Hantavirus pulmonary syndrome (HPS) carries a case fatality rate of 35%-40% and has no approved pharmacologic treatment. Its pathophysiology is rooted in the plasma compartment: cytokines, viral antigens, immune complexes, and platelet-binding glycoproteins circulate as drivers of immunopathologic endothelial injury, noncardiogenic pulmonary edema, and cardiogenic depression. Therapeutic plasma exchange (TPE) achieves bulk clearance of plasma-borne mediators and is established by the American Society for Apheresis (ASFA) for numerous indications that share an analogous mechanistic rationale. This commentary argues that the immunopathology of HPS maps onto the therapeutic targets of TPE, that any intervention would need to be timed to the early cardiopulmonary phase, and that the coagulopathic dimension of the disease provides a mechanistic argument for incorporating plasma into the replacement strategy. We deliberately situate this rationale against the uneven record of TPE in diseases of comparable pathophysiology, in which the intervention has been effective in some settings and without demonstrable benefit in others. The recent Andes virus outbreak aboard the cruise ship MV Hondius, which produced a multinational cluster of severe cardiopulmonary cases, prompted us, as transfusion medicine and apheresis physicians, to articulate this hypothesis. We emphasize that these arguments are mechanistic and hypothesis-generating rather than evidence-based: no clinical data yet support TPE in HPS, and systematic outcome reporting, ideally through a multicenter case series, would be required before any conclusion about efficacy could be drawn.

Pediatric postinfectious bronchiolitis obliterans (PIBO) is a long-term sequela of severe lower respiratory tract infection. However, the underlying pathogenic mechanisms within the airways remain poorly understood.

Bronchoalveolar lavage fluid (BALF) from six children with PIBO and three control children was subjected to transcriptomic, proteomics and untargeted metabolomics analyses. Integrated analysis identified key differentially expressed candidates, among which protein candidates were subsequently validated by ELISAs.

Transcriptomic analysis revealed altered pathways in the BALF of children with PIBO, including pathways related to epithelial differentiation, inflammatory responses, and metabolic processes involving amino acids, purines, lipids, and vitamins. Proteomic analysis further revealed epithelial injury, inflammatory activation, tissue remodeling, and metabolic dysregulation in PIBO patients. Protein-protein interaction (PPI) network analysis identified CXCL8 (interleukin-8, IL-8) as the central hub. Integrative transcriptomic-proteomic correlation analysis further revealed that CXCL8 transcript levels were correlated with the greatest number of differentially expressed proteins (DEPs). Subsequent ELISA validation confirmed elevated CXCL8 protein levels in children with PIBO, which were positively correlated with the predicted FEV1%. Furthermore, 54 proteins, including KRT19, OSM, ADAM8, and PADI2, were significantly correlated with CXCL8 expression. These proteins spanned epithelial, inflammatory, remodeling, and metabolic processes, indicating a clinically relevant network. Untargeted metabolomics analysis revealed alterations in purine, cofactors, and amino acid metabolism, with pyridoxine (vitamin B6) as the most significantly altered metabolite. Integrated multiomic analysis revealed widespread correlations between differentially expressed metabolites and proteins. Notably, putative pyridoxine expression was negatively correlated with the expression of CXCL8 and other key inflammatory proteins, which is consistent with the evidence of disrupted vitamin metabolism observed by transcriptomics. In vitro experiments further showed that pyridoxine treatment reduced CXCL8 secretion in small airway epithelial cells. Together, these findings suggest a potential link between vitamin B6 and inflammatory processes in PIBO.

Multiomic integration revealed molecular signatures characterized by a CXCL8-centric protein network, a potential disruption of vitamin B6 homeostasis, and altered pathways involved in epithelial differentiation, immunity, and metabolism. These signatures converge on core pathogenic mechanisms within the airway microenvironment, including epithelial injury, inflammatory activation, tissue remodeling, and metabolic dysregulation. Collectively, these findings establish an integrative framework for understanding the pathogenesis of PIBO and highlight potential molecular targets for biomarker discovery and therapeutic intervention.

