PURPOSE: To evaluate the quantitative performance of Phase-Resolved Functional Lung Magnetic Resonance Imaging (PREFUL-MRI) versus ventilation/perfusion (V/Q) single photon emission computed tomography (SPECT) and compare their correlations with invasive hemodynamics in pulmonary vascular diseases (PVDs). METHODS: This study retrospectively included adult PVD patients who underwent PREFUL-MRI on a 1.5 Tesla MRI and V/Q SPECT within three days from a prospective PVD cohort. Quantitative perfusion parameters including PREFUL-derived perfusion defect percentage (QDP) and SPECT-derived quantitative pulmonary perfusion defect percentage scores (QPPDs) were compared between groups (with and without pulmonary hypertension [PH]), assessed for inter-method agreement, and correlated with hemodynamic parameters from right heart catheterization. RESULTS: A total of 76 adult patients (41 female; median age, 53 years) were included (52 with PH and 24 without PH). Both modalities differentiated PH from non-PH patients significantly (QPPDs: 30.6% vs. 18.2%, p = 0.001; QDP: 38.4% vs. 14.1%, p < 0.001). QDP showed moderate correlation with QPPDs (r = 0.430, p < 0.001) and negligible mean bias (-2.97%). Notably, QDP exhibited stronger correlations with mean pulmonary arterial pressure (r = 0.553) and pulmonary vascular resistance (r = 0.595; both p < 0.01) than QPPDs (r = 0.298 and 0.301, both p < 0.05). CONCLUSION: PREFUL-MRI is a valid, radiation-free functional imaging method for assessing perfusion defects in PVDs. The stronger correlation with hemodynamics indicates that PREFUL-MRI provides enhanced physiological insight and may be more suitable for monitoring disease severity in patients with PVDs.

BACKGROUND: Acute kidney injury (AKI) after heart transplantation (HT) remains incompletely understood. This systematic review and meta-analysis aimed to estimate the pooled incidence of AKI and AKI requiring renal replacement therapy (RRT) after HT, assess associated mortality risks and identify characteristics associated with AKI requiring RRT. METHODS: A systematic literature search identified original studies reporting the incidence of AKI after HT using standardized definitions or reporting AKI requiring RRT. Meta-analyses were conducted using random-effects models. RESULTS: Forty-eight studies covering 14,389 patients were included. The pooled incidence of AKI was 57.05% (95% CI: 49.51-64.28), and AKI requiring RRT occurred in 16.99% (95% CI: 13.58-21.04). Among patients with AKI, 30-day and one-year mortality were of 12.96% (95% CI: 9.80-16.94) and 18.51% (95% CI: 14.56-23.23) respectively. AKI was associated with an approximately threefold increase in 30-day (OR: 2.92; 95% CI: 2.02-4.22) and one-year mortality (OR: 3.07; 95% CI: 1.76-5.34). In patients requiring RRT, 30-day and one-year mortality were 26.47% (95% CI: 18.46-36.41) and 35.13% (95% CI: 28.78-42.06), respectively. AKI requiring RRT was associated with and increased 30-day mortality of more than twelvefold (OR: 12.11; 95% CI: 6.05-24.24) and one-year mortality of more than fivefold (OR: 5.40; 95% CI: 3.88-7.51) Characteristics associated with AKI requiring RRT included higher body mass index, elevated baseline creatinine, chronic kidney disease, perioperative extracorporeal membrane oxygenation support, and longer cardiopulmonary bypass time. CONCLUSIONS: AKI is highly prevalent after HT and is strongly associated with increased early and late mortality, particularly in patients requiring RRT.

Store-operated calcium entry (SOCE) mediated by STIM and Orai proteins is a fundamental Ca influx mechanism that critically regulates intracellular calcium homeostasis and participates in cardiovascular pathophysiology. Upon endoplasmic reticulum Ca store depletion, STIM1/2 activate plasma membrane Orai1/3 channels, initiating Ca entry that drives vasoconstriction, smooth muscle proliferation, platelet activation, and cardiac hypertrophy. Dysregulated SOCE is closely associated with hypertension, atherosclerosis, pulmonary hypertension, and thromboembolic disorders. However, SOCE is not a simple binary pathway but operates within a complex regulatory network. Beyond the core STIM-Orai axis, auxiliary proteins including transient receptor potential canonical 1 (TRPC1), tetraspanin 18 (Tspan18), tropomyosin 3 (TPM3), SOCE-associated regulatory factor (SARAF), and A-kinase anchoring protein 79/150 (AKAP79/150) modulate SOCE amplitude, kinetics, and downstream signaling in a cell- and context-dependent manner. Moreover, the functional consequences of SOCE are highly heterogeneous: Orai1 protects adult cardiomyocytes but promotes pathological hypertrophy in neonatal cells, posing a therapeutic dilemma. Although preclinical studies have shown efficacy of SOCE inhibitors, clinical translation remains hindered by poor isoform selectivity, suboptimal pharmacokinetics, lack of tissue-specific delivery, disease-stage-dependent effects, and absence of validated biomarkers. Importantly, recent evidence has definitively ruled out amlodipine-induced CRAC channel activation at therapeutic concentrations, confirming it as an experimental artifact. This review systematically summarizes the molecular complexity, functional diversity, and translational barriers of STIM/Orai-mediated SOCE, aiming to inform precision therapeutic strategies for cardiovascular diseases.

