Cystic fibrosis (CF) airway disease is characterized by exaggerated inflammatory responses and progressive respiratory failure. Although interleukin-8 (IL-8) is a central mediator of neutrophilic inflammation in the CF airway, the upstream epithelial pathways that regulate cytokine production remain incompletely understood. Interleukin-17C (IL-17C) is an epithelial-derived IL-17 family cytokine that can promote inflammatory signaling in an autocrine/paracrine manner, but its regulation in CF-derived airway epithelial cells remains poorly defined. Here, we examined Toll-like receptor (TLR) ligand-induced IL-17C regulation in primary human airway epithelial cells derived from bronchial and small airway compartments, including normal human bronchial epithelial cells, CF-derived human bronchial epithelial cells, small airway epithelial cells (SAEC), and CF-derived SAEC (D-SAEC-CF). Among the ligands tested, polyinosinic-polycytidylic acid [poly(I:C)], a synthetic TLR3 ligand, consistently revealed differences in IL-17C and IL-8 induction between non-CF and CF-derived cells in both epithelial cell systems. Time-course analyses showed that poly(I:C)-induced IL-17C expression increased gradually and exhibited relatively delayed kinetics compared with the rapid interferon-β response, resembling IL-8 induction. Pharmacological inhibition indicated that c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, and nuclear factor-κB, but not extracellular signal-regulated kinase, were involved in poly(I:C)-induced IL-17C expression. Basal TLR3 and IL-17RE mRNA levels were elevated most clearly in D-SAEC-CF cells; however, IL-17RE knockdown did not significantly reduce poly(I:C)-induced IL-8 production in bronchial epithelial cells. Together, these findings suggest that poly(I:C)-induced IL-17C production may represent a TLR3-dependent epithelial inflammatory response in CF-derived primary airway epithelial cells.

Antibodies are crucial for providing protection against influenza virus infection; however, protective humoral immunity is limited by antigenic drift and shift. Hence, the discovery of broadly neutralizing antibodies (bnAbs) targeting conserved epitopes on hemagglutinin protein evokes the hope of developing a universal influenza vaccine. Because of such historical reasons, much of the effort in universal vaccine design has focused on B cell epitopes. In contrast, despite the critical role of T follicular helper cells in bnAb induction, T cell epitopes have received far less attention. In this review, we summarize the cellular and molecular factors that impact the bnAb development and discuss key limitation factors that restrict their efficient induction.

Coronary artery disease (CAD) has been epidemiologically linked to idiopathic pulmonary fibrosis (IPF); however, the genetic basis of this association remains unclear. Therefore, this study aims to investigate the potential causal relationships between IPF and CAD using a bidirectional two-sample Mendelian randomization (MR) strategy.

Inverse-variance weighted (IVW), MR-Egger, weighted median, and weighted mode approaches were applied to summary statistics obtained from CAD and IPF genome-wide association studies. Heterogeneity among instrumental variables was assessed using Cochran's Q test. Pleiotropy was assessed using MR-Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) analyses. Additionally, the robustness and reliability of the findings were validated by applying a leave-one-out analysis.

The forward MR analysis revealed no evidence supporting a genetic causal association between IPF and CAD (odds ratio [OR] = 0.989, 95% confidence interval [CI]: 0.967-1.010, p = 0.305) after excluding an outlier single-nucleotide polymorphism (SNP) (rs7725218). However, reverse MR analysis demonstrated a significant negative genetic causal association between CAD and IPF (OR = 0.832, 95% CI: 0.711-0.975, p = 0.023). Sensitivity analysis revealed heterogeneity in the forward MR analysis, which was resolved after excluding an outlier SNP, with no evidence of horizontal pleiotropy detected.

This study demonstrates a potential negative genetic influence of CAD on the risk of IPF, providing valuable insights that may guide the development of more enhanced preventive and therapeutic strategies. Future research should further assess the interactions between CAD and IPF to improve disease management and patient outcomes.

ObjectiveSuperselective adrenal arterial embolization with ethanol has demonstrated promising efficacy in patients with primary aldosteronism and lateralized aldosterone secretion. However, approximately 40% of patients have nonlateralized disease, defined as bilateral primary aldosteronism based on adrenal venous sampling.MethodsIn this prospective observational cohort study, 30 patients with primary aldosteronism underwent superselective adrenal arterial embolization, including 16 patients with unilateral primary aldosteronism and 14 patients with bilateral primary aldosteronism confirmed by adrenal venous sampling. Patients were stratified into the unilateral primary aldosteronism and bilateral primary aldosteronism groups. Blood pressure and biochemical parameters were assessed at 15-40 h and at 1, 3, and 6 months after the procedure.ResultsPlasma aldosterone concentration, plasma renin activity, and the aldosterone-to-renin ratio improved significantly in both groups within 15-40 h after superselective adrenal arterial embolization compared with baseline. At 6 months, the rates of complete or partial clinical and biochemical success were 85.7% and 92.9%, respectively, in the bilateral primary aldosteronism group compared with 81.3% and 87.5%, respectively, in the unilateral primary aldosteronism group. Significant reductions in serum sodium levels and microalbuminuria were observed in patients undergoing bilateral superselective adrenal arterial embolization. Body mass index also decreased significantly at 1, 3, and 6 months in both groups. No procedure-related complications were observed during a median follow-up of 6 months.ConclusionsBilateral superselective adrenal arterial embolization may represent a valuable adjunctive treatment strategy for patients with bilateral primary aldosteronism.

