Citations

Abstract The sections in this article are: Why is Stress Distribution Nonuniform? Why is it Important to Know Stress Distribution? Simplifications Introduced to Analysis of Stress Distribution Relationship Between Microscopic Structure and Macroscopic Properties Material Properties of Lung Parenchyma Meaning of Other Elastic Constants Implications of Relative Magnitudes of Bulk and Shear Moduli Macroscopic Lung Stress Distribution Local Stress Distribution

Objective: To evaluate whether effects of oral hormone therapy (HT) on risks of venous and arterial vascular events differ by baseline statin or aspirin use. Methods: We performed time-to-event analysis using data from the Women’s Health Initiative menopausal HT randomized trials to assess risk of thrombotic events. Women were randomized to oral conjugated equine estrogens (CEEs) alone or placebo among women with prior hysterectomy (n = 10,739), and CEE with medroxyprogesterone acetate (MPA) or placebo among women with an intact uterus (n = 16,608), stratified by baseline personal use of statins and aspirin. We evaluated risk of prespecified, adjudicated thrombotic events, including coronary heart disease, stroke, venous thromboembolism, and/or composite major adverse cardiovascular events, at 2 and 5 years. Results: Baseline statin use (n = 827 in CEE-alone trial; n = 1,115 in CEE+MPA trial) or aspirin use (n = 2,212; n = 3,431) was limited. At 5-year follow-up, coronary heart disease risk for CEE-alone versus placebo was hazard ratio (HR) = 0.81 (95% CI: 0.44-1.49) in statin users, similar to nonusers, HR = 1.07 (95% CI: 0.82-1.40). For CEE+MPA, there was also no difference by statin use, HR = 1.02 (95% CI: 0.55-1.89) and HR = 1.47 (95% CI: 1.13-1.90), respectively. Neither statin nor aspirin exposure significantly modified effects of HT on any arterial or venous thrombotic outcome at 2 or 5 years. Conclusions: In this secondary randomized clinical trial analysis, neither statins nor aspirin significantly modified effects of oral HT on key arterial or venous thrombotic outcomes at 2 or 5 years. Results, however, may be underpowered given low baseline exposure prevalence for both statins and aspirin.

Background Mitral valve prolapse (MVP) can be associated with ventricular arrhythmias (VA), but little is known about the relationship between VA and exercise in these patients. The aim of this study was to assess the occurrence and severity of VA during exercise tests in patients with MVP, and to explore the association between VA during exercise and the occurrence of arrhythmic events during follow-up. Methods In this multicentre study, 375 patients with MVP (58 (48–69) years, 53% male) who underwent a clinically indicated exercise test were included. Severity of VA during exercise was defined as: (1) no VA, (2) minor VA (premature ventricular contractions ≥5% or non-sustained ventricular tachycardia (nsVT) <120 beats per minute) and (3) major VA (nsVTs ≥120 beats per minute). Results During exercise test, 242 (65%) patients showed no VA, 88 (24%) minor VA and 45 (12%) major VA. Patients with minor and major VAs showed more often bileaflet prolapse and mitral annular disjunction (MAD) than patients with no VA (p<0.001). Over a median follow-up of 101 months (IQR 58–138 months), 35 patients (9%) developed a severe arrhythmic event, defined as sustained VA or ventricular fibrillation, implantation of an implantable cardioverter-defibrillator and VA ablation. At the Kaplan-Meier curve analysis, patients with major VA showed the worst arrhythmic event-free survival (log-rank p<0.001). On multivariable analysis, left ventricular end-systolic diameter, MAD and VA severity during exercise were independently associated with this outcome. Conclusions In patients with MVP, the occurrence of VA during exercise is associated with more advanced mitral valve abnormalities, including MAD, and with higher rates of severe arrhythmic events during follow-up. Performing an exercise test, combined with the clinical and echocardiographic assessments, may therefore offer important complementary information useful for patient management.