OBJECTIVES: Understanding whether the novel long-T ITC complex might assist in interpreting clinical prognostic utility compared to established cardiac biomarkers is needed. We determined long term major adverse cardiac events (MACE) and all-cause mortality (ACM) predicated on novel long-T ITC complex and high sensitivity cardiac troponin I (hs-cTnI) and T (hs-cTnT) assays in the emergency department (ED). METHODS: cTn assays were measured on the Mindray CL-1200i platform at presentation in consecutive patients enrolled in 'Mindray hs-cTnI Assay Analytical and Clinical Evaluation for the Diagnosis and RIsk Assessment of Myocardial InfarctIon' (MERITnI) (NCT05853042) trial with suspected ischemia. Sex specific 99th percentiles upper reference limits (URLs) were: hs-cTnI female 14 ng/L, male 15 ng/L; hs-cTnT female 10 ng/L, male 19 ng/L; long-T ITC complex 0.9 ng/L, same for female and male. RESULTS: Of 1,070 patients, 59.4 % were male, 43.4 % White, 45.5 % Black, and 39.5 % ≥65 years. Independent of biomarkers, a continuum of risk over 1 year showed MACE increased to 16.1 % and ACM to 16.5 %. Long-T ITC complex did not show a continuum change, increasing only 0.1 % (HR: 1.001 (1.0-1.001) per ng/L. However, hs-cTnI increased 1.8 % (HR: 1.018 [1.009-1.027] for each ng/L (p<0.0001) and hs-cTnT increased 0.3 % per ng/L (HR: 1.003 [1.001-1.006]) (p=0.0028). Between subjects ≤URLs and >URLs, MACE and ACM all biomarkers showed significant (p<0.0001) differences over 1 year. For MACE in those >URL long-T ITC complex increased 11.2-25.2 %, hs-cTnI 18.0-35.0 % and hs-cTnT 8.9-24.2 %. For ACM in those >URL long-T ITC complex increased 4.5-23.3 %, hs-cTnI 5.0-26.2 %, and hs-cTnT 3.6-24.1 %. CONCLUSIONS: Novel long-T ITC complex did not provide new prognostic value to either hs-cTnI or hs-cTnT. Patients with increased hs-cTnI and hs-cTnT concentrations had marked increases in MACE and ACM risk at 1-year.

Out-of-hospital cardiac arrest remains a major public health challenge worldwide, with survival largely determined by the timeliness, quality, and organization of care. The 2025 Systems saving lives guidelines of the European Resuscitation Council (ERC) emphasize that meaningful improvements in outcomes depend not on isolated interventions but on the coordinated functioning of the entire system of care. This paper, representing the position of the Hungarian Resuscitation Society, summarizes the key elements of the guideline. The recommendations focus on the concepts of the chain of survival and the formula of survival, highlighting the combined importance of scientific evidence, effective education, and local implementation. Increasing community awareness, strengthening advocacy, initiating cardiopulmonary resuscitation education at an early age, and engaging trained lay responders are essential to ensure early intervention. Organizational aspects of emergency care - particularly dispatcher-assisted cardiopulmonary resuscitation, optimization of automated external defibrillator accessibility, and the availability of adequately trained emergency medical teams - further enhance system performance. In-hospital rapid response systems, cardiac arrest centers, and structured follow-up of survivors and their families play a key role in improving long-term outcomes and quality of life. Emerging technologies, including digital tools and artificial intelligence, offer promising opportunities to support early recognition, high-quality resuscitation, and education, although their implementation requires further evaluation and appropriate legal and ethical frameworks. Adopting a comprehensive, system-based approach is essential to improve out-of-hospital cardiac arrest outcomes and to develop sustainable, effective life-saving systems at the national level. Orv Hetil. 2026; 167(30): 1175-1185.

