Viruses are increasingly recognized as potential modulators of oral biofilm ecology and periodontal inflammation, expanding the traditional bacterial paradigm of periodontitis. Members of the Herpesviridae family, including Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), and herpes simplex virus (HSV), are frequently detected in periodontal tissues and may influence disease activity through latency, reactivation, immune modulation, epithelial barrier disruption, and interactions with bacteria. These processes may contribute to local dysbiosis and sustained periodontal inflammation. The potential systemic relevance of oral viruses is biologically plausible but remains incompletely established. Viral persistence or reactivation in oral niches may contribute to systemic immune activation through hematogenous spread, saliva-mediated dissemination, aspiration, or amplification of inflammatory mediators as IL-1β, IL-6, and TNF-α. Accordingly, viruses may act as disease modifiers within the broader relationship between periodontitis and systemic conditions including cardiovascular, metabolic, respiratory, neurogenerative, pregnancy-related, and cancer-associated outcomes. However, the strength of evidence differs across these conditions. Current data support a model in which oral viruses, bacteriophages, bacteria, and fungi form an interconnected biofilm ecosystem that may influence periodontitis progression and systemic inflammatory burden. Nevertheless, most available evidence is observational, associative, or derived from mechanistic experimental models, and definitive proof that viruses are independent etiopathogenic drivers of periodontitis is lacking. Future longitudinal and interventional studies are needed to determine whether viral detection reflects bystander association, disease amplification, or a true pathogenic role, and whether antiviral or phage-based strategies offer clinical benefit beyond established periodontal therapy.

Inflammatory diseases represent a major global health burden, and current therapies frequently fail to achieve sustained control of inflammation or prevent progressive tissue damage. Cortistatin (CST), an endogenous neuropeptide structurally related to somatostatin, has emerged as a multifunctional regulator of neuroimmune and immunometabolic pathways.

This scoping review was conducted in accordance with PRISMA-ScR guidelines and maps and synthesizes preclinical evidence on the biological roles and therapeutic potential of CST across experimental disease models.

A comprehensive literature search identified 31 preclinical studies published between 2006 and 2025 that evaluated CST administration or cortistatin deficiency. Despite substantial heterogeneity in disease models, including neurodegenerative, autoimmune, cardiovascular, fibrotic, and musculoskeletal conditions, CST consistently demonstrated protective effects. Across studies, CST reduced pro-inflammatory cytokine production, attenuated tissue damage, and improved functional outcomes and survival. Mechanistically, CST modulated key inflammatory pathways such as NF-κB signaling and NLRP3 inflammasome activation, suppressed Th1 and Th17 responses, and promoted regulatory T cell expansion through interactions with somatostatin receptors, GHSR1a, and MrgX2. Emerging translational strategies, including peptide analogues, protease-activated prodrugs, and nanoparticle-based delivery systems, have improved pharmacokinetic stability and therapeutic efficacy in experimental models.

Collectively, these findings establish cortistatin as a consistent endogenous regulator of neuroimmune responses across diverse experimental conditions, highlighting its potential as a promising therapeutic target for immunomodulation in complex inflammatory diseases.

Dilated cardiomyopathy (DCM) and left ventricular non-compaction (LVNC) are major non-ischemic cardiomyopathy (NICM) subtypes with heterogeneous outcomes. Conventional clinical and echocardiographic markers remain insufficient for long-term risk stratification.

This study aimed to identify serum metabolites associated with adverse cardiovascular outcomes and evaluate their incremental prognostic value in NICM.

Thirty-two patients with DCM or LVNC and left ventricular ejection fraction < 50% were enrolled and followed for a median of 45.5 months. The primary endpoint was a composite of cardiovascular death, heart failure-related hospitalization, or clinically indicated cardiovascular device implantation. Baseline serum samples underwent liquid chromatography-mass spectrometry-based untargeted metabolomic profiling. Differential metabolites were identified using OPLS-DA and KEGG enrichment analysis. Prognostic metabolites were screened using Cox regression, Kaplan-Meier analysis, correlation filtering, and ROC analysis. An integrated Cox model combining clinical and metabolic markers was evaluated using bootstrapping, calibration, and time-dependent ROC analysis.

