serum precipitins were unavailable, hypersensitivity pneumonitis was considered less likely given the temporal relationship but could not be definitively excluded. TBLC yielded specimens showing fibrotic thickening of the alveolar septa by hyaline collagen deposition with a focal lymphomonocytic infiltrate, corresponding to a fibrotic NSIP pattern. After drug withdrawal and administration of corticosteroids, forced vital capacity rose to 82% of predicted. Multidisciplinary discussion concluded that this was drug-induced ILD, graded probable on the Naranjo scale. Imatinib was subsequently replaced by bosutinib for insufficient molecular response, without pulmonary recurrence. Conclusions: Imatinib-associated ILD may present with an organizing-pneumonia-like radiological pattern followed by a fibrosing pattern, with cryobiopsy performed later demonstrating fibrotic NSIP. Because no tissue was obtained during the acute phase, this sequence remains a hypothesis rather than a demonstrated evolution. Cryobiopsy can be performed safely when surgical biopsy is not appropriate. Full article

Background/Objectives: To develop and evaluate an automated CT-based framework for the quantitative assessment of fibrotic interstitial lung disease (ILD), including idiopathic pulmonary fibrosis (IPF), using a standardised six-level anatomical protocol and deep-learning lung segmentation. Methods: The segmentation dataset comprised 3315 manually annotated development slices from 92 patients and a non-overlapping internal holdout of 845 slices from 5 patients. A separate 100-study localisation/scoring set yielded a 97-patient agreement cohort (84 IPF, 13 other ILD; 1164 per-level, per-lung observations) after three DICOM-conversion exclusions. YOLO11n-seg masks underwent vessel- and structure-removal fibrosis detection. The radial spatial score was compared with a non-blind expert-adjudicated reference; the per-level Fibrosis Index was an auxiliary read-out. Results: On the five-patient internal segmentation holdout, mean intersection over union (mIoU) was 0.926 ± 0.017; the in-sample development value was approximately 0.95. Model-only latency was 73.8 ± 9.7 ms/slice at batch size 1, and peak throughput was 1.48 ms/slice at batch size 512. In the separate 97-patient agreement cohort, the expert-adjudicated score was identical to the automated score for 967 of 1164 observations (83.1%) and differed for 197 (16.9%). In the modified-score subset, Pearson r was 0.918, mean absolute error was 3.07, and ICC(2,1) was 0.889 (patient-clustered 95% CI 0.828–0.923). The pooled ICC(2,1) was 0.988 (0.982–0.992), but this value was inflated because the 967 unchanged pairs were identical by construction. Sequential end-to-end processing, measured in seven study patients, took a mean of 22.5 s per patient (median 24.0 s, range 17.3–24.9 s); localisation accounted for 88.1% of this time. Conclusions: The framework combined lung segmentation, anatomically standardised sampling, and automated fibrosis scoring. The radial score showed preliminary analytical concordance under non-blind expert adjudication. The fibrosis detector remains a proof-of-concept implementation based on 8-bit windowed images and has not been compared with independently drawn pixel-level fibrosis masks. The radial partition is an exploratory scoring convention and was not compared with alternative partitions or validated against clinical outcomes. Larger external studies using native Hounsfield-unit data and independent blinded readers are required. Full article

Systemic sclerosis (SSc) is a heterogeneous autoimmune disease characterized by immune dysregulation, vasculopathy, and progressive fibrosis affecting the skin and internal organs. Although biologic therapies have expanded the therapeutic landscape of immune-mediated diseases, their impact in SSc has been uneven and remains difficult to interpret when viewed only on a drug-by-drug basis. This focused narrative review reappraises biologic therapies in SSc using a manifestation-based framework spanning cutaneous, pulmonary, vascular, gastrointestinal, musculoskeletal, and global or composite outcomes. Published evidence is most developed for selected cutaneous and pulmonary manifestations, particularly through B-cell depletion in selected cutaneous–pulmonary phenotypes and interleukin-6 blockade that attenuates pulmonary function decline in early inflammatory disease, whereas gastrointestinal and vascular manifestations have not yet shown comparable clinical evidence of benefit and remain insufficiently studied. We argue that this asymmetry not only reflects differences in trial design and endpoint selection, but also manifestation-specific pathobiology, disease stage, and the extent to which inflammatory, vascular, and fibrotic processes remain therapeutically modifiable. In particular, vasculopathy may represent an upstream pathogenic layer that constrains the disease-modifying capacity of biologics that primarily improve downstream inflammatory or fibrotic manifestations. We also highlight the relevance of Japanese contributions to the biologics literature in SSc and discuss future priorities, including manifestation-appropriate endpoint selection, early-disease enrichment, and biomarker-informed stratification. Overall, biologics have changed the treatment of SSc in a selective rather than global manner; embracing a manifestation-based view is now essential for both trial design and day-to-day therapeutic decision-making. Full article