Vascular endothelial growth factor receptor-2 (VEGFR2) is a key target for regulating the endothelial cell lineage and angiogenesis. It is also expressed by lymphatic endothelial cells (LECs) while its participation in lymphangiogenesis remains inadequately characterized. We demonstrate in this study that VEGFR2 is highly expressed in dermal initial lymphatic vessels and valves. The induced deletion of pan-endothelial Vegfr2 at the neonatal stage produced a potent suppression of dermal lymphatic growth, characterized by a thinner lymphatic diameter, a decreased number of LECs and lymphatic valves. Mechanistically, VEGFR2 insufficiency led to a dramatic decrease in lymphatic VEGFR3, a key regulator mediating signals for lymphatic growth and remodeling. RNA sequencing analysis revealed that GO terms enriched for downregulated genes included biological processes related to EC development while pathways related to hematopoiesis and immune responses were upregulated in the skin of Vegfr2 mutants compared with littermate controls. This was further confirmed by RNA-seq analysis of dermal tissues 48 h after endothelial Vegfr2 deletion. Consistently, targeting Vegfr2 in PROX1 cells produced an inhibitory effect on dermal lymphatic growth and recapitulated a similar altered transcriptomic signature. The alteration of lymphatic gene expression was further validated by siRNA-mediated Vegfr2 knockdown in primary LECs, showing a transcriptional trend toward a hematopoietic fate. Findings from this study imply that VEGFR2 is required for the maintenance of endothelial identity, and its insufficiency triggers a transcriptional reprogramming that diminishes VEGFR3-mediated lymphangiogenesis.

BACKGROUND: The presence of an atrial level right to left shunt may be desirable in patients with severe pulmonary hypertension (PH) or failing Fontan circulation. The Occlutech Atrial Flow Regulator (AFR) was originally designed to create an atrial shunt for left heart failure and is currently being used off-label in patients with PH or failing Fontan circulation. There is limited evidence supporting AFR use for these indications. AIMS AND METHODS: We performed a retrospective review of consecutive patients with Fontan circulation or severe irreversible PH who underwent AFR implantation. Comprehensive data were collected and analyzed. RESULTS: Sixteen Fontan and eight PH patients underwent AFR implantation. Median age and weight at implantation were 7.5 years (range 2-34) and 22.3 kg (range 11.3-80), respectively. Twenty-eight devices were implanted in 24 patients during 27 procedures. Successful deployment was achieved in all. The device proved versatile and durable across diverse anatomic substrates, even after multiple repositioning attempts. There were no deaths or urgent surgical interventions. Transseptal puncture or Fontan baffle perforation using a Brockenbrough needle or radiofrequency before AFR implantation was required in 10 patients (42%). The most serious complication was a hemorrhagic stroke related to anticoagulation therapy. Thrombotic events occurred in three Fontan patients (11% of all implantations). CONCLUSIONS: AFR appears to be a promising adjunctive option for PH and failing Fontan patients, with acceptable safety and clinically effective results. Device thrombosis remains a risk, particularly with smaller devices in Fontan circulation, likely related to the Fontan patients' underlying hypercoagulable state.

BACKGROUND: Traditional classifications of atrioventricular nodal reentrant tachycardia (AVNRT) based on cardiac symptomatology, electrocardiographic findings, and reentrant circuits do not capture the full heterogeneity of AVNRT. OBJECTIVE: This study sought to identify distinct phenotypes among patients with AVNRT by using two-step cluster analysis and to determine differential effects of phenotypes on clinical and procedural outcomes. METHODS: All patients (n = 305) underwent catheter ablation and ajmaline challenge testing. A two-step cluster analysis was conducted using 17 demographic/clinical, anthropometric, electrocardiographic, echocardiographic, and anatomic variables. RESULTS: Three distinct clinically and mechanistically relevant clusters were identified. Cluster 1 (Metabolic/Structural Phenotype, n = 44) patients were characterized by older age of onset of AVNRT (53.5 ± 8.5, 43.5 ± 15, and 24.7 ± 10.5 years, p = 4.9 × 10), shorter distance between coronary sinus floor and His bundle potential (22.7 ± 6.1, 24.7 ± 6.8, and 29 ± 7.5 mm, p = 1.3 × 10), higher prevalence of "correlated" (diagnosed ≥ 4 years before AVNRT onset) type 2 diabetes (100%, 0%, and 0%, p = 5.9 × 10) and "correlated" (diagnosed ≥ 6 years before AVNRT onset) structural heart disease (86.4%, 100%, 0%, p = 3.5 × 10) compared to Cluster 2 (Structural Phenotype, n = 78) and Cluster 3 (Anatomic/Genetic Phenotype, n = 183) patients, respectively. Cluster 1 patients had higher prevalence of "pro-arrhythmia" (new-onset and/or symptom worsening/intolerance) with anti-arrhythmic therapy and/or non-cardiac drugs (74.2%, 46.5%, and 31.6%, p = 1.5 × 10), AH prolongation/AV-VA block (20.5%, 7.7%, and 2.2%, p = 8.9 × 10) and aborted ablation (11.4%, 1.3%, and 0%, p = 8.6 × 10) during EP study compared to Clusters 2 and 3 patients, respectively. CONCLUSION: Phenomapping identified three clinically and mechanistically relevant phenotypes of AVNRT associated with clinical and procedural outcomes, underscoring the considerable heterogeneity of AVNRT and the importance of comorbidities and substrates.