A total of 299 differential metabolites were identified and enriched in bile secretion, steroid hormone biosynthesis, and neuroactive ligand-receptor interaction pathways. Sphingosine-1-phosphate (S1P) and tetrahydrocortisone (THE) were selected as final prognostic metabolite biomarkers, with ROC AUCs of 0.777 and 0.793, respectively. The integrated model incorporating S1P, THE, tricuspid annular plane systolic excursion, and total protein achieved a bootstrap-corrected C-index of 0.772, with time-dependent AUCs of 0.92 and 0.86 at 3 and 5 years.

Serum metabolomics may provide complementary prognostic information in NICM. S1P and THE are exploratory biomarkers linked to remodeling and stress, supporting risk stratification in NICM with reduced ejection fraction.

To evaluate real-world use of advanced cardiovascular imaging in less common and rare rheumatic immune-mediated inflammatory diseases (IMIDs) and identify variation in practice to inform future studies and clinical guidelines.

A retrospective, multi-centre quality improvement project was conducted across four major hospitals in the UK. Adults with systemic lupus erythematosus, systemic sclerosis, inflammatory myopathy, vasculitis or primary Sjögren's disease who underwent cardiac magnetic resonance (CMR), CT coronary angiography (CTCA) or positron emission tomography (PET) between January 2023 and December 2024 were included. Demographics, underlying IMID, cardiovascular risk factors, imaging indications, findings and management were extracted using a standardised proforma and analysed.

A total of 294 imaging studies were performed in 261 patients (72.4% female, 65.9% aged 40-74 years) comprising 137 (46.6%) CMR, 40 (13.6%) CTCA, and 117 (39.8%) PET scans. Indications varied by modality and centre. Cardiovascular abnormalities were reported in 175/294 (59.5%), most commonly in vasculitis (53.7%). Notably, 54/63 (85.7%) of abnormal PET and 61/89 (68.5%) of abnormal CMR scans were in asymptomatic patients. Imaging findings prompted cardiology referral/ongoing follow-up in 59.5% and changes to IMID treatment in 31.3%, but only 23.1% were discussed in a formal multidisciplinary team (MDT).

Advanced cardiovascular imaging frequently identifies cardiovascular involvement in rheumatic IMIDs, including in asymptomatic patients. Treatment adjustments occurred in a third of patients, although largely undertaken outside established MDT processes. These findings emphasise the need for better understanding of imaging-based findings and for cardio-rheumatology MDTs to support integrated decision-making to improve patient outcomes.

The Kirsten rat sarcoma viral oncogene homolog (KRAS) is one of the most frequently mutated oncogenes and is associated with poor prognosis. Long considered an undruggable target, KRAS has recently become actionable with the development of direct inhibitors, particularly against the G12C mutation. Our group previously reported promising efficacy and safety results for glecirasib (JAB-21822), a novel KRAS^G12C inhibitor, in phase I/II trials involving solid tumors harboring KRAS^G12C mutations (ClinicalTrials.gov NCT05009329, NCT05194995). Nevertheless, primary (5.61%) and acquired (9.64%) resistance were observed. This study analyzed 18 patients with advanced solid tumors harboring the KRAS^G12C mutation from the JAB-21822 cohort. Longitudinal blood samples (N = 45) were collected at baseline, during partial response or stable disease, and at disease progression. Circulating tumor cells (CTCs) were isolated via a microfluidics platform (CTC100, Cellomics) and categorized into epithelial (E-CTCs), mesenchymal (M-CTCs), and epithelial/mesenchymal mixed (E/M-CTCs) subtypes. At progression, the proportion of E-CTCs showed a decreased trend, while that of E/M-CTCs increased significantly (p = 0.03). In long-term responders, the inflection points of declining M-CTC levels correlated with clinical progression and were consistent with radiographic outcomes. Baseline CTC counts > 1 were associated with shorter progression-free survival (PFS; p = 0.046). E-CTC ≤ 1 correlated with longer PFS (p = 0.025), and M-CTC ≤ 1 with longer overall survival (OS; p = 0.033). E/M-CTC ≤ 1 showed a trend toward improved OS (p = 0.086). In addition, patients with > 1 CTC who received local radiotherapy for progressive lesions after glecirasib targeted therapy had significantly prolonged PFS and OS compared to those who did not (p < 0.05).