Purpose: Trastuzumab deruxtecan (T-DXd) has significantly improved outcomes in patients with HER2-positive and HER2-low/ultralow metastatic breast cancer (MBC). However, most patients eventually discontinue treatment. In clinical trials, discontinuation without disease progression occurred in 30–60% of cases, but real-world data on the reasons for discontinuation and subsequent treatment strategies remain limited. This study aimed to describe T-DXd discontinuation patterns and post-discontinuation treatments in a real-world setting. Methods: We conducted a single-center retrospective observational study including consecutive patients with MBC treated with T-DXd between July 2018 and December 2025. Patients who discontinued T-DXd for any reason were included. Reasons for discontinuation, treatment duration, response outcomes, and subsequent systemic therapies were analyzed using descriptive statistics. Results: Overall, 93 patients were included: 71.0% had HER2-positive, 26.9% HER2-low, and 2.1% HER2 0 tumors. The primary reason for discontinuation was progressive disease (82.8%). Other reasons included adverse events (14.0%), non-treatment-related causes (2.2%) and patient decision (1.1%). Interstitial lung disease represented the most common toxicity leading to discontinuation (10.8%). The median treatment duration was 7.9 months overall and was longer in patients with HER2-positive than in thosewith HER2-low and HER2 0 disease. Among evaluable patients, overall response rate was 83.1% in HER2-positive tumors and 52% in HER2-low tumors. After discontinuation, 80.6% of patients received subsequent therapy. Patients discontinuing for reasons other than progression had longer treatment exposure. Conclusions: In this real-world cohort, most T-DXd discontinuations were due to disease progression, while adverse event-related discontinuations were less frequent than in clinical trials. Several factors may influence treatment persistence, including toxicity management. Further evaluation in larger, multicenter cohorts is warranted to better characterize their contribution. Full article

Systemic sclerosis (SSc) is a heterogeneous autoimmune connective tissue disease characterized by immune activation, vasculopathy and progressive fibrosis of the skin and internal organs. Immunosuppressive treatment is commonly used in early inflammatory disease and in SSc-associated interstitial lung disease (SSc-ILD), yet the optimal first-line agent depends on the dominant clinical phenotype. Methotrexate (MTX) and mycophenolate mofetil (MMF) are two widely used conventional immunomodulatory options. This review summarizes the clinical trial evidence from the last four decades and places it into the context of contemporary guideline recommendations and real-world comparative effectiveness data. Two randomized placebo-controlled trials support a modest role for MTX in early diffuse cutaneous SSc, particularly for skin and musculoskeletal manifestations, but evidence for lung benefit is limited. MMF has stronger evidence for SSc-ILD, principally from the Scleroderma Lung Study II, a randomized double-blind trial showing comparable efficacy to oral cyclophosphamide with better tolerability, and from subsequent pilot, open-label, and real-world studies. Overall, the current evidence supports a phenotype-driven approach: MTX may be considered when skin or joint disease predominates without clinically relevant ILD, whereas MMF is generally preferred for SSc-ILD and systemic inflammatory disease. Direct head-to-head MTX versus MMF trials are lacking and remain an important research priority. Full article

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by parenchymal scarring, increased tissue stiffness, and impaired gas exchange. This study investigates the fluid dynamics and structural response of central airways in both healthy and fibrosis-inspired lungs under a 50% increased flow demand. A three-dimensional airway geometry was reconstructed from computed tomography (CT) scans up to the fifth bronchial generation using a hybrid modeling approach. Transient computational fluid dynamics (CFD) simulations of inhalation and exhalation were performed using ANSYS Fluent with the SST k-ω turbulence model. A complementary static structural analysis was conducted to assess deformation and stress under pleural pressure loading. The results indicate that fibrosis-inspired lungs required 92% higher inlet pressure losses compared to healthy lungs, highlighting the increased energetic cost of breathing. Flow patterns remained qualitatively similar. Structurally, fibrosis-inspired tissue exhibited 17% lower equivalent elastic strain under the same pressure load, confirming the impact of increased stiffness on bronchial distensibility. Maximum principal stress concentrations of 22.1 kPa were identified at the left main bronchus bifurcation, indicating potential mechanical stress hotspots. Full article