OBJECTIVE: To evaluate the impact of anterior versus lateral/posterolateral left ventricular (LV) lead positioning on clinical and echocardiographic outcomes in patients undergoing cardiac resynchronization therapy (CRT). METHODS: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. Electronic databases, including PubMed, Embase, Web of Science, and Cochrane Library, were searched for studies assessing LV lead position and CRT outcomes. Studies comparing anterior with lateral or posterolateral LV lead placement were included. Data were extracted on mortality, CRT response, and left ventricular ejection fraction (LVEF). Pooled effect estimates were calculated using a random-effects model. RESULTS: A total of six studies were included in the qualitative synthesis, with five studies eligible for quantitative meta-analysis. Lateral or posterolateral LV lead positioning was associated with significantly reduced mortality compared to anterior positioning (pooled HR 0.74, 95% CI 0.63-0.86). CRT response rates were significantly higher with lateral/posterolateral positioning (pooled OR 1.40, 95% CI 1.17-1.67). Additionally, patients with optimal lead placement demonstrated greater improvement in LVEF (mean difference 4.0%, 95% CI 1.84-6.16). Heterogeneity across studies was low. CONCLUSION: Lateral or posterolateral LV lead positioning is associated with improved survival, higher CRT response rates, and enhanced reverse remodeling compared to anterior lead placement. Optimizing LV lead position may enhance clinical outcomes in patients undergoing CRT.

Urolithin A (UA) is an important bioactive metabolite generated by the gut microbiota from ellagic acid and ellagitannins. In recent years, it has attracted widespread attention because of its potential value in aging intervention and the prevention and treatment of multisystem diseases. This review systematically summarizes the molecular mechanisms of UA, its effects in disease intervention, and progress in human clinical studies. Existing studies have shown that, with mitochondrial quality control as the core, UA exerts multi-target biological effects through the synergistic regulation of pathways related to inflammatory responses, oxidative stress, mitophagy, and programmed cell death. Findings from in vitro mechanistic studies and animal models suggest that UA may influence pathological processes relevant to degenerative musculoskeletal diseases, cardiovascular diseases, neurological disorders, and cancers, whereas current human clinical evidence remains preliminary and is mainly concentrated in muscle function, exercise-related outcomes, selected metabolic biomarkers, and short- to medium-term safety and tolerability. In addition, this review discusses the bioavailability of UA and its relationship with individual gut microbiota metabolic phenotypes. Future research should focus on high-quality, long-term randomized controlled trials with extended follow-up to promote the application of UA in precision nutrition and its clinical translation.

Congenital esophageal stenosis is a rare and heterogenous malformation often associated with esophageal atresia (EA). Failure of conservative endoscopic treatment leads to surgery. Transthoracic approach is rarely advocated due to the peridiaphragmatic localization of the stricture. Robotic-assisted thoracoscopic surgery (RATS) may offer enhanced precision in confined spaces; its application in patients under 10 kg is still considered a challenge. We report the first description of RATS resection of cartilaginous congenital stenosis and esophagoesophagostomy in a 9.5 kg patient. A female patient with a history of EA type III was corrected via videothoracoscopy, two cardiac surgeries via sternotomy, and laparoscopic treatment of duodenal atresia. During weaning, she did not tolerate thickened food, and endoscopy revealed a patent anastomosis but a distal esophageal stricture. A course of pneumatic dilation was attempted. Persistent clinical and radiological findings indicated the need for surgery. At 15 months, the patient underwent three-trocar thoracoscopy with the da Vinci Xi system. Esophagoscopy helped the identification of the stricture. A longitudinal incision exposed a 2-cm segment of thickened esophageal wall requiring complete excision. A tension-free end-to-end anastomosis was performed using 4/0 PDS. Tracheobronchial remnants were confirmed at histopathologIcal finding. Esophageal contrastography demonstrated a good diameter anastomosis. One month after the operation, she was able to swallow solid food. Surgery for congenital stenosis is indicated when endoscopic management fails. RATS for esophageal diseases in patients under 10 kg is feasible, and peridiahragmatic esophagus particularly suits to this technique. Previous accesses to the thorax seems not to be a limitation.

Eculizumab is a highly effective and generally safe therapy for atypical hemolytic uremic syndrome (aHUS), a rare subtype of thrombotic microangiopathy (TMA). This report presents a case of recurrent episodes of acute decompensated heart failure temporally related to its administration, a possible adverse effect that is exceedingly rare and poorly documented in the literature. A 45-year-old woman presented with altered mental status and received a clinical diagnosis of complement-mediated thrombotic microangiopathy based on the presence of thrombotic microangiopathy and marked complement activation. Within hours of the first and subsequent eculizumab infusions, she developed recurrent episodes of acute decompensated heart failure, evidenced by respiratory distress, tachycardia, soaring pro-BNP levels, and echocardiographic confirmation of left ventricular dysfunction. These episodes consistently impeded weaning from mechanical ventilation. The temporal association was reinforced when withholding eculizumab was associated with symptom resolution, while a subsequent reduced-dose challenge promptly reinduced cardiac decompensation. This case raises the possibility that eculizumab may trigger acute decompensated heart failure in susceptible patients. It alerts clinicians to monitor for this potentially life-threatening complication and underscores a significant therapeutic dilemma when first-line therapy is associated with severe adverse effects. Further investigation is needed to understand the mechanism and identify at-risk patients.