ObjectiveHypertension is a common and modifiable cardiovascular risk factor. The triglyceride-total cholesterol-body weight index is a novel metabolic indicator derived from routine clinical measurements, but its association with hypertension remains unclear.MethodsThis longitudinal cohort study used data from 5,731 middle-aged and older adults from the English Longitudinal Study of Ageing, with cross-sectional, prospective, and trajectory analyses. Hypertension was defined as a mean systolic blood pressure ≥140 mmHg, a mean diastolic blood pressure ≥90 mmHg, antihypertensive medication use, or self-reported physician-diagnosed hypertension. For the prospective analysis, participants without hypertension at baseline were followed for a median of 12 years. For the trajectory analysis, repeated triglyceride-total cholesterol-body weight index measurements from previous waves were used to identify long-term triglyceride-total cholesterol-body weight index patterns and assess their associations with hypertension risk. Subgroup analyses and propensity score matching were performed to assess the robustness of the findings.ResultsIn the cross-sectional analyses, each one-unit increase in log-transformed triglyceride-total cholesterol-body weight index was associated with 43% higher odds of hypertension (adjusted odds ratio = 1.43, 95% confidence interval: 1.31-1.55). In the prospective analyses, baseline triglyceride-total cholesterol-body weight index predicted incident hypertension (adjusted hazard ratio = 1.16, 95% confidence interval: 1.05-1.28). Trajectory analyses identified low, moderate, and high triglyceride-total cholesterol-body weight index patterns, showing a graded increase in hypertension risk. Compared with the low-trajectory group, the high-triglyceride-total cholesterol-body weight index group had 69% higher odds of hypertension (adjusted odds ratio = 1.69, 95% confidence interval: 1.37-2.09, p < 0.001).ConclusionTriglyceride-total cholesterol-body weight index was independently and positively associated with the risk of hypertension and may provide a simple measure of metabolic burden relevant to early risk stratification.

This review highlights differences in pathophysiologic mechanisms, diagnostic challenges and therapeutic responses of heart failure with preserved ejection fraction (HFpEF) in women.

Emerging research provides further insight into the pathophysiology of HFpEF in women, and the role of obesity and its impact on treatment. Other theories highlight the role of microvascular dysfunction in women with HFpEF. Gender differences in cardiac imaging parameters for assessment of diastolic dysfunction and elevated filling pressures may require refinement for improved diagnostic accuracy of HFpEF in women. HFpEF is fast becoming the dominant form of heart failure in the US and women have double the lifetime risk of developing HFpEF compared with heart failure with reduced ejection fraction. Gender-specific diagnostic parameters and treatment options have been hindered by low participation of women in cardiovascular trials. Increased participation in larger scale trials and further investigations into sex-specific pathophysiology are needed for improved outcomes in women.

Heart failure in patients with congenital heart disease and particularly single ventricle physiology at all stages of palliation presents significant management challenges. Ventricular assist device (VAD) use in this population is increasing. This review summarizes the recent outcomes, physiologic considerations, and challenges of VAD therapy at each stage of single ventricle palliation.

Survival after VAD implantation has been worse for patients with single ventricle physiology compared with biventricular physiology, though recent data suggest this disparity is narrowing. A variety of continuous and pulsatile flow devices are available for use, though many are not approved by the Food and Drug Administration for use in the pediatric population. Adverse effects are common with VADs at each stage of single ventricle palliation, regardless of device choice. VAD therapy in patients with single ventricle heart disease requires an understanding of the complex cardiac physiology and device mechanics in order to optimize outcomes.