Alpha-1 antitrypsin (AAT) is a serine protease inhibitor that protects tissue from neutrophil elastase and other proteases, particularly in the lung. Mutations in SERPINA1, including the Z mutation, lead to AAT deficiency (AATD), characterized by reduced circulating AAT and increased risk of pulmonary emphysema, liver cirrhosis, and hepatocellular carcinoma. Beyond these well-characterized manifestations, AATD has been associated with panniculitis, rheumatoid arthritis, and glomerulonephritis. Emerging evidence has also suggested a link between AATD and inflammatory bowel diseases (IBDs), although experimental validation is lacking. In this study, we demonstrate that PiZ transgenic mice expressing the polymer-forming ATZ display increased susceptibility to dextran sodium sulfate (DSS)-induced colitis, accompanied by marked Paneth cell abnormalities. The accumulation of polymeric ATZ in Paneth cells is associated with the endoplasmic reticulum (ER) stress response, impaired lysosomal clearance, altered association of Lysozyme-1 (Lyz1) with LC3-containing compartments, and increased Lyz1 secretion. These intestinal alterations were accompanied by changes in microbiota composition, whereas DSS exposure and exogenous lysozyme administration were associated with aggravated intestinal and hepatic pathology. Pharmacological inhibition of ER stress restored crypt homeostasis and normalized Lyz1 secretion. Human Pi*ZZ iPSC-derived intestinal organoids similarly showed ATZ polymer accumulation in secretory epithelial cells and transcriptional alterations involving ER protein processing and epithelial homeostasis. In addition, polymeric ATZ was detected in ileal crypts from a single individual with AATD and intestinal disease. Together, our data reveal a Paneth cell-intrinsic ER stress mechanism linking ATZ accumulation to gut epithelial dysfunction, highlighting a previously underexplored role of the gut-liver axis in AATD.

Centralizing pacemaker implantations delays care for geriatric populations in remote regions, particularly in post-Soviet healthcare systems like Latvia. We hypothesized that a regional hospital could safely establish a high-volume pacing program to overcome geographical barriers, utilizing structured mentorship from a national tertiary center.

This 2-year prospective observational study evaluated 173 consecutive patients (mean age 78.1 years) undergoing permanent pacemaker implantation at Daugavpils Regional Hospital. Procedures were performed by two regional interventional cardiologists transitioning to independent practice, supported by Latvian Cardiology Centre mentors. Endpoints included 30-day major complications, procedural efficiency, surgical learning curve evaluation using Cumulative Sum (CUSUM) analysis, and patient-reported quality of life (AQUAREL, SF-36).

Across 173 procedures (66.5% dual-chamber, 33.5% single-chamber), the overall complication rate was 5.7%. CUSUM analysis demonstrated a complication rate reduction from 8.7% during the initial acquisition phase to a 3.4% expertise plateau. Procedural efficiency stabilized with a mean fluoroscopy time of 3.9 min. Specific complications included lead dislodgement (2.3%), pocket hematoma (1.7%), pneumothorax (1.1%), and wound infection (0.6%), managed successfully without mortality or device abandonment. At 6-month follow-up, patients reported significant quality of life improvements and high trust in the regional team.

Regional high-volume cardiac pacing programs are safe and vital for equitable geriatric care. With structured mentorship, regional hospitals can overcome historical centralization, safely transitioning to independent high-volume centers and achieving an expert-level safety profile non-inferior to tertiary standards.

Supportive care needs may vary substantially among older adults during recovery after ischemic stroke and are relevant to the continuity of post-stroke rehabilitation and follow-up care. A person-centered approach may help characterize heterogeneity in need intensity and inform needs-based supportive care planning. However, evidence on supportive care need profiles and their associated factors in this population remains limited.

A cross-sectional study was conducted among 388 older adults with ischemic stroke recruited from three tertiary hospitals in China. Supportive care needs were assessed using the Stroke Supportive Care Needs Scale. Latent profile analysis was performed using the mean scores of six supportive care need domains. Multinomial logistic regression was used to examine factors cross-sectionally associated with latent profile membership.

Three severity-graded profiles were identified: the low supportive care needs group (Class 1, n = 120, 30.9%), moderate supportive care needs group (Class 2, n = 142, 36.6%), and high supportive care needs group (Class 3, n = 126, 32.5%). Disease-related information needs were prominent across all profiles, whereas life care, symptom management, and rehabilitation care needs were particularly elevated in the high-need profile. Compared with Class 1, older age, anxiety symptoms, and depressive symptoms were associated with higher odds of membership in both Class 2 and Class 3, whereas better self-care ability was associated with lower odds of membership in these higher-need profiles. Higher educational attainment was generally associated with lower odds of higher-need profile membership, while higher income was associated with lower odds of Class 3 membership.

Older ischemic stroke survivors during recovery exhibited severity-graded heterogeneity in supportive care needs. Membership in the higher-need profiles was cross-sectionally associated with older age, poorer self-care ability, anxiety symptoms, depressive symptoms, and lower educational attainment, while higher income was associated with lower odds of membership in the high-need profile. These findings provide descriptive evidence for needs-based assessment and the future development of tiered rehabilitation and follow-up support during stroke recovery. Further longitudinal and external validation is needed to examine the stability and potential application of these profiles in post-stroke care.