BACKGROUND: Acute decompensated heart failure (ADHF) is a major cause of morbidity and mortality, with congestion being the primary reason for hospitalization. Despite treatment, many patients are discharged with residual congestion, hence the growing interest in utilizing biomarkers as objective tools to guide decongestion therapy. Carbohydrate Antigen 125 (CA125) has emerged as a promising biomarker of systemic congestion, with potential advantages over routine markers. This study evaluated the relationship between CA125 changes and clinical congestion score (CCS) at discharge and assessed its association with 30-day outcomes. METHODS: This was a prospective cohort study conducted over seven months at Moi Teaching and Referral Hospital, a tertiary hospital in Western Kenya. Patients with ADHF were enrolled. CA125 levels were measured at admission and discharge using an automated immunoassay. In addition, other markers of congestion, i.e., CCS, NT-proBNP levels, body weight, and inferior vena cava (IVC) diameter, were assessed at both admission and discharge. The 30-day outcomes, which included all-cause mortality and heart failure (HF) rehospitalizations, were recorded. Statistical analyses included correlation and generalized linear models. RESULTS: A total of 213 patients were included, with an in-hospital mortality rate of 23.5%. There was a significant correlation between changes in CA125 levels and improvements in CCS at discharge ( = 0.018). Patients with in-hospital CA125 reductions had lower rates of the composite 30-day outcome (all-cause mortality or HF rehospitalization) at 15%, compared to 40% in those with rising CA125 levels. CONCLUSION: A reduction in CA125 levels during hospitalization is associated with better clinical decongestion and improved short-term outcomes.

Ischemic stroke (IS) is a complex cerebrovascular disease with multifactorial etiology and pathological mechanisms, characterized by high morbidity, disability, and mortality rates. Although mechanical thrombectomy, intravenous thrombolysis, and neuroprotective interventions have improved acute management, effective brain-targeted delivery remains limited by the blood-brain barrier, short therapeutic windows, heterogeneous ischemic lesions, and secondary injury after reperfusion. Biomimetic nanomedicines have emerged as promising platforms for IS therapy because they can inherit biological functions from cell membranes, extracellular vesicles, or endogenous ligands, thereby improving biocompatibility, immune evasion, circulation stability, and lesion targeting. However, their clinical translation is still constrained by biosafety and immunogenicity concerns, uncertain pharmacokinetics and reproducible large-scale manufacturing, quality control, and regulatory requirements. Moreover, the balance between drug-loading capacity and target release efficiency remains a key challenge. Excessive cargo loading may compromise nanocarrier stability, whereas insufficient loading may fail to achieve therapeutic efficacy. Therefore, rational nanocarrier design for IS should coordinate brain accumulation, stable systemic circulation, lesion-selective activation, efficient loading, and controllable release. In this review, we discuss how stimuli-responsive biomimetic nanomedicines exploit pathological cues such as reactive oxygen species, acidosis, enzymes, inflammatory mediators, or external stimuli for spatiotemporally controlled therapy and combined therapy. This review critically summarizes IS pathophysiology, major biomimetic nanocarrier types, and the design principles and response mechanisms of stimuli-responsive biomimetic systems. Finally, current limitations and future directions are discussed, with emphasis on biosafety evaluation, standardized characterization, scalable manufacturing, clinically relevant models, and rational integration of precision-responsive designs to accelerate translation.

OBJECTIVE: Sepsis elicits neuroinflammation in the medullary visceral zone (MVZ), which disrupts the cholinergic anti-inflammatory pathway (CAP). However, the underlying mechanisms and translational therapeutic potential remain poorly defined. METHODS: Adult male Sprague-Dawley rats received either intracerebroventricular lipopolysaccharide (LPS; 25 μg/25 μL) to induce MVZ neuroinflammation model rats, or intraperitoneal LPS (6 mg/kg) to establish polymicrobial sepsis model rats. Anti-inflammation groups were involved with minocycline sucrose solution (120 mg/L) which was administered by drinking for 4 days prior to LPS challenge. CAP transection groups were undergone right cervical vagotomy 7 days before anti-inflammation interventions. Murine sepsis score (MSS), mortality rates, heart rate variability (HRV), cytokine levels in blood and medulla, systemic immunity level, and the expression levels of glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (IBA-1), CD22, tumor necrosis factor-α (TNF-α), Munc13-1, Synaptophysin (SYN), and postsynaptic density protein 95 (PSD-95) in the MVZ were measured and analyzed. RESULTS: Both sepsis and MVZ neuroinflammation model rats showed significantly increased mortality and MSS scores, depressed HRV parameters, and upregulated expressions of GFAP, IBA-1, CD22, and TNF-α, with downregulated expressions of Munc13-1, SYN, and PSD-95 in the MVZ. Synaptic structural damage including reduced synaptic vesicles, decreased RT1.D expression on lymphocytes, increased percentages of Th17 and Treg lymphocytes, and increased serum levels of TNF-α, IL-10, and INF-γ were observed. Anti-inflammatory intervention reversed these changes in both model rats, whereas CAP transection partially abolished the anti-inflammatory benefits, confirming CAP dependence. CONCLUSIONS: Sepsis-induced MVZ neuroinflammation dismantles synaptic integrity and CAP modulation, which intensifies peripheral cytokine storm. Early central anti-inflammation repairs MVZ synaptic plasticity and reinstates vagal immunomodulation, which may provide a translational strategy to limit septic escalation.