Introduction: Excess sodium intake is strongly linked with hypertension and cardiovascular disease (CVD); people with narcolepsy (PwN) have increased CV risk. Hypothesis: Switching from high-sodium oxybate (SXB; Xyrem ® ; 6–9 g for ≥6 wks) to low-sodium oxybate (LXB; Xywav ® ; same regimen) reduces mean 24-hr ambulatory systolic blood pressure (ASBP) after ≈6 wks in PwN, regardless of antihypertensive (anti-HTN) use and site type. Methods: XYLO, an open-label, single-arm study (NCT05869773), assessed PwN aged 18−70 y with office SBPs of 130−155 mmHg. The primary and key secondary endpoints were changes from baseline (BL) to end-of treatment (EOT) in mean 24-hr ASBP and seated resting (“office”) SBP (OSBP), respectively; exploratory endpoints were diastolic BP (DBP) changes. Changes are baseline adjusted. Prespecified subgroup analyses explored BL anti-HTN use and participation site (ie, site-based [at study site] vs decentralized [at-home]). Results: In 43 PwN (mean age, 45 y; female, 65%; anti-HTN, 33%), mean±SD BL OSBP and DBP were 138.0±5.7 and 85.2±6.6 mmHg, respectively. Mean±SD total SXB vs LXB dosages were 8.0±1.1 vs 8.1±1.1 g/night, reflecting 1457±206 vs 118±16 mg sodium (difference: ≈1339 mg); median 24-hr urinary sodium was 4232 mg/d at BL and 2703 mg/d at EOT (median change: 1288 mg/d). Mean change in 24-hr ASBP (least squares mean [95% CI]) was −4.1 (−6.9, −1.4; 1-sided P =0.0019) mmHg (Fig 1) ; mean change in OSBP was −9.2 (−11.9, −6.5; 1-sided P <0.0001). Mean changes in 24-hr ambulatory and office DBP were −2.3 (−4.1, −0.5; 2-sided P =0.0118; nominal) and −3.8 (−6.0, −1.6; 2-sided P =0.0014; nominal) mmHg, respectively. In subgroups, mean change in 24-hr ASBP was −4.6 (−9.6, 0.3) mmHg with BL anti-HTN use and −3.9 (−7.3, −0.5) mmHg without BL anti-HTN use; changes in OSBP were −11.8 (−16.5, −7.1) and −7.9 (−11.1, −4.6) mmHg. Mean change in 24-hr ASBP was −3.6 (−8.0, 0.9) mmHg for site-based and −4.5 (−8.1, −1.0) mmHg for decentralized participation. Corresponding changes in OSBP were −9.0 (−13.3, −4.6; site-based) and −9.3 (−12.8, −5.8; decentralized) mmHg with a downward trend over 6 wks ( Fig 2 ). Treatment-emergent adverse events (all mild/moderate) occurred in 40% of PwN (N=67). Conclusions: Switching from SXB to LXB reduced daily medication-related sodium intake in PwN and was associated with clinically meaningful BP reductions overall and across subgroups, consistent with evidence on dietary and medication-related sodium effects.

Abstract Rationale Critically ill lung cancer patients are a growing, high-risk population. However, prognostic tools to guide intensive care unit (ICU) decision-making are limited. Objectives To identify oncologic and critical illness factors associated with 90-day mortality following ICU admission in patients with lung cancer. Methods We conducted a retrospective cohort study of lung cancer patients admitted to the ICU across Mayo Clinic Health System between 2018 and 2024. The primary outcome was 90-day mortality. Two complementary Cox proportional hazards models were developed: a focused model including cancer-specific variables (stage, time since diagnosis, time since last systemic therapy, prior thoracotomy, Eastern Cooperative Oncology Group [ECOG] performance status prior to admission, body mass index, cause of critical illness, code status at admission) and a full model that added broader clinical factors (age and Sequential Organ Failure Assessment [SOFA] score). We also evaluated discharge disposition and transitions in code status. Results Among 528 patients, 90-day mortality was 58.7%. In the focused model (C-index 0.67), independent predictors of mortality included late-stage disease, cancer-specific reason for ICU admission, limitations in resuscitation orders, and ECOG &gt;1. In the full model (C-index 0.95), only age and SOFA score remained significant. Among early-stage patients, recent targeted or combination therapy was associated with higher mortality, though this association may reflect underlying disease characteristics or treatment selection rather than direct treatment effects. Patients who changed code status during admission had high mortality (83%) and a low rate of discharge home (11%). Conclusion Lung cancer patients admitted to ICU experience high short-term mortality, with outcomes shaped by both oncologic status and the severity of acute illness. A dual-model approach suggests a risk hierarchy: Cancer-specific factors inform baseline mortality risk with an ICU admission, but age and physiologic derangement are the dominant drivers of survival once critical illness develops. These findings support dynamic, multidisciplinary prognostication and underscore the need to integrate oncology and critical care expertise in ICU decision-making.

