Citations

Abstract Interstitial lung disease (ILD) is a chronic, irreversible condition that is challenging to diagnose due to subtle symptoms and limitations of conventional tools. Noninvasive lung sound analysis using phonopulmography offers a promising alternative. This study evaluated the feasibility of a deep learning model for distinguishing normal and pathological lung sounds in ILD. Lung sound recordings were collected from 12 subjects (6 healthy, 6 ILD) and segmented beat-to-beat using simultaneously acquired ECG and phonopulmography, yielding 2,280 segments. Mel-frequency cepstral coefficients (MFCCs; 13 per segment) were extracted, and a one-dimensional CNN-based You Only Listen Once (YOLO) model was trained for segment classification. Evaluation used Leave-One-Out Cross-Validation, with patient-level classification by aggregating segment predictions via majority vote. On the test set (190 segments per class), the model achieved an average segment-level accuracy of 0.738 ± 0.087 and mean AUC of 0.850 ± 0.062. Precision, recall, and F1-score were 0.775 ± 0.148, 0.755 ± 0.183, and 0.738 ± 0.089, respectively. These preliminary results suggest that beat-level MFCCs with a 1D CNN-based YOLO model enable accurate segment- and patient-level classification. This feasibility study highlights the potential of AI-assisted auscultation for noninvasive monitoring and clinical decision support in ILD management, pending further validation in larger cohorts.

Microplastics may pose health risks, particularly for chronic lung diseases. Clarifying the link between circulating microplastics and pulmonary disease is vital for shaping research and interventions. The objective of this study was to evaluate whether microplastics in peripheral blood are associated with COPD or IPF vs. no lung disease. In this pilot prospective case-control study, participants were grouped as control (n = 10), COPD (n = 9), or IPF (n = 10). Relevant comorbidities and exposures were obtained from records and questionnaires. All underwent standardized blood collection (PlasticTox©). Samples were analyzed for total microplastic concentration, stratified by size (<10 µm, 10–30 µm, 30–70 µm). The primary outcome was to show a difference in total microplastic burden between lung disease and controls. Secondary measures were to determine size-specific concentrations and associations with demographic variables and smoking history. Among 29 participants (median age 70 (IQR 64–80); 14 women (48.3%)), COPD/IPF groups had significantly higher total microplastic concentrations vs. controls (median 26.0 vs. 3.5 particles/100 µL; p < 0.01). Particle burdens <10 µm and 10–30 µm were particularly elevated (both p < 0.01). After adjusting for smoking, only the <10 µm fraction remained independently associated with lung disease (adjusted odds ratio 1.94 (95% CI, 1.23–7.04)). In this pilot exploratory study, individuals with COPD or IPF showed greater circulating microplastic levels than controls. These findings should be interpreted as hypothesis-generating, and larger analytically validated studies are needed to clarify directionality, causal mechanisms, contamination control, and the clinical relevance of circulating microplastic burden.