INTRODUCTION: Heated tobacco products are often marketed and perceived as less harmful than regular cigarettes, although their acute cardiovascular toxicity is unknown. In this study, the acute effect of exclusive IQOS use on several cardiovascular parameters was assessed, and compared with those of both exclusive cigarette smokers and never smokers of tobacco products. The puffing behavior of both groups of tobacco users was also characterized. METHODS: An independent quasi-experimental study was conducted in Milan, Italy, in March-June 2024. Three groups of participants - frequency matched by age and gender - were recruited: exclusive conventional cigarette smokers (n=25, CS), exclusive IQOS users (n=26, IU), and never smokers (n=27, NS). All participants were aged ≥18 years, had a body mass index between 18.5 and 25 kg/m2, did not have respiratory or cardiovascular diseases, nor were they taking medications associated with these. The acute cardiovascular impact associated with the use of a regular cigarette or IQOS was measured by comparing systolic and diastolic blood pressure, and heart rate prior to (T0) and upon (T1) product consumption. Video-assisted measurement of the total length of the smoking session, number of puffs, puff duration, and inter-puff interval was carried out. RESULTS: The mean heart beats per minute of conventional cigarette (87.4 at T1 vs 74.6 at T0) and IQOS users (86.7 at T1 vs 75.5 at T0) upon product use were higher compared with their baseline measurement (p<0.001) and with the control group (70.5 at T1 vs 74.1 at T0; p<0.001). The increases (T1-T0) in the three cardiovascular measures observed for IQOS users were not different with those of conventional cigarette smokers and significantly higher than the changes of never smokers (Δ systolic blood pressure: -5.9 in NS, 2.4 in CS and 0.3 in IU; Δ diastolic blood pressure: -1.3 for NS, 4.6 for CS and 3.1 for IU; Δ heart rate: -3.7 for NS, 12.8 for CS and 11.1 for IU). IQOS users exhibited shorter smoking sessions than cigarette smokers (4 vs 3.5 minutes, p<0.05), in which they took more frequent (16.2 s for CS, 11.8 s for IU, p<0.001) and longer puffs (1.7 s for CS, 2.3 s for IU, p<0.001). CONCLUSIONS: This study shows analogous acute physiological changes of conventional and heated tobacco products on the human heart. The reported differences in puffing behaviors between cigarette and IQOS users show, to our knowledge, for the first time, the importance of using real-life puffing behavior data in laboratory settings.

BACKGROUND: A great number of individuals with type 2 diabetes mellitus (T2DM) suffer from cardiovascular diseases (CVD). Dietary patterns play a key role in preventing and controlling the complications of T2DM and CVD. The aim of this study is to investigate the association between dietary patterns derived from reduced rank regression (RRR) and novel atherogenic indices in patients with T2DM. METHODS: In this cross-sectional study, 226 patients with T2DM aged 30-75y were participated. The Risk of CVD was assessed using the novel atherogenic indices such as the Cardiometabolic Index (CMI), Atherogenic Index of Plasma (AIP), Lipid Accumulation Plasma (LAP), and Atherogenic Coefficient (AC). Dietary intakes were collected through a validated food frequency questionnaire. Binary logistic regression was employed to examine the relation between dietary patterns and study outcomes. RESULTS: The mean age of participants was 62.81 ± 7.19 years. After adjusting all confounders, participants with the highest adherence to healthy dietary pattern had significantly lower odds for CMI (OR = 0.22; 95% CI: 0.08, 0.61), AIP (OR = 0.15; 95% CI: 0.05, 0.40), AC (OR = 0.03; 95% CI: 0.002, 0.56), compared to those with the lowest adherence. However, LAP did not change significantly across tertiles of the healthy dietary pattern in the fully adjusted model (OR = 0.49; 95% CI: 0.15, 1.57). CONCLUSIONS: This cross-sectional study suggests that higher adherence to healthy dietary pattern was associated with lower odds of elevated CMI, AIP, and AC indices, but not LAP, among patients with T2DM. Due to the cross-sectional design of the study, causality cannot be inferred, therefore prospective studies are recommended to replicate these findings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-026-02024-0.