Background and Objectives: Krebs von den Lungen-6 (KL-6) is a promising biomarker of interstitial lung disease (ILD), but data in immune-mediated ILD remain limited. We aimed to evaluate the clinical, functional, and radiological correlates of serum KL-6 levels in a real-world cohort of patients with immune-mediated ILD. Materials and Methods: We conducted a retrospective, cross-sectional, single-center study including adults with multidisciplinary follow-up for immune-mediated ILD and at least one serum KL-6 determination between January 2023 and September 2025. Clinical, laboratory, radiological, and pulmonary function data closest to the index KL-6 measurement were collected. KL-6 was analyzed as both a continuous variable and a categorical variable using a predefined cutoff of 500 U/mL. Correlation analyses and multivariable logistic regression were performed to identify factors independently associated with elevated KL-6 levels. Results: A total of 112 patients were included; 72.3% were women, with a median age of 70 years (IQR 63–77). The most frequent underlying diseases were systemic sclerosis (30.4%), rheumatoid arthritis (25.9%), and inflammatory myopathy (14.3%). Median KL-6 concentration was 770.5 U/mL (IQR 437.3–1148.5). Patients with FVC < 80% predicted and DLCO < 60% predicted had significantly higher KL-6 levels than those with better lung function (p = 0.001 and p = 0.004, respectively). KL-6 levels correlated inversely with DLCO (% predicted) (ρ = −0.388, p < 0.001) and FVC (% predicted) (ρ = −0.328, p < 0.001) but not with the presence of radiological fibrosis. In the multivariable analysis, lower DLCO (% predicted) (OR 0.919, 95% CI 0.884–0.955; p < 0.001) and older age (OR 1.063, 95% CI 1.014–1.115; p = 0.012) were independently associated with elevated KL-6 levels. Conclusions: Elevated serum KL-6 concentrations were associated with impaired gas transfer as measured by DLCO % predicted in this cross-sectional cohort. Longitudinal studies are required to determine whether KL-6 can predict functional decline, disease progression, or clinical outcomes. Full article

Group 3 pulmonary hypertension is a common and clinically significant complication of chronic lung disease and hypoxia that is associated with impaired functional capacity, right ventricular dysfunction, and increased mortality. Historically viewed as a consequence of underlying parenchymal lung disease, Group 3 pulmonary hypertension is now recognized as a complex disorder involving pulmonary vascular remodeling, dysregulated molecular signaling, and maladaptive cardiopulmonary interactions. Advances in translational research have improved our understanding of the mechanisms driving disease progression and have informed the development of targeted therapeutic strategies. This review provides an overview of the current understanding of Group 3 pulmonary hypertension, including its pathophysiology, diagnostic evaluation, and evolving treatment landscape. Specifically, this review dives into the reason behind limited therapeutic success, the outcomes of previous clinical trials, and the emergence of lung-selective approaches that seek to balance pulmonary vascular benefit with preservation of gas exchange. Collectively, these developments highlight both the progress made and the ongoing need for improved phenotyping and novel therapeutic approaches in the Group 3 pulmonary hypertension patient population. Full article

Interstitial lung disease (ILD) is a frequent manifestation and a leading cause of morbidity and mortality in idiopathic inflammatory myopathies (IIM), particularly in antisynthetase syndrome (ASyS) and anti-melanoma differentiation-associated protein 5 (MDA5) dermatomyositis. Although these disorders share common features of interstitial lung diseases, they differ substantially in pathogenesis, clinical phenotype, prognosis, and therapeutic response. There is also variability amongst the different subtypes of IIM-ILD. Recognition of these distinctions is essential for accurate diagnosis and treatment; delays in care, especially in cases of rapidly progressive ILD (RP-ILD), can be associated with high mortality. This review focuses on ILD in IIM, focusing on ASyS and anti-MDA5 dermatomyositis, highlighting similarities and key differences in disease mechanisms, clinical presentation, diagnostic evaluation, prognostic biomarkers, and management strategies. Full article

