BackgroundPulmonary embolism (PE) may be asymptomatic due to the compensatory function of the lungs themselves, which easily leads to missed diagnosis and increased risks. Although computed tomography pulmonary angiography (CTPA) can improve the detection rate, routine CTPA screening for patients with concurrent lower extremity deep vein thrombosis (DVT) still faces challenges. These include limited medical resources, restricted use of contrast agents (e.g., allergies, renal function issues), and low specificity of D-dimer. Therefore, there is a need to develop optimized diagnostic strategies based on inpatient DVT populations to accurately identify high-risk patients requiring CTPA, while acknowledging that these findings cannot be directly generalized to all DVT outpatients and reduce unnecessary contrast agent exposure.MethodsThis retrospective study analyzed patients admitted with lower extremity DVT (Jan 2022-Apr 2024). After excluding those with acute PE symptoms or other key confounders (e.g., recent anticoagulation), 401 patients were included. All underwent CTPA and were classified into asymptomatic PE (n=198) or isolated DVT (n=203) groups. Predictors of asymptomatic PE were identified using binary logistic regression.ResultsAfter screening based on inclusion and exclusion criteria, 401 patients were finally included in the analysis, with 198 cases in the asymptomatic PE group and 203 cases in the DVT group. Multivariate regression analysis showed that hypertension, neutrophil-to-lymphocyte ratio (NLR), smoking duration, right distal DVT, right proximal DVT, and lower extremity swelling and pain were independent risk factors for asymptomatic PE (OR = 3.461, 1.303, 1.103, 2.878, 4.495, 7.176,). The area under the curve (AUC) of the model was 0.874, with a sensitivity of 73.74% and a specificity of 82.27%.ConclusionThe combined detection of these independent risk factors-hypertension, NLR, smoking duration, right distal DVT, right proximal DVT, and lower extremity swelling and pain-is expected to facilitate early screening for asymptomatic PE in hospitalized DVT populations, with further external verification required to extend its applicability to broader DVT cohorts.

ObjectivesLong-term symptoms following infection with acute respiratory syndrome coronavirus-2 (SARS-CoV-2), termed post-acute sequelae of SARS-CoV-2 infection (PASC) or Long COVID (LC), persist beyond 90 days and may impact at least 10% of patients with acute infection. The exact cause of LC remains unknown, but several theories include persistent viral particles, immune dysfunction, and autonomic nervous system (ANS) imbalance, particularly involving the vagus nerve. Given the role of the vagus nerve in inflammation regulation, vagal nerve stimulation (VNS) is being explored as a treatment option. The present study aimed to evaluate the feasibility, safety, and exploratory effects of a handheld external transcutaneous cervical non-invasive VNS (tcVNS) on the primary endpoint of Post-COVID Functional Status (PCFS) grade, alongside secondary outcomes such as LC-related fatigue and other symptoms.MethodsParticipants from our Post COVID Care Clinic were randomized into treatment (tcVNS treatments two minutes, three times a day) and control (no VNS) groups for a study period of 12 weeks. Participants completed validated questionnaires, PET-CT scans, and inflammatory cytokines at baseline and 12 weeks.ResultsAll randomized patients (8 tcVNS, 10 control) completed the 12-week study. Participants randomized to tcVNS were observed to have improvements in PHQ-9, PROMIS-F, and COMPASS-31 when compared to controls, but these differences were not statistically significant. Cortisol and DHEA were also observed to increase less in the tcVNS group when compared to the control group, but these changes were also not statistically significant.ConclusionstcVNS was well tolerated and may be a promising therapeutic approach for LC, a chronic disease with no approved treatments and very low rates of complete recovery.

JAK inhibitors (JAKi) represent a novel therapeutic approach for treating the immune-mediated dermatologic diseases alopecia areata (AA) and atopic dermatitis (AD). JAKi have shown a favorable safety profile in controlled clinical trials; however, real-world safety data in routine dermatologic practice remain limited. The objective of this study is to evaluate the safety of JAKis (abrocitinib, baricitinib, upadacitinib, and ritlecitinib) in patients with AA or AD in a real-world setting.

We conducted a single-center retrospective observational study based on electronic medical record data from December 2020 to June 2025. Adult patients with a confirmed diagnosis of atopic dermatitis or alopecia areata who were treated as per routine clinical practice with a dermatologic JAKi were included. Adverse events (AE) were retrospectively collected.

