Background: Idiopathic inflammatory myopathies (IIMs) are a heterogenous group of disorders frequently complicated by interstitial lung disease (ILD). We sought to discern phenotypic and serological differences according to the presence of ILD and initial evaluating medical specialty, i.e., rheumatology vs. pulmonology, with the goal of advancing personalized medicine. Methods: A computer-assisted search was conducted to identify patients with a diagnosis of IIM seen at Attikon University Hospital, from January 2010 to December 2025. Medical records were reviewed for clinical, laboratory and serological features. Results: We identified 140 patients with IIM; 96 (68.6%) were female with a mean age at diagnosis of 55.8 years (SD 15.7). ILD was present in 75 patients (53.6%), being more common among males (30/44, 68.2% vs. 45/96 females, 46.9%, p = 0.019). Patients in the ILD subgroup were older at diagnosis (mean age 60.2 years vs. 50.7 years, p < 0.001) and presented more often with dyspnea (41 vs. 1, p < 0.001), higher CRP (median 5.95 mg/L vs. 2.9 mg/L, p = 0.024), and lower CPK (median 103 vs. 580, p < 0.001). Patients first seen by a pulmonologist were more likely to be older (mean age 60.5 years vs. 53 years, p = 0.002) and to present with dyspnea (33 vs. 9, p < 0.001) and ILD (48 vs. 27, p < 0.001). By contrast, skin involvement (61% vs. 27%, p = 0.04), muscle weakness (53 vs. 15, p < 0.001) and elevated CPK (median 301.5 vs. 103.5, p = 0.013) were less frequent in these patients as compared to patients first evaluated by a rheumatologist. Anti-tRNA synthetase, anti-Ro52 and anti-Pm/Scl antibodies were more frequent in the ILD subgroup. Anti-tRNA antibodies were also more frequent in patients first seen by a pulmonologist. Conclusions: Patients with IIM-ILD are more likely to present without overt clinical or biochemical characteristics of muscle involvement, thereby increasing the likelihood of initial evaluation by pulmonologists.
Aims: To assess the spatiotemporal stability of extra-pulmonary vein (PV) sources in patients with persistent atrial fibrillation (AF). Methods and results: Nine patients (mean age 63 ± 9 years, 55% male) with persistent AF were included who underwent an initial and at least one redo catheter ablation procedure utilizing panoramic atrial mapping (PAM) systems (CardioInsight, electrographic flow (EGF), and/or charge density (CDM) mapping). Procedures were performed in the following combinations: CDM-CDM (1 patient), CDM-EGF (1 patient), EGF-CDM (3 patients), CardioInsight-CDM (1 patient), EGF-EGF (3 patients). We reviewed maps and analyzed the location of AF sources. Spatiotemporal stability was defined as the presence of an AF source of identical location on available maps during the initial and the redo procedure. In 4 patients (44.4%), localization of AF sources mapped at the repeat procedure corresponded with the localization of sources mapped during the index procedure. In two patients, no sources were identified during the second procedure. In the remaining 3 patients, the localization of sources was detected at different locations. Conclusions: Our findings suggest the presence of spatiotemporal stability of AF sources; however, novel sources can also be found during the repeated procedure, consistent with disease progression.
Mucopolysaccharidosis (MPS) are a group of inherited lysosomal storage genetic disorders that affect the body's ability to break down glycosaminoglycans (GAGs) due to the deficiency of required enzymes. This leads to depositions of these GAGs in various tissues and organs resulting in multi-systemic manifestations including pulmonary and sleep related issues. In recent years, there have been significant advancements in therapeutic options and supportive management which have led to the overall improvement in respiratory care, culminating in improved quality of life for MPS patients. Management of pulmonary and sleep disorders in mucopolysaccharidosis requires a multidisciplinary approach due to the multi-systemic affectation of the genetic disorders. Therapeutic options such as enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) have yielded varying success in mitigating respiratory complications. Emerging treatments such as gene therapies have shown exciting and promising results thus far. Supportive therapies such as airway clearance, regular vaccination and use of positive airway pressure devices are also essential. Pre-operative airway and anesthesia planning is critical to mitigate peri-operative and post-operative complications. Early diagnosis, close monitoring and a patient focused individualized approach are essential for respiratory optimization and overall improvement in clinical outcomes. This review article aims to discuss these advancements in a comprehensive format, making it accessible to medical providers who care for this subset of patients.