Abstract Background: Primary Cardiac Lymphoma (PCL) is an exceptionally rare malignancy. While clinical case reports have postulated an association with human immunodeficiency virus (HIV), large-scale epidemiological data corroborating this link are limited. Objective: To determine whether HIV is associated with increased prevalence of PCL in a large, nationally representative sample of US hospitalizations. Methods: We performed a retrospective, cross-sectional analysis using the Healthcare Cost and Utilization Project National Inpatient Sample from 2016 to 2019, representing approximately 35 million unweighted hospitalizations. Hospitalizations were identified using a proxy definition for PCL, requiring ICD-10-CM codes for both cardiomyopathy (I42.*) and extranodal non-Hodgkin lymphoma (i.e., C83.39, C85.99). HIV status was identified using codes B20-B24 and Z21. We compared the prevalence of PCL in hospitalizations with versus without HIV and calculated odds ratios using Fisher’s Exact Test, reporting corresponding 95% confidence intervals (CI) and p-values. Results: We identified 569 hospitalizations meeting our operational definition for PCL out of 34,955,252 total discharges. The prevalence of PCL was significantly higher among hospitalizations with HIV (6.2 per 100,000) compared with those without HIV (1.6 per 100,000; p &lt; 0.0001). HIV was associated with a 3.86-fold increased odds of PCL (OR: 3.86; 95% CI: 2.23-6.70; p &lt; 0.0001). Conclusion: In this nationwide analysis of 35 million hospitalizations, HIV was strongly associated with a higher prevalence of PCL. Hospitalizations with HIV had nearly 4-fold higher odds of PCL, as defined by co-occurrence of cardiomyopathy and extranodal lymphoma, compared with hospitalizations without HIV. This population-level finding evinces the association previously suggested in clinical case reports. Citation Format: Omar Hozayen, Jay Hozayen, Benjamin Behers, Christoph Stephenson-Moe, Maha Hameed, Matthew Miller, Laura De Jesus Herrera, Anas Abu Jad, Rheiner Kammer, Mohab Idriss, Ahmed Aboutaleb, Bashar Roumia, Patricia Riano, Nicolas Riveros Neira, Brooke Hartenstein, Robert Taylor, Manuel Rosario Espinal, Brett M. Behers, Alya Hozayen, Mohamed Ibrahim, Karen Hamad. Primary cardiac lymphoma and HIV: A nationwide analysis of hospitalizations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 215.

Background: Direct oral anticoagulants (DOACs) are now the preferred anticoagulant over vitamin K antagonists for patients with atrial fibrillation (AF) and venous thromboembolism (VTE). Variability in drug exposure raises concerns about bleeding and thrombotic events, highlighting the potential value of therapeutic drug monitoring (TDM). Methods: This systematic review and meta-analysis conducted a systematic search of PubMed, Embase, Web of Science, Scopus, Cochrane Library, and ClinicalTrials.gov (from inception to May 2025) and identified studies reporting DOAC levels and clinical outcomes. Two reviewers independently performed screening, data extraction, and risk-of-bias assessment (RoB 2.0, Newcastle–Ottawa Scale). Random-effects meta-analytical models generated pooled estimates, with meta-regression exploring potential sources of variability (DOAC type, drug levels) and exposure–response relationships. Results: Nineteen studies comprising 5770 patients were included in the review. The pooled event rates were 8% for major bleeding (95% CI: 0.05–0.11), 7% for thrombotic events (95% CI: 0.05–0.09), and 3% for mortality (95% CI: 0.03–0.04). Heterogeneity was substantial for bleeding and thrombotic events (I2 = 95.6% and 87.3%, respectively) but negligible for mortality (I2 = 0%). Meta-regression analyses showed no significant association between mean DOAC concentration and either major bleeding (β = −0.00021, p = 0.35, Adj R2 ≈ 0%) or thrombotic events (β = 0.00005, p = 0.78, Adj R2 ≈ 0%), indicating that variations in measured plasma levels did not meaningfully explain event rate differences across studies. Conclusions: In this systematic review and meta-analysis, measured DOAC concentrations show limited and inconsistent association with clinical outcomes. While the present synthesis does not demonstrate a statistically robust linear correlation between DOAC plasma concentrations and adverse outcomes, it highlights the multifactorial determinants of bleeding and thrombosis risk underscores the potential value of selective TDM in individualized care. Further prospective, standardized studies are needed to define clinically actionable thresholds and to validate TDM-guided strategies that optimize the delicate balance between safety and efficacy in DOAC therapy.