AIMS: To investigate the feasibility and preliminary efficacy of a 12-week remotely-delivered exercise snacks (ES) intervention in adults with type 2 diabetes. MATERIAL AND METHODS: Insufficiently active adults with type 2 diabetes (N = 69; 46 females; mean age ± SD: 58 ± 11 years) were randomised to an ES or mobility/stretching comparator group (CON), which involved 4 × 1-min bouts of either vigorous or low intensity exercise, respectively, on ≥ 5 days/week. The primary outcome was feasibility based on adherence. Secondary outcomes included exercise enjoyment (1-7 scale), rating of perceived exertion (RPE; 0-10 scale), heart rate (HR), haemoglobin A (HbA), blood biomarkers of cardiometabolic health, 30-s sit-to-stand capacity, grip strength, estimated maximal oxygen uptake, and anthropometrics. RESULTS: Weekly adherence (estimated marginal mean [95% confidence interval]: 18 bouts [16-21] for both groups; p = 0.99) and total enjoyment (ES: 4.5 [4.1-4.8] vs. CON: 4.3 [4.0-4.7]; p = 0.64) were high and not different between groups. Despite higher RPE (5.7 [5.4-6.1]) and peak HR (73 [70-77] % of age-predicted HR maximum) in ES versus CON (2.0 [1.7-2.4] and 61 [58-64] % of age-predicted HR maximum, respectively) (all p < 0.001), there were no between-group differences in the change in any secondary outcome (all p > 0.05) except for greater sit-to-stand capacity in ES after training (between-group effect estimate [95% confidence interval]: 1.9 repetitions [0.3-3.4]; p = 0.02). CONCLUSIONS: Exercise snacks were feasible to perform in the real world and improved sit-to-stand capacity to a greater extent than CON in adults living with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06407245.

In a Nutshell, platelets are small and anucleate, yet remarkably versatile cells that bridge the gap between haemostasis, thrombosis, inflammation and adaptive immunity. This expanded functional spectrum uncovers new opportunities for understanding and treating immune-mediated thrombocytopenia and other haematological diseases.

The 2026 AHA/ACC guideline on acute pulmonary embolism introduces normotensive shock as a clinically relevant pre-cardiopulmonary failure state with implications for treatment escalation. Evidence from cardiogenic shock indicates that tissue hypoperfusion despite preserved arterial blood pressure is associated with substantial mortality, underscoring the need for early recognition. This requires reliable, rapidly obtainable, and broadly applicable criteria. As several proposed indicators are limited by delayed availability or restricted bedside use, shock assessment should integrate concordant clinical signs of tissue hypoperfusion rather than rely on a single marker. Prolonged capillary refill time and skin mottling may complement lactate as bedside markers of abnormal skin perfusion. Critical care echocardiography further supports this multimodal approach by confirming acute right ventricular pressure overload, excluding alternative causes of circulatory failure, and assessing right ventricular adaptation and right ventricular-pulmonary arterial coupling. Early recognition may identify patients at imminent risk of deterioration who could benefit from timely treatment escalation, including consideration of reperfusion therapy.

OBJECTIVES: This study aimed to investigate the interaction between a genetic risk score for coronary artery disease (CAD) and measures of physical activity on coronary artery calcification (CAC) in a population-based cohort. Specifically, it sought to determine whether physical exercise, known to be protective against high CAC, influences the expression of genetic risk factors for CAD. METHODS: Data were obtained from the Heinz Nixdorf Recall study, including 3938 participants aged 45-74 years with European ancestry. CAC was measured using electron beam computed tomography. The genetic risk score (GRS) was calculated using 158 CAD-related genetic loci. Physical activity during the last four weeks was assessed through standardized interviews, resulting in measures of (1) engagement in physical exercise and (2) the total metabolic equivalents of general physical activity per week (METh/week). Linear regression models were used to analyze the associations of physical activity and genetic risk with log-transformed CAC, adjusting for confounders age, sex, and education. RESULTS: Participants not engaging in physical exercise had a 1.336-fold (95%-CI: 1.171 to 1.533) higher CAC compared to those who exercised. No association was found between METh/week and CAC. The GRS was associated with a 1.206-fold (95%-CI: 1.130 to 1.287) higher CAC per standard deviation. Interaction analyses indicated that the genetic effect on CAC was slightly stronger in participants with higher METh/week levels, showing a 1.306-fold (95%-CI: 1.145 to 1.490) higher CAC per standard deviation of the GRS in the highest METh/week quartile compared to 1.109-fold (95%-CI: 0.978 to 1.259) higher CAC in the lowest quartile. No interaction was observed for engagement in physical exercise. CONCLUSIONS: While physical activity in sum was associated with lower levels of CAC, individuals reporting higher physical activity levels may also be less exposed to other non-genetic risk factors for CAD, leading to a slightly stronger association of genetic factors with CAC.