Heart failure (HF) is a major public-health burden, and sustained patient education and self-management support are central to long-term care. Digital health technologies provide additional channels for education, monitoring and post-discharge follow-up, but review-level evidence is heterogeneous across intervention models, intensity, feedback mechanisms and outcomes. This study aimed to synthesise review-level evidence on digital health education and digitally supported self-management for adults with HF and to develop practice-oriented evidence statements. We conducted a narrative best-evidence synthesis of review-level evidence, informed by JBI evidence-summary principles and reported according to PRISMA 2020 where applicable. The protocol was registered with the Fudan University Centre for Evidence-Based Nursing (ES20259435). Eight English and Chinese bibliographic databases were searched from inception to 1 December 2025. Eligible evidence included systematic reviews, meta-analyses, network meta-analyses, umbrella reviews, systematic metareviews and scoping reviews indexed in the searched databases. Two reviewers independently screened sources, extracted data and appraised methodological quality using AMSTAR 2 or PRISMA-ScR/JBI-informed criteria. Evidence statements were developed using review quality, directness, consistency, feasibility and likely overlap among primary studies; no recommendation grade was assigned. Of 8,698 records identified, 5,331 were screened after de-duplication, 37 full-text reports were assessed and 27 review-level evidence sources were included. Evidence varied substantially in quality, directness and intervention type. The final synthesis generated 27 practice-oriented statements organised into three tiers: essential core components, conditional implementation components, and emerging or outcome-related statements. Review-level evidence suggests that digitally supported education and self-management may complement routine HF care, particularly when linked to structured clinical feedback, clearly assigned responsibility and escalation pathways. However, the evidence statements should be interpreted conditionally because of methodological limitations, indirectness, intervention heterogeneity and likely overlap among reviews.

To investigate the association between long-term air pollution exposure and incident heart failure in the UK Biobank and further explore potential effect modification by cardiometabolic vulnerability.

We conducted a prospective cohort study among 149,410 UK Biobank participants free of heart failure and ischemic stroke at baseline. Annual mean concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), and particulate matter ≤10 μm (PM10) were assigned using land-use regression models. Incident heart failure and ischemic stroke were ascertained through linkage to hospital and death records. Cox proportional hazards models were used to estimate hazard ratios (HRs) per interquartile range (IQR) increase in pollutants with sequential adjustment for demographic, socioeconomic, lifestyle, and cardiometabolic factors. Effect modification by diabetes, chronic kidney disease, obesity, multimorbidity, and C-reactive protein was assessed using interaction terms.

During a median follow-up of 17.6 years (interquartile range 14.4-20.3), 4,964 incident heart failure events and 3,795 ischemic stroke events occurred. PM2.5 was associated with a higher risk of incident heart failure after full adjustment (HR per IQR 1.045, 95% CI 1.005-1.086; p = 0.027). Participants in the highest quartile of PM2.5 exposure also had a higher risk of heart failure than those in the lowest quartile (HR 1.133, 95% CI 1.037-1.238; P-trend = 0.005). Dose-response analyses suggested an approximately linear relationship between PM2.5 and heart failure risk, with no strong evidence of non-linearity. No statistically significant interaction was observed between PM2.5 and cardiometabolic or inflammatory vulnerability factors (all P for interaction >0.10). In contrast, no significant associations were observed between air pollution metrics and ischemic stroke. Standardized absolute risks of heart failure were low, with a 20-year absolute risk difference of approximately 0.2 per 100 persons between the highest and lowest PM2.5 exposure groups.

In this large population-based cohort, long-term exposure to PM2.5 was associated with a modestly increased risk of incident heart failure. We found no strong evidence that this association differed across major cardiometabolic or inflammatory vulnerability groups. Although the absolute risk difference was small at the individual level, these findings add to the evidence linking long-term PM2.5 exposure to incident heart failure.

Our previous study demonstrated increased skin sympathetic nerve activity (SKNA) in acute coronary syndrome (ACS) patients and its correlation with ventricular arrhythmias. In the current study, we explored specific gut microbial profiles and their relationships with SKNA in ACS patients. Fifteen ACS patients and age- and sex-matched controls were included in this cross-sectional study. Demographic and clinical data were recorded, and SKNA was measured by neuECG. The gut microbial profiles were analyzed by 16S rRNA gene sequencing of the V3-V4 region. Statistically significant differences in alpha diversity (including the Chao 1 index and Faith's phylogenetic diversity) and gut microbial composition were observed between the ACS and control groups. Redundancy analysis and the Mantel test revealed a significant relationship between SKNA and the microbial profiles. The abundance of butyrate-producing bacteria, including Lachnospira and Oscillibacter, was decreased in the ACS group, whereas the abundance of the genus Hungatella, a trimethylamine producer, significantly increased and was positively correlated with the abundance of SKNA. This study is the first to establish an association between SKNA and gut microbial profiles in ACS patients. SKNA may serve as a potential biomarker reflecting the interaction between the nervous system and gut microbiota in ACS.