Abstract Aims Obesity, particularly visceral adiposity, is a key driver of cardiovascular mortality (CVM), yet conventional measures such as body mass index (BMI) inadequately capture fat distribution. The Body Roundness Index (BRI) is a novel anthropometric measure integrating waist circumference and height to better reflect body shape and visceral fat. This study examined the association between BRI and CVM in U.S. adults and across sociodemographic subgroups. Methods and results We analysed data from 31 351 adults (median age 43 yrs, 50% females) aged ≥20 years in NHANES 1999–2018, excluding those with prior cardiovascular disease or cancer. BRI was computed using a validated equation and categorized into quintiles (Q3 as reference). The primary outcome was CVM; secondary outcomes included all-cause, heart disease, and cerebrovascular mortality. Weighted Cox proportional hazards and restricted cubic spline (RCS) models evaluated associations after adjustment for demographic, behavioural, and clinical factors. Subgroup and sensitivity analyses tested consistency and effect modification. During a median follow-up of 10.1 years (IQR: 5.3–14.9 years), 883 cardiovascular deaths occurred. In fully adjusted models, participants in the highest BRI quintile had a 54% higher risk of CVM (HR, 1.54; 95% CI, 1.13–2.08; P = 0.006) vs. Q3. This risk remained high even among those with normal BMI. RCS analysis indicated a modest U-shaped association. Stronger effects were observed among middle-aged adults (45–64 years) and those with higher educational attainment. Conclusion Higher BRI is independently associated with increased cardiovascular mortality, particularly among middle aged adults and those with normal BMI, underscoring its potential as a practical, noninvasive tool for cardiovascular risk stratification. Incorporating BRI into clinical and public health assessment may improve identification of individuals at elevated risk.

Abstract Background: Sickle cell disease (SCD) is marked by wide variability in clinical phenotypes and severity due to environmental, clinical, and genetic factors. Variants in iron-regulatory genes are well described modifiers of clinical presentation in different diseases, but their role in modulating SCD phenotype has been sparsely studied in African populations. In this cross-sectional study, we investigated the role of single nucleotide polymorphisms (SNPs) in iron-regulatory genes in SCD severity and lifetime transfusion(Tx) requirement. Methods: The study was approved by the institutional review board of Lagos University Teaching Hospital, Lagos, Nigeria. Clinical data were abstracted from medical records and patient interviews using a structured questionnaire. Participants were recruited in steady state and were stratified according to the severity score previously described by Shah et al. (Clinicoecon Outcomes Res. 2020;12:625). Biochemical analyses included serum transferrin and serum iron; transferrin saturation (TS) was calculated. Genotyping was performed using the Axiom Precision Medicine Research Array (PMRA; Thermo Fisher Scientific). Seventy-one single nucleotide polymorphisms (SNPs) in genes implicated in iron metabolism were analyzed, including SLC40A1 (ferroportin), HFE (homeostatic iron regulator), HJV (hemojuvelin), HAMP (hepcidin), and TFR2 (transferrin receptor 2). SNPs whose variants were not represented in this cohort, including HFE C282Y and H63D, were excluded. Ensembl and NCBI databases were used to describe the wild-type (WT)/variant alleles and gene consequences. Univariate and multivariate logistic regression were used to analyze binary outcomes, and age-adjusted linear regression for Tx burden. Odds ratios (OR) and regression coefficients (β) were estimated using the WT as the reference. Multiple-testing correction was performed as necessary. Statistical analyses were conducted in R version 4.4.1, with p&lt;0.05 considered significant. Results: We included 60 genotyped, confirmed HbSS patients; median age was 22 years (range: 18–43), 22 (37.3%) were female, 42 (70.0%) were classified as mild severity (Class I), 5 (8.0%) as Class II, and 13 (22.0%) as severe (Class III). Twenty-seven (45.0%) had never received a blood Tx, while 33 (55.0%) had received Tx, median of 2units (range: 1-10). On univariate analysis (UVA), five SNPs (rs10218795, rs10188230, rs114250626, rs4287798, and rs634349) were significantly associated with severe phenotype; three of these remained significant on multivariable analysis (MVA). Two were associated with higher odds of severe phenotype: rs10177654 (OR = 28.9, 95% CI: 3.0–100.0, p = 0.03) and rs10218795 (OR = 15.0, 95% CI: 2.4–327.0, p&lt;0.01), while rs10188230 was associated with lower odds (OR = 0.03, 95% CI: 0.008–0.28, p&lt;0.01). Results remained consistent after adjusting for age. For lifetime transfusion burden, both UVA and MVA identified two significant SNPs: rs4667289, associated with higher transfusion burden (β = 2.6, 95% CI: 0.04–5.2, p = 0.047) and rs11568344, associated with lower transfusion burden (β = –1.8, 95% CI: –3.5 to –0.36, p = 0.02). Genotype distributions for the five significant SNPs were as follows: rs10177654 (SLC40A1, transcription factor binding site), TT(WT) 12 (20.3%), TC 30 (50.8%), CC 17 (28.8%); rs10188230 (SLC40A1, intron variant), TT (WT) 32 (54.2%), TC 22 (37.3%), CC 5 (8.5%); rs10218795 (HJV, intron variant), CC (WT) 22 (37.3%), TC 29 (49.2%), TT 8 (13.6%); rs4667289 (SLC40A1 proximal intergenic), GG (WT) 46 (78.0%), AG 10 (16.9%), AA 3 (5.1%); rs11568344 (SLC40A1 splice region variant), GG (WT) 47 (79.7%), AG 9 (15.3%), AA 3 (5.1%). Compared with the homozygous WT, patients with rs10188230 had a lower median TS (21.65% vs. 43.3%, p = 0.04), while those with rs4667289 had a higher median TS (83% vs. 31%, p&lt;0.01). When adjusted for age and lifetime Tx, rs4667289 remained significant (β = 47.8, 95% CI 3.6-82.8, p = 0.03). No other SNPs showed association with TS. Conclusion: We present novel genetic data on iron-regulatory variants in African patients with sickle cell disease, identifying SNPs in SLC40A1 and HJV associated with disease severity. Most of these are yet to be fully described in the literature, and their intronic locations suggest possible regulatory roles. We hope to further validate these findings in larger cohorts and through functional studies to clarify their impact on iron metabolism and clinical significance.