INTRODUCTION: Human Immunodeficiency Virus (HIV) infection has currently become a manageable chronic disease with the prevalence of antiretroviral therapy (ART). The increase in life expectancy and the rising number of people aged more than 50 years among people living with HIV (PLWH) both indicate an increasing risk of chronic non-communicable diseases, especially cardiovascular disease (CVD). Moreover, the contribution of traditional risk factors to CVD far outweighs that of HIV-related factors, which indicates that interventions for reducing CVD risk factors in PLWH are urgent. METHODS: We designed a multicentre non-randomized controlled trial (nRCT), which incorporated six acquired immunodeficiency syndrome (AIDS)-designated hospitals in Zhejiang Province, and three rounds of surveys were conducted from January 2023 to January 2024. Assessments were performed at baseline, 3 months and 6 months post-intervention, respectively. For the intervention group, PLWH were informed of their 5/10-year CVD risk, on the basis of the assessment in baseline, verbally or online to warn them of the risk of having CVD; at the same time, personalized risky behaviour reinforcement intervention was implemented face-to-face or online for about 15 min. For the control group, PLWH were not informed of the 5/10-year CVD risk and only received routine health education in the clinic without additional intervention. Intervention effects were assessed using 5/10-year CVD risk, health-related behaviours (e.g., smoking, alcohol consumption, physical activities and dietary nutrition), as well as CVD cognitive level. To minimize baseline differences and reduce confounding due to non-treatment factors (e.g., socio-demographic characteristics), propensity score matching (PSM) was applied to construct comparable intervention and control groups, and a generalized estimating equation (GEE) was used to estimate the effect of the intervention. This trial was retrospectively registered with the Chinese Clinical Trial Registry (ChiCTR2500112178) on 11 November 2025. RESULTS: A total of 948 PLWH were incorporated at baseline, after excluding ineligible participants, including 494 in the intervention group and 454 in the control group. The average age was 42.08 ( ± 11.94) years, with 826 male patients (87.13%). A total of 362 pairs were successfully matched after PSM. After matching, no statistical differences remained between the two groups. After 6 months' intervention, the intervention group showed significant improvements in CVD cognitive level, with a total increase of 2.30 points compared with 0.41 points in the control group (P = 0.028). Additionally, PLWH who almost never drink and have > 8 h of sedentary time per day, increased and decreased 4.54% and 1.46% respectively, compared with the control group (P < 0.05). The 10-year CVD risk decreased by 0.63% in the intervention group and 0.18% in the control group. Moreover, the smoking rate and drinking rate decreased more in the intervention group compared with the control group, and the physical exercise compliance rate increased more as well, though there was no statistical difference compared with the control group (P > 0.05). CONCLUSIONS: Risk warning and behavioural intervention effectively improved CVD cognitive level. Although the risk warning and behavioural intervention could not make PLWH completely quit smoking or using alcohol, the intervention led to notable improvements in reducing the frequency of some health risk behaviours.

AIMS/HYPOTHESIS: Environmental exposures have been adversely associated with the risk of diabetes but their role in the remission and progression of prediabetes (impaired glucose tolerance [IGT] and/or impaired fasting glucose [IFG]), especially different phenotypes, is poorly understood. This study aimed to investigate the relationship between environmental exposures and remission or progression of prediabetes phenotypes. METHODS: Data were derived from the KORA (Cooperative Health Research in the Region of Augsburg) cohort in Southern Germany (2006-2022). Glucose tolerance status was defined according to the 1999/2006 WHO criteria. We included annual values of particulate matter (PM), light at night (LAN), normalised difference vegetation index (NDVI), imperviousness (IMP) and air temperature variation (T). We fitted complementary log-log regression models for associations between IQR changes in exposures and the incidence of prediabetes phenotypes (isolated impaired fasting glucose [iIFG], isolated impaired glucose tolerance [iIGT], or their combination [IFG+IGT]), remission to normal glucose tolerance (NGT) or progression to type 2 diabetes. We also applied Quantile g-computation regression models for joint association analysis. RESULTS: During the follow-up, 370/1618 participants developed prediabetes (124 iIFG, 199 iIGT and 47 IFG+IGT). Among participants with prediabetes, 136/367 (without medication) regressed to NGT and 133/420 progressed to type 2 diabetes. We observed consistent associations of air pollutants and the built environment with iIGT or IFG+IGT. For example, an IQR increase in PM (aerodynamic diameter ≤2.5 μm) showed an HR of 1.89 (95% CI 1.07, 3.31) for the risk of IFG+IGT and 1.59 (95% CI 1.03, 2.46) with a decrease in NDVI. Co-exposure to environmental mixtures (higher air pollution, T, IMP and LAN, and lower NDVI) was associated with increased risks of iIFG, iIGT and IFG+IGT. Additionally, lower NDVI (HR 0.52 [95% CI 0.28, 0.96]), higher LAN (HR 0.22 [95% CI 0.08, 0.62]) and higher IMP were associated with reduced remission of iIFG but we found no statistically significant associations with the progression to type 2 diabetes. CONCLUSIONS/INTERPRETATION: The findings indicate potential heterogeneity in environmental exposures and prediabetes phenotypes. Specifically, they are associated with increased incidence of IGT and decreased remission of iIFG.