Background: Ventricular septal defects (VSD) are the most common form of congenital heart disease (CHD). Current guidelines recommend surveillance transthoracic echocardiograms (TTE) following surgical closure of perimembranous VSDs (pVSD); however, duration of screening is not explicitly stated. The goal of this study is to determine the utility of follow-up TTEs after uncomplicated pVSD surgical closure. Methods: Single-site retrospective analysis was conducted on patients who underwent pVSD surgical closure. Patients were excluded if diagnosed with other CHD, had complications 1 year post-repair, or lacked data 1 year post-repair. Serial TTEs were reviewed. A Kaplan-Meier curve was used to illustrate the 5-year complication-free survival. Results: A total of 117 patients met inclusion criteria. A 97% 5-year complication-free survival was observed. Four patients had complications >1 year post-repair: one non-obstructive subaortic ridge, one pulmonary vein stenosis, one pinhole residual pVSD, and one ventricular ectopy with ventricular dysfunction. Of the 113 complication-free patients, 197 TTEs were performed with no change in clinical management. Conclusions: Beyond 1 year post-repair, the occurrence of new complications following uncomplicated pVSD surgical closure is rare. Unless clinical concerns arise, the utility of routine TTEs > 1 year post-repair in this uncomplicated post-surgical cohort should be reassessed. Larger multicenter studies are needed to determine the utility of routine TTEs.
Objective: Rapid assessment of early treatment-related physiological improvement in emergency department (ED) patients with respiratory failure (RF) remains challenging. Blood gas analysis is informative but invasive and not ideal for repeated use. The vertical displacement index (VDI), an ultrasound-derived parameter based on pleural motion, may provide dynamic bedside information on early physiological change. This study evaluated whether changes in VDI are associated with early physiological improvement in ED patients with RF. Methods: This prospective observational study was conducted in the EDs of two tertiary care hospitals. Adult patients presenting with dyspnea and clinical evidence of RF were included. VDI was measured by lung ultrasound at baseline and 30 min after initial treatment. The primary endpoint was the change in VDI 30 min after the initial treatment, calculated as the difference between pre-treatment and post-treatment VDI. The expected direction was a post-treatment decrease in VDI, with greater VDI reduction expected to be associated with greater early physiological improvement. Secondary analyses included comparisons of VDI changes across oxygen saturation and diagnostic groups, as well as correlations between ΔVDI and physiological changes. Patients were grouped by admission oxygen saturation (<80%, 80-90%, and ≥90%). Results: Seventy-nine patients were included. Pre-treatment VDI differed significantly between oxygen saturation groups, with the highest values in the most hypoxemic patients (p = 0.028). VDI decreased significantly after treatment in all groups (p < 0.001 for all), with the greatest reduction in the <80% group. By diagnosis, VDI decreased significantly in pulmonary edema, COPD/asthma, and pneumonia, but not in pulmonary embolism (p = 0.138). VDI reduction correlated positively with improvements in oxygen saturation (r = 0.27, p = 0.016) and pH (r = 0.24, p = 0.037), but not with CO2. Conclusions: VDI may be explored as a practical ultrasound-derived bedside parameter associated with early physiological improvement in ED patients with RF.