Cardiovascular diseases (CVDs) remain a leading cause of morbidity and mortality worldwide, underscoring the need for accurate, noninvasive diagnostic methods to support clinical decision-making and treatment planning. Myocardial perfusion imaging (MPI) with positron emission tomography (PET) and single-photon emission computed tomography (SPECT) plays a key role in the evaluation of myocardial ischemia and coronary artery disease. This review provides a comparative overview of PET and SPECT MPI, with particular emphasis on radiopharmaceuticals, technical advances, clinical applications, and the limitations of each modality.

A systematic literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar for studies published between 1990 and July 2026. Search terms included myocardial perfusion imaging, PET radiotracers, SPECT radiotracers, rubidium-82, nitrogen-13 ammonia, technetium-99m sestamibi, flurpiridaz, and relevant combinations of these terms using Boolean operators. Original research articles, clinical trials, and review articles addressing radiopharmaceutical development, image reconstruction techniques, quantitative imaging, and hybrid PET/CT and SPECT/CT technologies were included. Non-English publications, case reports, and studies lacking relevant original or comparative data were excluded. The reference lists of eligible articles were also manually reviewed. Radiotracers were compared with respect to pharmacokinetics, myocardial extraction fraction, target-to-background ratio, image quality, radiation dosimetry, and clinical utility.

SPECT MPI, particularly with ⁹⁹mTc-sestamibi and ⁹⁹mTc-tetrofosmin, remains widely used because of its established clinical infrastructure, relatively low equipment costs, broad availability, and ability to assess both myocardial perfusion and left ventricular function using gated imaging. Its principal limitations include lower spatial resolution, susceptibility to photon attenuation artifacts, and a limited capacity for absolute quantification of myocardial blood flow. PET MPI offers superior spatial and temporal resolution, routine attenuation correction, and quantitative measurement of myocardial blood flow and myocardial flow reserve. Established PET tracers, including ⁸²Rb and ¹³N-ammonia, generally provide higher diagnostic accuracy than conventional SPECT; however, their short physical half-lives require generator-based or on-site cyclotron production and may limit the feasibility of exercise stress protocols. Emerging ¹⁸F-labeled tracers, particularly flurpiridaz, offer several advantages, including a longer half-life suitable for centralized production and distribution, improved image contrast, exercise stress imaging, rapid extracardiac clearance, and a more linear relationship between myocardial tracer uptake and blood flow over a broad flow range. Recent phase III studies have further supported the diagnostic performance of flurpiridaz.

PET and SPECT play important and complementary roles in noninvasive myocardial perfusion imaging. SPECT remains the most widely available and cost-effective technique, whereas PET provides superior image quality, attenuation correction, and quantitative assessment of myocardial blood flow. Ongoing advances in radiopharmaceutical development, hybrid imaging systems, reconstruction methods, and quantitative software are expected to further enhance the diagnostic and prognostic value of MPI and support increasingly personalized approaches to cardiovascular care.

There is an urgent need to better understand the pathophysiology of primary graft dysfunction (PGD) to develop point-of-care methods predicting those at risk. We utilized a multiplex multivariable approach to define cytokines, chemokines, and growth factors in patient-matched biospecimens to identify factors predictive of PGD. Biospecimens were collected from patients undergoing bilateral lung transplantation (LTx) from three sites: donor lung perfusate, post-transplant bronchoalveolar lavage (BAL) fluid (2h), and plasma (2h, 24h, 72h, and 1 and 2 wks). A 71-multiplex panel was performed on each. Cross-validated logistic regression (LR) and random forest (RF) models determined whether analytes from each site, alone or combined with clinical data, discriminated PGD grade 0 (n = 9) vs. 3 (n = 8). BAL fluid at 2h was most predictive of PGD (LR, 0.825; RF, 0.919), followed by multi-timepoint plasma (LR, 0.841; RF, 0.653), then perfusate (LR, 0.565; RF, 0.448). Combined clinical, BAL, and plasma data yielded the strongest performance (LR, 1.000; RF, 1.000). BAL collected 2h post-transplant showed the strongest discriminatory signal for severe PGD in this exploratory cohort. This integrative approach identified IL-1RA, BCA-1, and Fractalkine as hypothesis-generating candidate biomarkers that warrant validation in larger independent studies.