Purpose Aneurysmal rupture and subarachnoid hemorrhage (SAH) have an exceptionally high mortality and morbidity burden. The aim of this study was to develop interpretable machine learning models for predicting short-term poor outcomes defined by the National Inpatient Sample Subarachnoid Hemorrhage Outcome Measure (NIS-SOM). Methods The National Inpatient Sample (NIS) database was queried from 2008 to 2018 to identify patients diagnosed with SAH who had undergone endovascular coiling or clipping for intracranial aneurysm. Demographic, comorbidity, risk factor, and hospital characteristic variables were recorded. Variables were preprocessed, and the feature space was reduced to include the most important features. To predict poor outcomes, machine learning models were trained and cross-validated before being evaluated on a separate testing set. Shapley Additive exPlanations of the best performing model was used for general and local model interpretation. Results Among 18,149 admissions (mean age 55 ± 14 years, 68.8% women), 52.9% had a poor outcome. Test-set AUCs ranged 0.74–0.80; a multilayer perceptron performed best (AUC 0.80, precision 0.74, recall 0.82). SHAP ranked the ten most influential variables: age, neurological comorbidity, paralysis, Medicare insurance, smoking status, Elixhauser burden, fluid-electrolyte disorders, weight loss, arrhythmia, and heart failure. Conclusions The modeling predicted nationwide aSAH prognosis with decent accuracy and highlighted clinical, socioeconomic, and system-level drivers of determinants of poor short-term outcome. These results support the potential of explainable ML tools as complementary tools for early risk stratification, guiding resource allocation, and informing prospective multi-center validation and implementation studies.