Diabetic patients face increased severity in viral respiratory infections, yet during the longitudinal progression of lung recovery, the radiological clearance is poorly quantified. This prospective study at an infectious diseases hospital analyzed 430 patients with confirmed viral pneumonia. Radiological severity (Rx) and pleural effusion were scored (0-3) at admission (day 1) and follow-up (day 6). Diabetics presented with significantly higher baseline severity (Median 2.0 vs. 1.0, p < 0.0001). While both groups improved at identical rates (Median Δ = -1.0), a significant radiological lag persisted in diabetics at day 6 (Median 1.0 vs. 0.0, p < 0.0001). Attrition analysis (N = 75) revealed a divergent lethal split: attrition in the non-diabetic cohort was almost exclusively driven by low-severity early departures against medical advice (94.2%), whereas diabetic attrition was primarily characterized by early mortality (60.9%; p < 0.0001). Although the diabetic state was associated with a pronounced radiographic resolution delay in unadjusted comparisons, this disadvantage was substantially attenuated and lost statistical significance after adjustment for admission radiological severity (adjusted OR 2.04, 95% CI 0.88-4.76) and chronic comorbidity burden (adjusted OR 1.37, 95% CI 0.56-3.39), indicating that the diabetic lag is largely explained by a higher presenting severity and comorbidity burden rather than by an independent acute effect of diabetes itself. Sensitivity analyses suggest that the observed lag in survivors likely underestimates the true disease burden, given the concentration of early mortality among high-risk diabetic cases.
Intraoperative mobile CT (iCT) and virtual-assisted lung mapping (VAL-MAP) are used to localize pulmonary nodules that are difficult to palpate during minimally invasive surgery. Because these techniques differ in workflow structure and timing of image acquisition, their operative time and radiation exposure may differ. We aimed to describe workflow characteristics and radiation exposure associated with newly implemented iCT and to contextualize these findings against our established VAL-MAP practice. We retrospectively reviewed 50 consecutive patients who underwent thoracoscopic wedge resection with localization between January 2024 and December 2025. Twenty-four underwent iCT-guided localization using an O-arm system, and 26 underwent VAL-MAP with bronchoscopic dye marking followed by post-mapping CT. Technique selection was based on device availability and surgeon discretion. CT dose metrics and time components related to localization were analyzed. Median CT-related dose-length product (DLP) was higher in the iCT group, primarily due to high-definition scans. When performed in standard mode with a limited scan frequency, iCT radiation exposure approximated that of post-VAL-MAP CT. Preparation CT after lateral positioning reduced repeat scans and iCT-related interruption time. Anesthesia and operative times were shorter in the VAL-MAP cohort, reflecting localization outside the operating room. Overall procedural burden appeared modestly different. Our single-center retrospective study quantified the total procedural time for VAL-MAP and iCT, finding modest differences in time and radiation exposure. These real-world data aid institutions considering these localization strategies, but do not establish superiority. Definitive comparative conclusions require future prospective evaluations controlling for nodule characteristics and cost.
(1) Background: Indonesia faces the dual challenge of a high tuberculosis (TB) burden and increasing drug resistance. Conventional molecular diagnostics frequently fail to detect isoniazid resistance and nontuberculous mycobacteria (NTM). This study evaluates a domestic multiplex Open PCR system in Medan, Indonesia. (2) Methods: From July to November 2025, 1569 sputum specimens from suspected TB patients were analysed using the Indigen MTB/NTM/DR-TB Real-time PCR Kit Gen 2. (3) Results: Mycobacterial DNA was detected in 421 specimens (26.8%). Among these, 396 (94.1%) were drug-susceptible TB, while 16 (3.8%) showed resistance, predominantly INH mono-resistance (n = 14; 0.89% of total). Additionally, 9 cases (2.1%) involved NTM or TB-NTM co-infections. Tertiary hospitals showed significantly higher positivity rates (33.5%) than primary care (18.9%; p < 0.001). TB status was significantly associated with male (p = 0.0052) and older age (p = 0.006), whereas resistance profiles and NTM distribution were consistent across all demographic groups (p > 0.80). (4) Conclusions: This study describes the implementation and diagnostic yield of a domestic multiplex Open PCR system in Medan, Indonesia. By bridging diagnostic gaps across a decentralized referral network, this facilitates rapid and targeted therapy. Integrating multiplex domestic innovations into national diagnostic algorithms is essential for achieving Indonesia's TB elimination targets.