A total of 376 adult patients were included. AE events were observed across all agents and were predominantly mild to moderate. Mild total cholesterol increase, weight gain, and upper respiratory tract infection were the most common AE. Discontinuation was mainly driven by loss of efficacy, while AE-related discontinuations were less frequent and heterogeneous in nature. Importantly, only one case of venous thrombo-embolism was reported in a patient with other thrombotic risk factors, and no cases of major adverse cardiovascular events (MACEs) were recorded. Four cases of malignancies were reported. Notably, sex-specific differences emerged in metabolic adverse events, with weight gain occurring more frequently among female patients. Menstrual alteration, although rare, was a newly described safety event and was the leading cause of treatment discontinuation due to safety issues.

While no safety signals regarding MACEs or cancer emerged, other metabolic events, such as cholesterol increase, weight gain and menstrual alterations, were identified. These findings highlight that routine clinical practice represents a less controlled and more heterogeneous setting than randomized trials, underscoring the importance of continuous real-world safety monitoring to fully characterize treatment-associated risks.

A case of chronic proliferative rhinitis (CPR) associated with Salmonella enterica subsp. diarizonae serovar 61:(k):1,5,(7) (SED) is described in a 3-year-old ewe from the university teaching farm in Transylvania, Romania. Clinical examination revealed bilateral seromucous nasal discharge and visible proliferative masses within both nasal cavities. Infrared thermography demonstrated increased heat emission over the nasal region, consistent with active inflammation. Computed tomography imaging showed marked proliferative invasion within the ventral nasal turbinates. Histopathology and immunohistochemistry confirmed chronic proliferative rhinitis characterized by fibrovascular tissue proliferation, epithelial cell hyperplasia, and mixed inflammatory cell infiltrate, predominated by lymphocytes, plasma cells and macrophages. SED was isolated as the sole microorganism from nasal swabs and confirmed by serotyping, PCR, and immunohistochemistry. To the authors' knowledge, this is the first documented case of CPR associated with SED in Romania and in Southeastern Europe, highlighting the need to include CPR among the differential diagnoses for adult sheep with chronic upper respiratory disease, and to include SED within its aetiological agents.

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.

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_CAD) 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.

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_CAD 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_CAD 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.

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.

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.

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_sd). 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.

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_2.5 (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_sd, 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.

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.

Neurodevelopmental disorders are a major non-cardiac source of morbidity in congenital heart disease (CHD), but families' experiences of risk communication and developmental care remain insufficiently described. We aimed to characterize parental perspectives on neurodevelopmental risk communication, referral, care coordination, and unmet needs in France. We conducted a nationwide, anonymous, cross-sectional online survey of parents of children with CHD in France between May and June 2025. The questionnaire, co-developed with expert parents and a national patient organization, assessed timing and modalities of risk communication, access to follow-up pathways, coordination, and family impact. Of 667 invited families, 293 completed the survey (response rate 43.9%). Among 293 respondents, 184 (62.8%) reported a prenatal CHD diagnosis and 189 (64.5%) reported critical CHD. Overall, 165 parents (56.3%) felt they had not been informed about neurodevelopmental risk. Of 127 parents informed by health professionals, 83% received no written materials or practical guidance and 45% reported no referral to professionals or support services. Almost all respondents (290/293, 99.0%) wanted information about neurodevelopmental risk. Among children older than 3 years, parents reported neurodevelopmental delay or disorder in 120 of 210 cases (57.1%), yet only 11 of these children (9.2%) were enrolled in a multidisciplinary perinatal healthcare network. Three quarters of parents reported no identified coordinator for developmental care.

 Parents described substantial gaps in neurodevelopmental risk communication, care coordination, and continuity of follow-up for children with CHD. Structured, family-centered pathways should begin at diagnosis and extend into school age.

• Children with congenital heart disease are at increased neurodevelopmental risk, and expert guidance recommends surveillance, referral, and coordinated follow-up.

• This nationwide parent survey identifies major gaps in risk communication, referral, and coordination, supporting staged counselling and longitudinal developmental pathways into school age.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and sacubitril/valsartan (SAC/VAL), an angiotensin receptor-neprilysin inhibitor, are both US Food and Drug Administration-approved and guideline-recommended therapies for heart failure with reduced ejection fraction (HFrEF). While each has demonstrated significant reductions in cardiovascular morbidity and mortality, direct comparative evidence remains limited, particularly in relation to patients' diabetes status.

To compare the effectiveness of SAC/VAL versus SGLT2i in preventing HF-related and all-cause hospitalizations among patients with HFrEF, with or without diabetes, using real-world data from the MarketScan^® Research databases.