Stroke remains a major cause of disability and mortality globally, particularly among older adults in low- and middle-income countries. Integrating the 4Ms framework (What Matters, Medication, Mentation, and Mobility) into nursing-led preventive interventions offers a holistic, person-centered model for promoting healthy aging and mitigating stroke risk. This study evaluated the effectiveness of a nurse-led, age-friendly educational program, grounded in the 4Ms framework, in reducing stroke risk and enhancing health-promoting behaviors among older adults. A randomized controlled trial was conducted with 170 community-dwelling adults (≥ 60 years) attending outpatient clinics in Egypt. Participants were randomized to either a 4Ms-based educational intervention (two structured sessions and materials) or a control group receiving routine care. Outcomes were measured using the Revised Framingham Stroke Risk Profile, the Health-Promoting Lifestyle Profile II, and a stroke prevention practices questionnaire. Post-intervention, the intervention group demonstrated a significant reduction in 10-year stroke risk scores (p<.001) and significant improvements across all health-promoting behavior domains, especially physical activity, nutrition, and stress management (all p<.001). The percentage of participants with good stroke-prevention practices increased from 7.1% to 55.3%. Stroke risk was also inversely correlated with domains like health responsibility and stress management. The nurse-led educational program based on the 4Ms framework was associated with short-term improvements in reducing stroke risk indicators and improving health-promoting behaviors among older adults. Integration of age-friendly principles into preventive nursing care may offer a feasible and holistic approach for supporting healthy ageing in low-resource settings. Longer-term studies remain necessary.Trial RegistrationPan African Clinical Trials Registry (PACTR), registration number PACTR202606898663018. Registration was completed retrospectively.

Classical galactosemia (CG), caused by galactose-1-phosphate uridylyltransferase (GALT) enzyme deficiency, is associated with premature ovarian insufficiency (POI) and subfertility. The last years, a counseling paradigm shift has been advocated with emphasis on subfertility instead of infertility because spontaneous pregnancy can occur.

We describe two women (aged 26 and 30 years) with genetically confirmed CG and POI, who conceived spontaneously. Both adhered to lifelong galactose-restricted diet and had regular endocrine monitoring. Their pregnancies were uncomplicated and each delivered a healthy infant at term.

These cases are in line with the counseling paradigm shift, with natural conception being possible in CG. Reproductive counselling of girls and women with CG should entail fertility preservation and spontaneous pregnancy. In case of desired pregnancy, a period of two years to attempt conceiving should be advised. AMH is not a reliable prognostic parameter for predicting the reproductive potential in CG.

Obstructive hypertrophic cardiomyopathy (HCM) is defined by left ventricular hypertrophy with outflow tract obstruction. Despite clear guideline-directed medical therapy recommendations from the European Society of Cardiology (ESC), it remains unclear whether real-world treatment aligns with these guidelines. This study evaluates adherence to ESC guidance in Germany, focusing on pharmacological and invasive therapies and identifying gaps in real-world care for patients with obstructive HCM.

A retrospective cohort analysis was conducted using the WIG2 Benchmark database, containing administrative claims data from German statutory health insurers. Patients aged ≥18 years who received an International Classification of Diseases (ICD)-coded diagnosis of HCM between 2012 and 2018 were included. Treatment alignment was assessed against ESC guidelines on HCM.

Of 6793 patients with an HCM diagnosis, 1141 had obstructive HCM. Mean age was 59.7 years and 62% were male. Following initial HCM consultation, 18% received beta-blocker (BB) monotherapy and 12% received calcium channel blocker (CCB) monotherapy, in accordance with ESC guidelines. However, 43% of treatment combinations were not aligned with the ESC guidelines, including use of contraindicated dihydropyridine CCBs and vasodilating BBs, and 22% of patients did not receive any HCM-related pharmacological treatment. Overall, only 57% of the prescribed treatments were consistent with ESC guidelines for obstructive HCM management.