Pulmonary fibrosis, particularly idiopathic pulmonary fibrosis (IPF), is a chronic and progressive interstitial lung disease characterized by alveolar epithelial injury, fibroblast activation, and excessive extracellular matrix deposition, which collectively lead to respiratory failure. Despite the availability of antifibrotic agents, disease-modifying therapies remain limited. Emerging evidence has identified dysregulated sphingolipid metabolism, especially ceramide accumulation, as a key driver of fibrotic pathogenesis. Ceramide is a central bioactive lipid in the sphingolipid pathway that regulates multiple cellular processes, including apoptosis, inflammation, endothelial barrier dysfunction, and fibroblast activation, all of which contribute to pulmonary fibrosis. This review is a narrative review that systematically summarizes the biosynthetic and metabolic pathways of ceramide, with an emphasis on chain length-specific functions and the ceramide to S1P rheostat. We further discuss the mechanistic roles of ceramide in alveolar epithelial cell apoptosis, inflammatory responses, and vascular barrier disruption in fibrotic lung disease. Finally, we highlight emerging therapeutic strategies that target ceramide metabolism, including inhibitors of acid sphingomyelinase (ASMase) and serine palmitoyltransferase (SPT), and propose future directions for clinical translation.
Pulmonary arterial hypertension (PAH) is a fatal vascular disorder with poor prognosis. 6:2 chloro-polyfluorooctane ether sulfonate (F-53B), a persistent environmental contaminant detected in humans, is known to be vasculotoxic, yet its association with PAH remains unexplored. This study aims to elucidate the mechanisms linking F-53B exposure to PAH by integrating network toxicology, molecular docking and in vitro experiments. Potential F-53B targets were predicted using ChEMBL, PharmMapper, and TargetNet. PAH-related genes were compiled from GeneCards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), and GSE254617. We identified 42 key targets of F-53B-related PAH. Functional enrichment revealed terms such as inflammatory response and extracellular matrix. Protein-protein interaction (PPI) analysis identified five hub genes: CCL2, CXCL8, CCL5, CCR2, and CCL11. Molecular docking confirmed strong binding between F-53B and these core targets, with CCR2 showing the strongest affinity (-10 kcal/mol). Molecular dynamics simulations further verified stable binding to CCR2. In vitro experiments demonstrated that F-53B activated the CCL2/CCR2 axis and induced IL-1β, TNF-α, and IL-6 in HUVECs and RAW264.7 cells. This study reveals that F-53B is linked to PAH through dysregulation of chemokine signaling networks and induction of inflammatory cytokines. These findings suggest F-53B as a potential environmental risk factor for PAH and pinpoint potential targets for intervention.
Objective: The present study aimed to determine clinical and surgical variables associated with postoperative morbidity and 10-year mortality in isolated mitral valve replacement (MVR) and to assess the association between sex and postoperative outcomes. Materials and Methods: A total of 1629 patients undergoing isolated MVR in one center during the period between January 2000 and December 2015 were retrospectively analyzed. Hospital records provided demographic, clinical, echocardiographic, and operative data. Cox regression analyses were used to determine factors associated with postoperative morbidity and long-term mortality. The Kaplan-Meier method was used to analyze long-term survival, and the log-rank test was used to compare the groups. Results: A total of 866 (53.1%) patients were male and 763 (46.9%) were female, and the average age was 63.8 ± 10.9 years. There were no significant differences in female and male patients regarding basic demographic and clinical characteristics. The first 30-day in-hospital morbidity rate was also significantly greater in women than in men (25.7% vs. 20.6%; p = 0.015). The in-hospital mortality was more prevalent among women (5.0% vs. 3.0%; p = 0.043). Age, sex (female), diabetes mellitus, pulmonary hypertension, chronic obstructive pulmonary disease, critical preoperative condition, high body mass index, longer cardiopulmonary bypass time, and low left ventricular functioning were significantly associated with postoperative morbidity in multivariable analysis. The total mortality rate during a 10-year follow-up was 33.2%, which was considerably higher among women compared to men (36.3 vs. 30.5; p = 0.013). Kaplan-Meier analysis demonstrated significantly lower long-term survival in female patients (log-rank p = 0.011). Conclusions: Morbidity and mortality following isolated MVR are closely related to patient-related factors. Female sex showed a significant adjusted association with higher 10-year mortality in multivariable analysis, warranting careful long-term risk assessment in female patients.