Kidney stones are an increasingly common condition, and evidence suggests a link between stone formation and cardiovascular risk. This study aimed to investigate the association between kidney stones and major adverse cardiovascular events (MACE), including acute myocardial infarction (AMI), heart failure (HF), and stroke. This multicenter retrospective study included 6,660 patients with newly diagnosed stone disease from 2013 to 2017 (KS group) and 19,980 patients without stone disease (NKS group) in the same period. The history of kidney stones was found to be significantly associated with the risk of a major adverse cardiovascular event (aORs: 1.20, 95% CIs: 1.07-1.36, p = 0.003). On multivariable Cox regression analysis, the kidney stone formers had an increased relative risk in stroke (aHRs: 1.21, 95%CIs: 1.02-1.42, p = 0.03) and AMI (aHRs: 1.57, 95%CIs: 1.28-1.92, p < 0.001), but not HF (aHRs: 1.11, 95%CIs: 0.92-1.34, p = 0.3). In contrast, in the female subgroup, kidney stones were associated with an increased risk of HF (aHRs: 1.46, 95% CIs: 1.10-1.93, p = 0.009). The kidney stone formers had an increased risk in stroke and acute myocardial infarction, while only female patients with kidney stones had an increased risk of heart failure.

To compare left atrial (LA) size, emptying function, and strain among non-atrial fibrillation (AF) controls, patients with paroxysmal AF (PAF), and patients with persistent AF (PeAF) using automated 3D Dynamic HeartModel (DHM) and AutoStrain LA, and to examine their association with AF stage.

This retrospective study included 210 participants: 70 non-AF controls, 70 patients with PAF, and 70 patients with PeAF. Controls and patients with PAF were examined during sinus rhythm; acquisition rhythm in PeAF was not uniformly documented. LA volumes and LA ejection fraction (LAEF) were measured using automated 3D DHM, and LA strain was assessed using AutoStrain LA. AF stage was coded as 0, 1, and 2. Multivariable regression analyses evaluated associations with LA volume index (LAVI), LAEF, and LA reservoir strain (LASr). Reproducibility was assessed using intraclass correlation coefficients.

LAVI increased from 29.50 to 38.00 and 58.50 mL/m² across controls, PAF, and PeAF, whereas LAEF decreased from 65.37% ± 7.39% to 50.70% ± 8.28% and 23.34% ± 6.58%, and LASr decreased from 38.00% to 25.05% and 10.20%, respectively (all p < 0.001). After adjustment, AF stage remained associated with higher LAVI (B = 16.43; 95% CI, 13.69-19.17), lower LAEF (B = -19.11; 95% CI, -20.58 to -17.64), and lower LASr (B = -12.37; 95% CI, -13.57 to -11.18; all p < 0.001). Findings were similar after excluding participants with heart rate >100 bpm. Intra-/inter-observer ICCs were 0.989/0.986 for LAVI, 0.975/0.964 for LAEF, and 0.983/0.977 for LASr.

Automated 3D DHM and AutoStrain LA demonstrated graded LA enlargement, reduced emptying function, and impaired reservoir strain across AF temporal patterns. These automated measurements showed favorable reproducibility and may help characterize LA structural and functional remodeling in patients with AF.

Purpose To examine the prognostic value of cardiac MRI-assessed left ventricular (LV) global longitudinal strain (GLS) in patients with moderate to severe chronic aortic regurgitation (AR). Materials and Methods This was a multicenter retrospective study of patients with isolated chronic moderate to severe AR who underwent cardiac MRI between January 2012 and February 2020, within 90 days of the baseline echocardiographic diagnosis. LV volumes, LV ejection fraction (LVEF), and LV GLS were measured with cardiac cine MRI with feature tracking. The end point was all-cause death or heart failure-related hospitalization. Statistical analyses included multivariable Cox proportional hazards regression to assess the association of LV GLS with outcomes, adjusting for age, sex, symptoms, and log EuroSCORE II. Results The study included 175 patients (median age, 58 years [IQR, 44-69 years]; 118 male). Median LVEF and LV GLS were 57% (IQR, 49%-64%) and -14.1% (IQR, -16.1% to -11.4%), respectively. During median follow-up of 3.4 years (IQR, 1.7-5.8 years), aortic valve replacement (AVR) was performed in 64 patients (37%). Composite end point occurred in 23% of patients (n = 41: 11 deaths and 30 heart failure-related hospitalizations). Multivariable analysis revealed that LV GLS ≥ -14% was independently associated with primary outcome in patients receiving medical management (adjusted hazard ratio, 8.70 [95% CI: 2.5, 30]; P < .001), after adjustment for age, sex, symptoms, and log EuroSCORE II. After AVR, patients with LV GLS < -14% had better outcomes (P = .02). In the overall cohort, LV GLS ≥ -14% was independently associated with outcomes (adjusted hazard ratio, 2.47 [95% CI: 1.38-4.43]; P = .002) after adjusting for age, sex, time-dependent AVR, and log EuroSCORE II. Conclusion Cardiac MRI-derived LV GLS was associated with clinical end points in patients with chronic AR. Keywords: Aortic Regurgitation, Aortic Valve, Cardiac MRI, Echocardiography, Left Ventricular Global Longitudinal Strain, MR-Functional Imaging, Cardiac Supplemental material is available for this article. © RSNA, 2026.