Background and Objectives: Interstitial lung disease (ILD) is an uncommon but clinically important manifestation of systemic lupus erythematosus (SLE). We aimed to identify factors associated with SLE–ILD, evaluate factors associated with clinical outcomes in established disease, and quantitatively synthesize comparable data. Materials and Methods: PubMed, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials were searched from inception through July 2026. English-language observational studies of adults with SLE reporting factors associated with ILD occurrence or outcomes in established SLE–ILD were eligible. Random-effects meta-analyses were conducted when at least three studies reported comparable data. Results: Eight observational studies were included. Across five studies, patients with SLE–ILD were older than those without ILD (mean difference 8.49 years, 95% confidence interval [CI] 5.52–11.46; p < 0.0001; I² = 66.9%). Across three studies, SLE–ILD was associated with higher odds of Raynaud phenomenon (odds ratio, 3.01; 95% CI, 1.49–6.09; p = 0.0022; I² = 28.8%). Other study-level associations included smoking, serositis, features of overlap connective tissue diseases, selected autoantibodies, and Krebs von den Lungen-6 (KL-6). In established SLE–ILD, baseline forced vital capacity and cohort-specific clinical and imaging features were associated with outcomes, while population-based cohorts linked ILD with increased mortality. Conclusions: Older age and Raynaud phenomenon were the factors most consistently associated with SLE–ILD across the available comparative studies. Because most included studies were observational, these findings should be interpreted as associations rather than evidence of causality. Prognostic evidence remains limited and heterogeneous. Full article

Background and Objectives: Antibody–drug conjugates (ADCs) have become a major therapeutic platform in breast cancer and other solid tumors. Trastuzumab deruxtecan (T-DXd), trastuzumab emtansine (T-DM1), and sacituzumab govitecan (SG) differ substantially in antibody target, linker, payload, drug-to-antibody ratio, and bystander effect, resulting in heterogeneous pulmonary and cardiac toxicity profiles. This narrative review critically compares interstitial lung disease (ILD)/pneumonitis and cardiotoxicity associated with these three agents, aiming to prevent inappropriate extrapolation of toxicity algorithms and to provide a practical, agent-specific framework for multidisciplinary care. Materials and Methods: A targeted narrative search of PubMed/MEDLINE, Google Scholar, ClinicalTrials.gov, regulatory product information, and oncology/cardio-oncology guidance was performed and updated on 24 August 2026. Priority was given to regulatory documents, pivotal trials, pooled safety analyses, real-world cohorts, systematic reviews, and multidisciplinary recommendations. Pharmacovigilance data and case reports were included only to characterize rare events. Results: T-DXd is associated with a clinically important ILD/pneumonitis risk (approximately 12–15% in pooled analyses), predominantly grade 1–2 but occasionally fatal, requiring proactive surveillance, immediate interruption for suspected disease, and grade-directed corticosteroid therapy. T-DM1 shows a low but established pneumonitis incidence of approximately 1%, with permanent discontinuation recommended upon diagnosis. SG-related pneumonitis is rare and incompletely defined, without a T-DXd-like surveillance mandate. Both T-DM1 and T-DXd retain trastuzumab-derived cardiac monitoring requirements; symptomatic heart failure remains uncommon, although protocol-defined LVEF declines appear more frequent with T-DXd. SG lacks an established cardiomyopathy signal. Conclusions: Cardiopulmonary toxicity of ADCs is agent-specific rather than a class effect. Monitoring intensity, diagnostic thresholds, and management pathways must be tailored to the individual drug, regimen, indication, dose, patient comorbidity, and prior therapy. Close collaboration among oncology, radiology, pulmonology, and cardio-oncology is essential to preserve both treatment efficacy and patient safety. Full article