Background: Cancer-Related Fatigue (CRF) significantly impairs physical performance and quality of life (QoL) in patients with non-small-cell lung cancer (NSCLC). The OVER-CRF study evaluated the feasibility, safety, and preliminary efficacy of a personalized pulmonary rehabilitation (PR) program combining supervised exercise and education during active treatment. Methods: Patients with stage II-III NSCLC were randomized to Early-PR (initiated at the start of anticancer therapy) or Delayed-PR (initiated three months later). The 3-month intervention included two educational sessions and eight supervised exercise sessions. The primary outcome was adherence; secondary outcomes included safety, CRF (FACIT-FS), QoL (EORTC-QLQ-C30), and physical performance (6MWT). Results: Thirty-one patients were randomized (mean age 67.4 years). Adherence was excellent (Early: 86.7%; Delayed: 91.7%), exceeding feasibility thresholds. No exercise-related adverse events occurred. At 12 months, 50% of participants showed clinically meaningful CRF improvements. While both groups improved 6MWT performance during the intervention, the Delayed-PR group demonstrated more sustained QoL improvements from T1 through T3 compared to the Early-PR group. The dropout rate (25.8%) was consistent with the existing literature. Conclusions: Personalized PR is feasible and safe for NSCLC patients undergoing multimodal therapy. While early intervention provides immediate benefits, initiation timing may influence long-term QoL trajectories. These findings support integrating exercise and education into standard oncological care pathways.
Background: Systemic sclerosis (SSc) is an autoimmune disease with interstitial lung disease (ILD) representing the leading cause of mortality. Diaphragmatic muscle impairment, which may contribute to respiratory dysfunction, is underexplored in SSc. Objective: This study aimed to assess diaphragmatic thickness using HRCT in patients with SSc-ILD and to investigate whether this parameter correlates with disease severity and clinical outcomes. Methods: We conducted a multicentric retrospective observational study that included 161 participants: 69 with SSc-ILD and 92 matched controls without pulmonary disease. Preliminary findings from this cohort were previously communicated as a conference abstract at EULAR 2024. Diaphragmatic thickness was measured on axial and coronal CT images at the celiac axis level by two independent radiologists. Clinical and functional parameters were collected, including forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO), echocardiographic findings, and 6 min walking test performance. Results: The left hemidiaphragm was significantly thinner in patients with SSc-ILD compared with controls (2.98 ± 1.04 mm vs. 3.44 ± 0.97 mm; p = 0.004), while the right hemidiaphragm showed a non-significant trend toward reduction (3.21 ± 1.09 mm vs. 3.52 ± 1.05 mm; p = 0.072). Thinning of the right hemidiaphragm correlated significantly with lower FVC (p < 0.05). ROC analysis identified an optimal left diaphragm cut-off of ≤3.115 mm (AUC = 0.635, 95% CI: 0.556-0.709, sensitivity = 66.7%, specificity = 60.9%). No associations were found with the autoantibody profile, disease duration, or treatment. Interobserver reliability was excellent (Bland-Altman mean difference -0.002 mm, p = 0.95). Conclusions: HRCT-measured left hemidiaphragm thickness is significantly reduced in patients with SSc-ILD compared with controls, and right hemidiaphragm thickness correlates with impaired lung function. Although its discriminative performance is modest (AUC 0.635), this parameter may serve as a supplementary zero-burden addition to routine HRCT evaluation alongside pulmonary function tests. The retrospective cross-sectional design precludes conclusions about causality or prognosis; prospective studies incorporating concurrent functional diaphragm assessment are warranted.