Abstract Background Patients with pulmonary hypertension due to interstitial lung disease (PH-ILD) have worse exercise capacity and survival than ILD patients without PH. Vasoreactivity with inhaled nitric oxide (NO) provides prognostic and therapeutic implications in pulmonary arterial hypertension, but little is known about its value in PH-ILD. We evaluated the pulmonary hemodynamic changes following inhaled NO and their association with outcomes in PH-ILD. Methods We measured pulmonary hemodynamics in patients with PH-ILD who underwent inhaled NO administration during right heart catheterization. We recorded baseline clinical, echocardiographic, and pulmonary function testing measures, and investigated the use of inhaled treprostinil as well as the rate of hospitalization, death, and lung transplantation. Results In 120 patients (age 67 ± 11 years, 62% women), the administration of inhaled NO resulted in a median (IQR) decrease in mean pulmonary artery pressure (mPAP) of −3 (−5, −1) mmHg, P &lt; 0.001, and pulmonary vascular resistance (PVR) of −0.8 (−1.8, −0.2) wood units (WU), P &lt; 0.001. The % change in mPAP and PVR were −6.3 (−10.9, −1.8) % and −16.8 (−27.3, −3.3) %, respectively. Factors associated with the % drop in PVR included baseline PVR (r = 0.30, P &lt; 0.001), cardiac output (r = −0.19, P = 0.04), and WHO functional class (r = 0.25, P = 0.01). The median (IQR) follow-up was 14.5 (7, 25) months. During this time, 40 (33%) patients died, 8 (7%) underwent lung transplantation, and 76 (63%) experienced either hospitalization due to respiratory failure, transplantation, or death. The % drop in mPAP and PVR during inhalation of NO had no significant impact on these outcomes and was not associated with clinical response to inhaled treprostinil measured by changes in six-minute walk distance (6MWD) and forced vital capacity (FVC). Conclusion Inhaled NO caused a modest reduction in mPAP and PVR in patients with PH-ILD, but the acute hemodynamic response to inhaled NO was not associated with outcomes or response to inhaled treprostinil therapy.

Candida krusei empyema is a rare but serious manifestation of invasive candidiasis, characterized by intrinsic resistance to fluconazole, biofilm formation, and high mortality, with limited case-level data to inform management. This review aims to systematically identify and synthesize all reported English-language cases of Candida krusei empyema from January 2005 to June 2025 using PubMed, ScienceDirect, OVID MEDLINE, and Gale OneFile and perform descriptive analysis on them. Screening, data extraction, and eligibility assessment were performed, and those articles not clearly meeting eligibility criteria were reviewed by additional reviewers with consensus resolution. Seven publications (six individual cases and two cohorts) were included. We additionally describe the clinical course, management, and outcome of a 70-year-old bilateral lung transplant patient who developed persistent C. krusei empyema despite optimized antifungal therapy. Patients ranged from 11 to 74 years of age (median 62.5 years). Predisposing factors included esophageal perforation (n = 4), post-transplant hemorrhage (n = 1), community-acquired empyema (n = 1), and thoracic surgery (n = 1). Empiric fluconazole was switched to caspofungin (3/4), with others receiving amphotericin B, voriconazole, or combination therapy. Source control varied: chest tube drainage (n = 3), percutaneous catheter (n = 3), and surgical decortication (n = 2). Mortality was 14.3% (1/7). In the absence of clear guidelines and robust literature, the management approach remains heterogeneous. Optimal care requires early recognition, aggressive multimodal antifungal therapy, and effective source control tailored to patient risk. Standardized antifungal protocols and larger case series are needed to guide clinicians in managing this challenging infection.

BACKGROUND: People with narcolepsy are at increased risk for hypertension and cardiovascular disease; excessive sodium intake is linked to both. METHODS: We studied patients with narcolepsy and office systolic blood pressures (BPs) of 130 to 155 mm Hg taking twice-nightly high-sodium oxybate for ≥6 weeks who switched to low-sodium oxybate at the same dosage. The primary end point was the change from baseline in mean 24-hour ambulatory systolic BP at the end of treatment (≈6 weeks after switching). Secondary and exploratory end points included changes in diastolic BP, office BP, and 24-hour sodium excretion. RESULTS: Patients (n=43) had a mean age of 45 years, were 65% female, 33% on antihypertensives, with baseline mean (SD) office BP of 138.0/85.2 (5.7/6.6). Mean (SD) total high- and low-sodium oxybate dosages of 8.0 (1.1) and 8.1 (1.1) g/night, respectively, represented 1456.5 (206.2) and 117.8 (16.3) mg of sodium. The median 24-hour urinary sodium was 4278 mg/d at baseline and 2703 mg/d at the end of treatment (median change, 1288 mg/d). Mean (SE) 24-hour ambulatory systolic BPs at baseline and study end were 132.3 (1.8) and 128.2 (1.8) mm Hg (least-squares mean change, −4.1 [95% CI, −6.9 to −1.4] mm Hg; 1-sided P =0.0019). BP changes by narcolepsy subtype, sex, body mass index, baseline office BP, and baseline antihypertensive use were consistent with the overall effect size. CONCLUSIONS: People with narcolepsy switching from high- to low-sodium oxybate showed substantially reduced daily medication-related sodium intake and significant 24-hour BP reductions. These results demonstrate the importance of reducing pharmaceutical sodium content in this elevated cardiovascular risk patient population. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05869773.