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by excessive extracellular matrix remodeling and limited therapeutic options. Matrix metalloproteinase-2 is involved in extracellular matrix degradation and tissue remodeling, making it a relevant target for antifibrotic drug discovery. In this study, an MMP2-focused ligand-based pharmacophore model was developed and was applied to screen a curated FDA-approved drug library, leading to the identification of 83 pharmacophore-matching compounds. These compounds were subsequently prioritized through molecular docking against the catalytic site of MMP2, and the five best candidates were further evaluated by molecular dynamics (MD) simulations. Because of the biological relevance of MMP3 in pulmonary fibrosis, these five selected compounds were also profiled against MMP3 as a secondary target. Among them, Regorafenib (S1178) and Capmatinib (S2788) showed the most favorable cross-target profiles and were further supported by MD analysis. From these findings, S1178 and S2788 were proposed as promising MMP2-prioritized compounds with potential MMP3 cross-activity, warranting further experimental validation as candidate antifibrotic MMP modulators. Full article

Tracheal intubation in patients at risk of acute hypoxemic respiratory failure (AHRF) carries a high risk of life-threatening desaturation, and the choice of peri-intubation oxygenation strategy critically influences patient safety. This narrative review synthesizes current evidence on non-invasive oxygenation techniques—high-flow nasal oxygen (HFNO), non-invasive ventilation (NIV), and their combination—across the pre-oxygenation, apneic, and awake-intubation phases of airway management. We examine the physiological mechanisms underlying each modality, appraise landmark randomized trials and meta-analyses (including PREOXI, OPTINIV, and OPTIMASK), and address disease-specific considerations in chronic obstructive pulmonary disease, heart failure, interstitial lung disease, severe obesity, obstructive sleep apnea, and obstetric, pediatric, and trauma populations. The evidence supports a phenotype-driven hierarchy rather than a single dominant technique: NIV—optionally combined with HFNO for apneic oxygenation—is preferred in severely hypoxemic critically ill patients, whereas HFNO alone is adequate for many moderately hypoxemic or non-hypoxemic patients. Progressive hypercapnia limits apneic oxygenation, particularly in chronic CO₂ retainers, underscoring the value of continuous CO₂ monitoring. Persistent under-implementation of NIV-based pre-oxygenation reveals a gap between evidence and practice. Individualized, physiology-guided oxygenation—aligned with the goals of personalized peri-procedural medicine—offers the greatest potential to reduce peri-intubation morbidity. Full article

Background/Objectives: Intravascular large B-cell lymphoma (IVLBCL) is a rare and diagnostically challenging disease, often presenting as fever of unknown origin (FUO). This study aimed to develop and validate diagnostic predictive models and scoring systems to distinguish IVLBCL from other causes of FUO in hospitalized patients. Methods: A retrospective analysis was conducted in patients with IVLBCL or other causes of FUO who were treated between February 2015 and October 2023. Two multivariable logistic regression models and corresponding integer-based scoring systems were developed in a training cohort comprising 42 patients with IVLBCL and 45 FUO controls. Internal validation was performed using leave-one-out cross-validation and bootstrap resampling, followed by temporal validation in an independent cohort of 18 patients with IVLBCL and 21 FUO controls. Model 1 was additionally evaluated for sensitivity in an external case-only cohort comprising 40 patients with IVLBCL from eight hospitals. Results: Model 1 incorporated peripheral edema, hypoxemia, neurological symptoms, hemophagocytic lymphohistiocytosis, and interstitial lung abnormalities on computed tomography and achieved an area under the receiver operating characteristic curve (AUC) of 0.916 in the training cohort. Model 2 combined the interleukin-10/interleukin-6 (IL-10/IL-6) ratio with peripheral edema, hypoxemia, and neurological symptoms and demonstrated significantly improved discrimination (AUC = 0.982, p = 0.021 vs. Model 1). In the temporal validation cohort, the AUCs of Models 1 and 2 were 0.975 and 0.997, respectively. The corresponding integer-based scoring systems achieved AUCs of 0.903 and 0.952 in the training cohort and 0.926 and 0.992 in the temporal validation cohort. In the external case-only cohort, both Model 1 and its integer-based score identified 32 of 40 patients, yielding a sensitivity of 80.0%. Random skin biopsy provided the histological diagnosis in 58% of cases, with a positivity rate of 79.5%. Conclusions: Two diagnostic models and their simplified scoring systems were developed and internally and temporally validated to aid the diagnosis of IVLBCL in hospitalized patients with FUO. These models may assist in the diagnostic workup of hospitalized FUO patients, especially when IL-10/IL-6 testing is unavailable. Their performance in outpatient or community settings remains uncertain, and prospective multicenter validation with appropriate FUO controls is warranted. Full article