Background and Clinical Significance: IgG4-related disease (IgG4-RD) is a chronic fibroinflammatory, immune-mediated multisystem disorder that can mimic neoplastic, infectious, or autoimmune conditions. Among its head-and-neck manifestations, IgG4-related dacryoadenitis and sialadenitis, historically referred to as Mikulicz disease, should be distinguished from the classical Mikulicz syndrome, which describes secondary lacrimal and salivary gland enlargement due to other systemic disorders. Renal involvement, most commonly in the form of IgG4-related tubulointerstitial nephritis (IgG4-TIN), is less frequent but carries major prognostic implications because delayed diagnosis may lead to irreversible kidney damage. Case Presentation: A 49-year-old man with no relevant past medical history presented with a 2-year history of intermittent polyuria and foamy urine. Laboratory testing revealed advanced kidney dysfunction, with serum creatinine of 4.2 mg/dL, estimated glomerular filtration rate of 16 mL/min/1.73 m2, and proteinuria of 2874 mg/day. Physical examination showed bilateral parotid enlargement, upper eyelid edema, lacrimal gland enlargement, and sicca symptoms, raising suspicion for IgG4-related dacryoadenitis and sialadenitis (Mikulicz disease). Further work-up demonstrated marked eosinophilia, polyclonal hypergammaglobulinemia, and significantly elevated serum IgG4 levels (3180 mg/dL), while infectious serologies and autoimmune studies were negative. Kidney biopsy revealed plasma cell-rich tubulointerstitial nephritis with lymphoplasmacytic and eosinophilic infiltrates, interstitial fibrosis, tubular atrophy, and more than 40 IgG4-positive plasma cells per high-power field, supporting the diagnosis of IgG4-related tubulointerstitial nephritis in the setting of systemic IgG4-RD. Treatment with prednisone followed by mycophenolate mofetil led to improvement in glandular manifestations and a partial reduction in proteinuria, but renal recovery remained incomplete. The patient subsequently developed a severe pulmonary infection complicated by sepsis and oligoanuric acute kidney injury superimposed on chronic kidney disease, and ultimately progressed to end-stage kidney disease requiring chronic maintenance hemodialysis. Conclusions: This case highlights that a Mikulicz disease phenotype may represent the initial manifestation of systemic IgG4-RD and should prompt evaluation for extraglandular involvement, particularly renal disease. In patients with glandular enlargement, eosinophilia, hypergammaglobulinemia, and unexplained renal dysfunction, IgG4-RD should be actively considered. Kidney biopsy remains essential for diagnostic confirmation and prognostic assessment, as delayed recognition may result in irreversible renal damage and progression to end-stage kidney disease.
Psoriasis is a chronic systemic inflammatory disease associated with increased cancer risk; however, its relationship with colorectal cancer (CRC) remains unclear. This question is particularly relevant in Asia, where CRC incidence has been increasing rapidly in recent decades. We conducted a nationwide longitudinal cohort study using the Korean National Health Insurance Service-National Sample Cohort (2002-2019). Patients with psoriasis were identified using validated ICD-10 codes and matched 1:4 with controls by age, sex, income, and region. Propensity score overlap weighting was applied to achieve covariate balance. Incident CRC was defined using both ICD-10 codes and cancer-specific registration codes. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 16,670 patients with psoriasis and 66,680 matched controls were included. During follow-up, the incidence of CRC was comparable between the two groups. In the weighted model, psoriasis was not associated with an increased risk of CRC (aHR = 0.96; 95% CI: 0.83-1.10). Kaplan-Meier analysis showed no significant difference in cumulative incidence (log-rank p > 0.05). Subgroup analyses stratified by age, sex, income, region, and comorbidity burden yielded consistent null findings. In this large nationwide cohort, psoriasis was not associated with an increased risk of CRC. These findings suggest that psoriasis does not independently contribute to CRC risk at the population level and does not warrant additional CRC surveillance beyond established screening recommendations, even in a high-burden setting such as Korea.