This study reveals substantial gaps in alignment with the ESC guidelines for obstructive HCM management in Germany, underscoring the need for enhanced clinician education on existing therapies. Greater uptake of guideline-directed medical therapy is critical to improving patient well-being, functional status and outcomes.

Cardiovascular diseases remain to be the leading cause of death in the Philippines. Screening may lead to improvement of clinical outcomes if such conditions are detected and managed early and appropriately. The benefits of screening for a particular disease must be balanced with potential harms due to mislabeling or adverse effects of treatment, as well as socio-economic implications in the primary care setting. The main objective of this clinical practice guideline initiated by the Department of Health and the National Institutes of Health is to provide evidence-based recommendations that will help primary care physicians in detecting selected cardiovascular diseases among apparently healthy, asymptomatic individuals, while considering the socio-economic implications of the diagnostic screening tests.

We performed a systematic synthesis of evidence to address screening for six priority cardiovascular conditions among asymptomatic, apparently healthy adult Filipinos: 1) familial hypercholesterolemia, 2) coronary artery disease, 3) asymptomatic carotid artery stenosis, 4) peripheral arterial disease, 5) abdominal aortic aneurysm, and 6) atrial fibrillation. We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to CPG development recommended by the Department of Health. The process included 1) generation of critical questions and critical outcomes, 2) retrieval of current and relevant evidence, 3) synthesis and assessment of the evidence base for these critical questions, 4) formulation of draft recommendations, 5) convening of a multisectoral stakeholder panel to discuss feasibility, values, and preferences, and assess the strength of the recommendations, and 6) planning for dissemination, implementation, impact evaluation, and updating.

The CPG provides seven recommendations on six prioritized questions in the screening for certain cardiovascular disorders. After presentation of the evidence by the evidence reviewer experts and deliberation by the consensus panel, we came up with two statement recommendations for the question on screening for abdominal aortic aneurysm and one statement recommendation each for the rest of the clinical questions. The consensus panel made strong recommendations to screening for two conditions in asymptomatic and apparently healthy Filipinos, namely: familial hypercholesterolemia and abdominal aortic aneurysm (moderate).

Among asymptomatic, apparently healthy adult Filipinos, we recommend routine screening for two cardiovascular conditions: familial hypercholesterolemia and abdominal aortic aneurysm, with the latter being applicable only to men 60-80 years of age. These recommendations are offered to guide the primary care physician in screening key cardiovascular diseases and should not supplant but rather supplement the healthcare provider's sound clinical judgment.

This study characterized the clinical and genetic features of Danon disease (DD), focusing on participants harboring LAMP2 frameshift variants at the 325th amino acid position (p.Leu325fs), and explored their cardiac implications. These frameshift variants result in loss of functional LAMP2 protein through premature termination, thereby impairing lysosomal function. Although the association between LAMP2 variants and DD is established, the cardiac phenotype specifically associated with p.Leu325fs variants remains incompletely characterized.

We conducted a retrospective analysis of nine patients with DD diagnosed at the Fuwai Hospital of the Chinese Academy of Medical Sciences, Beijing, China. Comprehensive clinical data, including biochemical markers, electrocardiographic findings, and imaging studies (echocardiography and cardiac magnetic resonance imaging), were collected. Pathogenic LAMP2 variants were confirmed through exome sequencing or clinical genetic testing.

All participants carried pathogenic frameshift variants at p.Leu325fs, presenting with prominent cardiac manifestations including myocardial hypertrophy or dilation, impaired systolic function, and arrhythmias. Electrocardiographic abnormalities, notably intraventricular conduction block and ST-T segment changes, were observed in all participants. Elevated N-terminal prohormone of brain natriuretic peptide and lactate dehydrogenase levels were observed in all participants, consistent with advanced heart failure and myocardial injury.

Our findings suggest that p.Leu325fs pathogenic variants in DD are associated with a predominantly cardiac phenotype, characterized by universal intraventricular conduction block, ST-T segment changes, progressive myocardial fibrosis, and impaired systolic function. These results support the clinical value of integrating LAMP2 genetic testing, cardiac MRI, and electrocardiographic monitoring into the early diagnosis, risk stratification, and management of patients with DD.