This new-user, active-comparator cohort study using MarketScan^® Commercial and Medicare databases (2019-2023) identified patients with HFrEF by using International Classification of Diseases codes. Patients who initiated SAC/VAL or SGLT2i treatment were included, with the index date defined as the first prescription fill. Continuous health plan enrollment ≥ 6 months prior to HFrEF diagnosis through the index date was required. To balance baseline characteristics between groups, we applied stabilized inverse probability of treatment weighting (IPTW). Cox proportional hazards models compared risks of HF-related and all-cause hospitalizations in cohort analyses defined by diabetes status, diagnosis, and antidiabetic medications.

After IPTW, the study included 7406 patients initiating SAC/VAL and 5101 patients initiating SGLT2i. Among patients with diabetes, there were no significant differences in the risks of HF-related hospitalization (adjusted hazard ratio [aHR] 1.13, 95% confidence interval [CI] 0.98-1.30) or all-cause hospitalization (aHR 0.99, 95% CI 0.90-1.09) between medication groups. In contrast, among patients without diabetes, initiation of SAC/VAL was associated with significantly lower risks of HF-related hospitalization (aHR 0.65, 95% CI 0.56-0.76) and all-cause hospitalization (aHR 0.69, 95% CI 0.62-0.77).

In a real-world cohort of patients with HFrEF and without diabetes, but not those with diabetes, SAC/VAL initiation was associated with reduced risks of HF-related and all-cause hospitalizations compared with SGLT2i initiation. These findings provide supportive evidence that may inform clinicians when selecting therapy for patients with HFrEF.

This article reviews the existing literature on non-LDL biomarkers in atherosclerotic cardiovascular disease (ACSVD), atherogenesis, and ischemic stroke risk, including a discussion of potential future applications for secondary prevention of stroke.

Although foundational studies established the strong link between elevated low-density lipoprotein-cholesterol (LDL-C) with the development of atherosclerosis and increased cardiovascular risk, a growing number of recent studies have shown that more precise cerebrovascular disease (CVD) risk stratification can be achieved by using other components of the traditional lipid panel along with additional lipoprotein assays. The specific relationship between these non-traditional markers of atherosclerosis and ischemic stroke risk remains incompletely defined. Lipid measures beyond LDL-C including updated interpretations of the standard lipid panel, such as the triglyceride-to-high density lipoprotein ratio (TG:HDL) as well as testing for lipoprotein (a) (Lp(a)) and apolipoprotein B (ApoB), play a important respective roles in estimating metabolic health as well as atherogenic particle burden. These measures should therefore be considered in the context of stroke risk assessment, monitoring, and secondary prevention.

ObjectiveTo synthesize human clinical evidence from systematic reviews and meta-analyses on stem cell-based therapies for ischemic stroke, with an emphasis on mesenchymal stem cell-based interventions, and to appraise their efficacy, safety, methodological quality, overlap, and certainty of evidence.MethodsThis Open Science Framework-registered umbrella review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 and Joanna Briggs Institute guidance. PubMed/MEDLINE, Scopus, and Web of Science were searched through 1 November 2025. Eligible studies were systematic reviews or meta-analyses of randomized or nonrandomized human clinical studies evaluating mesenchymal stem cells or related stem cell-based interventions for ischemic stroke. Two reviewers independently performed study selection, data extraction, AMSTAR 2 (A MeaSurement Tool to Assess systematic Reviews 2) appraisal, and GRADE (Grading of Recommendations Assessment, Development and Evaluation)-based certainty assessment. Because of overlap among reviews and heterogeneity in cell products, administration routes, timing, and outcomes, the findings were synthesized narratively rather than through a de novo meta-analysis.ResultsTwenty-six reviews were included. The evidence suggested possible improvements in neurological impairment, disability, activities of daily living, and motor recovery; however, effect estimates varied according to cell type, administration route, timing after stroke, and follow-up duration. Intravenous administration was the most frequently studied and appeared feasible, with acceptable short-term safety reporting, whereas intra-arterial and intracerebral routes showed greater procedure-related concerns. Short-term adverse events were not consistently increased. However, the evidence remains insufficient regarding rare or delayed risks, including tumorigenesis, ectopic tissue formation, embolic events, and alloimmunogenicity. The certainty of evidence was low to moderate for most efficacy outcomes, moderate for short-term adverse events, and very low to low for long-term or rare safety outcomes.ConclusionsStem cell-based therapies, particularly mesenchymal stem cell-based approaches, may improve selected neurological and functional outcomes after ischemic stroke. However, overlapping reviews, heterogeneous interventions, small early-phase trials, and limited long-term follow-up require cautious interpretation. Adequately powered, standardized, multicenter trials with long-term safety surveillance are needed before routine clinical implementation.