Cigarette smoke is a major inducer of oxidative stress, promoting reactive oxygen species (ROS) accumulation and contributing to the pathogenesis of chronic obstructive pulmonary disease (COPD) and lung cancer. Heated tobacco products (HTP) and e-cigarettes are promoted as reduced-risk alternatives; however, their impact on cellular redox regulation remains unclear. Here, we investigated the effects of conventional cigarette smoke extract (CSE), HTP, and e-cigarette extracts on hydrogen peroxide (H2O2) permeability mediated by aquaporins (peroxiporins) and on the activity of key antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) in ATII-like cells. Eight aquaporins were detected at the mRNA level, and seven were confirmed at the protein level. CSE markedly inhibited H2O2 permeability across plasma, mitochondrial, and nuclear membranes. HTP extract impaired H2O2 transport across the plasma membrane and nuclear envelope, while mitochondrial permeability was preserved. Both CSE and HTP extract reduced superoxide dismutase and glutathione peroxidase activities. In contrast, e-cigarette extract exerted minimal effects on membrane H2O2 permeability and selectively decreased superoxide dismutase activity. Overall, our findings identify a graded pattern of oxidative toxicity (CSE > HTP > e-cigarette) and highlight peroxiporins as critical regulators of intracellular redox homeostasis. Although less harmful than cigarettes, alternative nicotine delivery systems are not biologically inert.
Hospital quality reporting remains a manual, costly process with critical limitations as a mechanism to improve care outcomes. To assess whether near-real-time quality measurement, enabled by large language models (LLMs), can improve quality performance as measured by the Centers for Medicare & Medicaid Services (CMS) Severe Sepsis and Septic Shock Management Bundle (SEP-1) quality metric. This single-blind, unstratified, cluster randomized trial was conducted between December 13, 2024, and July 8, 2025, at 2 academic emergency departments (EDs) within the University of California, San Diego (UCSD) health system. Participants included all 66 attending physicians who practiced in the UCSD EDs and worked more than 3 shifts per month prior to study initiation. Participants were randomized to receive targeted feedback from LLM-determined compliance with SEP-1 at the time of patient discharge or standard process. The primary outcome was overall compliance with SEP-1. Secondary outcomes included expert agreement with the LLM SEP-1 determination, 30-day mortality, and intensive care unit admissions of patients with severe sepsis and/or septic shock in the ED. Effect sizes were estimated from a mixed-effects logistic regression model with the intervention group as a fixed effect and a random intercept for physician. The study population included 66 physicians who treated 301 patients (121 in the control group and 180 in the intervention group; median age, 64.3 [IQR, 51.1-75.7] years; 171 [56.8%] male; 52 [17.3%] with chronic kidney disease; 52 [17.3%] with chronic heart failure) who met CMS inclusion criteria for SEP-1. Physicians in the control group had a SEP-1 compliance rate of 70.1%, while those in the intervention group had a rate of 82.9%. Assignment to the intervention group resulted in a 13.0% absolute improvement in SEP-1 compliance (95% CI, 2.5%-23.4%; odds ratio, 2.10 [95% CI, 1.15-3.81]; P = .02) in the mixed-effects model. The largest difference between the intervention group and control group was in noncompletion of the 30-mL/kg fluid bolus component (3 of 180 [1.7%] vs 16 of 121 [13.2%]), a documentation-sensitive component of the quality measure. Agreement between LLM determination and expert review was 92%. No significant differences existed in intensive care unit admissions or 30-day mortality. In this cluster randomized trial of artificial intelligence (AI)-enabled medical record abstraction for sepsis care, rapid assessment of SEP-1 performance and targeted feedback improved overall compliance with the measure. AI-driven quality clinical integration may address limitations in existing hospital quality reporting and better support a learning health system. ClinicalTrials.gov Identifier: NCT07581340.