Abstract Objective Autoimmune encephalitis is a cause of brain inflammation characterized by auto‐antibodies, which target cell surface neuronal proteins and lead to neuronal dysfunction. The most common form is associated with auto‐antibodies to leucine‐rich glioma‐inactivated 1 (LGI1) protein, the presentation of which includes frequent focal seizures. The exact cause of these auto‐antibodies remains unknown, but established predispositions include overrepresented human leukocyte antigen ( HLA ) alleles. Yet, these HLA alleles are themselves common in the healthy ancestry‐matched population. One potential etiological hypothesis is that an environmental trigger, such as the gut microbiome, interacts with a genetically predisposed individual. Methods To investigate this, we studied 42 patients with LGI1‐antibody encephalitis (LGI1‐Ab‐E) and 27 familial/environmentally matched controls, and performed metagenomic shotgun sequencing, to describe the compositional and functional differences in the gut microbiome. Results We observed that LGI1‐Ab‐E gut microbiomes exhibited a significant reduction in the ratio of Firmicutes (or Bacillota) and Bacteroidetes phyla, which is associated with the dosage of HLA susceptibility allele count in patients with LGI1‐Ab‐E. Furthermore, we identified differences in functional gene profiles in the gut microbiome that led to a reduction of neuroinflammatory protective short‐chain fatty acids (SCFAs) in LGI1‐Ab‐E patients. Significance Taken together, our results suggest that a compositional shift in the gut microbiome of LGI1‐Ab‐E associates with a neuroinflammatory state, possibly through the reduction of SCFA production. Our study highlights the potential of the gut microbiome to explain some of the complex condition and unravel etiological questions. Validation studies with greater sample sizes are recommended.

Abstract Introduction Chronic obstructive pulmonary disease involves an unregulated inflammatory process that leads to the destruction and remodeling of lung architecture, potentially resulting in air-filled lesions known as bullae. We outline a novel technique for transbronchial decompression of a bulla using robotic-assisted bronchoscopy (RAB) in a patient with intraparenchymal emphysematous bullae. Case Description A 74-year-old woman with a medical history significant for COPD, Sjögren's disease, and former smoker, presented to our outpatient clinic with progressively worsening exertional dyspnea over the past two years. The patient underwent a thymectomy for thymic hyperplasia where a right middle bulla was incidentally identified. Posterior bullectomy was not performed intraoperatively due to severe pleural adhesions and the high risk of lung injury during dissection. High-resolution chest computed tomography revealed diffuse subpleural bullous changes, with asymmetric high-attenuation mural foci in several cysts (Figure 1A), with a total volume of 124.11 cm3. Given the high surgical risk, a bronchoscopic approach was decided. Bullae needle aspiration was performed under RAB guidance. Decompression was accomplished using PleurX catheter drainage (Pleur-Evac, Telfex, USA). The connection between the robot and the drainage system utilized a 3-way stopcock (Merit Medical Systems, USA) and a 30 cm vinyl connecting tube (Cook Incorporated, USA). Suction through water seal suction was performed at 20mmHg for 5 min, during which we observed bullae reduction with live intraprocedural mobile CT images. The robot was then retracted, and a 4.0 mm Zephyr endobronchial valve was deployed in the superior segment of the right middle lobe to promote atelectasis, no immediate complications were reported. Post-procedural chest CT demonstrated a significant reduction in bullae size as shown in Figure 1B. At the one-month follow-up, chest X-ray imaging revealed increased atelectasis and persistent collapse in the previously identified area of cystic change. By the two-month follow-up, pulmonary function tests indicated nonspecific ventilatory impairment, with improvements in FEV1% (from 70.5% to 78.2%) and FVC% (from 80.5% to 90.2% of the predicted values). Subsequent follow-ups have demonstrated clinical improvement in the patient's symptoms. Conclusion We contribute to the literature by introducing a novel, non-invasive technique for managing bullae with RAB in patients who are not candidates for surgery. Further studies are warranted to standardize this technique and assess its broader applicability. Figure 1. High-resolution computed tomography showing pre- and post-procedure views of the bullae. (A) Coronal and sagittal views showing the right middle lobe bullae. (66x81mm) (B) Post-procedure view of the chest HRCT (17x29 mm)