Pulmonary arterial hypertension (PAH) is a rare and progressive disorder characterized by increased pulmonary vascular resistance and vascular remodeling. Genetic polymorphisms, epigenetic modifications, and ion channel dysregulation are increasingly recognized as key contributors to disease pathogenesis. Anoctamin-1 (ANO1/TMEM16A), a calcium-activated chloride channel, plays a critical role in vascular tone regulation. This study aimed to investigate the association between ANO1 gene polymorphisms (rs7127129 and rs2509153), promoter methylation status, and serum chloride levels in patients with idiopathic pulmonary arterial hypertension (IPAH), congenital heart disease (CHD), and chronic thromboembolic pulmonary hypertension (CTEPH). A total of 106 IPAH patients, 40 CHD patients, and 30 CTEPH patients, together with 125 healthy controls, were included. The control group had a comparable age distribution, with a balanced sex ratio, whereas females predominated in all three PH groups. Genotyping was performed using TaqMan-based real-time PCR. Promoter methylation was analyzed using bisulfite conversion followed by quantitative real-time PCR. Serum chloride levels were measured using an ion-selective electrode method. No significant association was observed between rs7127129 and rs2509153 polymorphisms and IPAH or CTEPH (p > 0.05). However, rs7127129 showed a significant association with CHD (p < 0.05). After excluding hypertensive patients, both polymorphisms remained significantly associated with CHD. Serum chloride levels differed significantly among groups (p < 0.001), with higher levels observed particularly in the CTEPH and CHD groups compared to controls, while IPAH patients exhibited intermediate but still elevated levels relative to controls. In contrast, promoter methylation levels were significantly lower in all patient groups compared to controls. An inverse relationship between chloride levels and methylation status was observed. ANO1 polymorphisms are not major determinants of IPAH or CTEPH but may contribute to CHD susceptibility. Increased serum chloride levels, together with decreased promoter methylation, suggest a potential mechanistic link between ion channel dysregulation and epigenetic alterations in pulmonary hypertension. Further large-scale and functional studies are warranted.
Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease that occurs due to fibrotic remodeling of the pulmonary vessels. This leads to increased pressure overload onto the right ventricle, resulting in complications such as heart failure. Pulmonary endarterectomy (PEA) remains the gold standard of treatment for CTEPH, yet many patients experience life-threatening perioperative complications, including refractory right ventricular failure, reperfusion pulmonary edema, and endobronchial hemorrhage. Extracorporeal membrane oxygenation (ECMO) has been used as a form of mechanical circulatory support to aid recovery in patients with perioperative complications in the context of CTEPH. This review identifies preoperative risk factors, including pulmonary vascular resistance, high body mass index, and elevated neutrophil-to-lymphocyte ratios. It also identifies differences in ECMO configuration, with veno-arterial ECMO preferred for hemodynamic instability and veno-venous ECMO for respiratory failure. Finally, we posit that, based on contemporary literature, the implementation of early ECMO in decompensated patients may be associated with reduced hospital mortality, and in those who survive beget excellent mid-term survival.
To evaluate efficacy and safety of high-flow nasal cannula (HFNC) versus noninvasive ventilation (NIV) in adults with hypercapnic respiratory failure (HRF). We conducted a meta-analysis of randomized controlled trials from PubMed, Embase, The Cochrane Library, Wanfang, CNKI, and Weipu comparing HFNC with NIV in HRF patients. Primary outcomes were mortality and endotracheal intubation. Secondary outcomes included blood gas values, hospital/ intensive care unit (ICU) length of stay, nasal skin breakdown, and comfort. Pooled risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) were calculated. Twenty trials involving 1835 patients were included. No significant differences were observed in mortality (RR, 0.94; 95% CI, 0.69 to 1.28), endotracheal intubation (RR, 0.87; 95% CI, 0.71 to 1.06), PaCO2 (MD, -0.87 mmHg; 95% CI, -2.98 to 1.25) or PaO2 (MD, 2.67 mmHg; 95% CI, -0.66 to 6.01). However, HFNC significantly reduced hospital stay (MD, -0.69 days; 95% CI, -1.08 to -0.30) and ICU stay (MD, -0.98 days; 95% CI, -1.50 to -0.45), lowered nasal skin breakdown risk (RR, 0.20; 95% CI, 0.09 to 0.45) and improved comfort (MD, -1.19; 95% CI, -1.98 to -0.41). Subgroup and sensitivity analyses confirmed the principal findings. HFNC was not significantly different from NIV for mortality and endotracheal intubation in HRF but was associated with shorter hospital and ICU stays, reduced nasal facial skin breakdown and improved comfort. Larger trials in diverse populations are needed.