• Drugs and Cell-Based Therapies for the Prevention and Treatment of Neonatal Brain Injury.
    1 week ago
    The international burden of neonatal brain injury (NBI) remains significant with enormous potential for therapeutic intervention. Recent large trials have demonstrated no neuroprotection with either erythropoietin or darbepoetin for term or pre-term brain injury. Neuroprotective strategies with strong evidence are currently limited to antenatal steroids, antenatal magnesium, and supportive care for pre-term NBI and therapeutic hypothermia for term hypoxic-ischemic encephalopathy. Of the pharmacologic strategies currently being investigated clinically, the agents with the highest likelihood of success and closest to clinical implementation include melatonin, topiramate, and stem cell-based therapies. More therapies to prevent or treat NBI are urgently needed.
    Cardiovascular diseases
    Care/Management
  • The Use of Cardiotonic Drugs in Neonates.
    1 week ago
    This overview provides a summary of the commonly used vasoactive agents and the various clinical scenarios in which they are used in the neonatal intensive care unit (NICU). The lack of well-designed clinical trials in this vulnerable population means that these agents continue to be administered without sufficient evidence-based knowledge on their dosing, safety, efficacy and long-term effects. The lack of age appropriate cardiotonic formulations remains an ongoing challenge. Future trials of cardiotonic drugs need to incorporate echocardiography and other objective monitoring tools in their design with robust assessments of short and longer-term outcomes.
    Cardiovascular diseases
    Care/Management
  • Pharmacologic Options for Treatment and Prevention of Hypertensive Disorders of Pregnancy.
    1 week ago
    Hypertensive disorders affect 15% of US pregnancies, significantly contributing to maternal and neonatal morbidity. This paper explores the profound hemodynamic adaptations of pregnancy and how their failure leads to conditions like preeclampsia and gestational hypertension. Diagnosis relies on blood pressure thresholds (≥140/90 mm Hg), with management focusing on preventing severe sequelae. Labetalol and nifedipine are established as first-line treatments due to their safety and efficacy, while angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are strictly contraindicated due to fetotoxicity. Low-dose aspirin is recommended for high-risk patients. Ultimately, early recognition and evidence-based pharmacologic intervention are critical for improving obstetric outcomes.
    Cardiovascular diseases
    Care/Management
  • When Should Anticoagulation Be Started after Major Trauma?
    1 week ago
    The risk of venous thromboembolism following major trauma is high without pharmacologic prophylaxis. The timing of initiation is controversial. It can be delayed, interrupted for procedures, or never initiated due to concern for bleeding from injury sites. Current evidence supports initiation of pharmacologic prophylaxis within 24 hours of admission to reduce the risk of venous thromboembolism. Initiation within 24 hours of admission appears to be safe with low risk of bleeding from injuries, including progression of intracranial hemorrhage.
    Cardiovascular diseases
    Care/Management
  • The impact of benralizumab and dupilumab on exhaled volatile organic compound profiles of severe asthma patients - a preliminary analysis.
    1 week ago
    Volatile organic compounds (VOCs) in exhaled breath reflect biological processes in the lungs. Exploring VOC profiles in severe asthma patients starting biologics may reveal treatment-related biological changes over time. This study aimed to assess the performance and feasibility of applying a sparse partial least squares-discriminant analysis (sPLS-DA) analytical approach in detecting longitudinal changes in exhaled VOCs of patients with severe asthma initiating biologic treatment. Exhaled breath was collected in the 3TR-ABC study, a multicenter observational prospective cohort study, at baseline and 4 months after starting biologics (benralizumab or dupilumab). VOCs were trapped on thermal desorption tubes and analyzed by gas chromatography-mass spectrometry. Paired sPLS-DA was used to distinguish baseline from post-treatment VOC profiles, and Kendall rank correlation assessed associations with clinical parameters at baseline. Data from two sites (Amsterdam and Copenhagen) were available of 25 severe asthma patients. The sPLS-DA resulted in a model containing five VOCs (methyl isobutyl ketone, 2-ethyl-1-hexanol, 5-methyl octadecane, 2-methylundecane and 1,1'-oxybis(decane)) with an area under the receiver operating characteristic curve of 0.89 (95% confidence interval: 0.79-0.99) for distinguishing baseline and 4 months post treatment. At baseline, a positive correlation was observed between 2-ethyl-1-hexanol and asthma control (Asthma Control Questionnaire); τ = 0.40, p < 0.01. A negative correlation was found between 1,1'- oxybis(decane) and blood eosinophil counts (τ = -0.30, p=0.04). Based on our results, the proposed analytical approach appears feasible for analyzing longitudinal data in patients with severe asthma initiating biologics. Further validation in larger cohorts is warranted to confirm robustness and generalizability.
    Cardiovascular diseases
    Care/Management
  • Body mass index, acute atrial fibrillation termination, and long-term recurrence after catheter ablation for persistent atrial fibrillation: insights from a large contemporary cohort.
    1 week ago
    Obesity is a modifiable risk factor for atrial fibrillation (AF), but its relationship with acute procedural response and long-term rhythm durability after ablation for persistent AF (PeAF) remains incompletely defined.

    To evaluate the association of body mass index (BMI) with acute AF termination and long-term atrial arrhythmia recurrence after first-time radiofrequency catheter ablation for PeAF.

    We analyzed prospective data from 7,559 consecutive patients with clinically documented PeAF undergoing first-time radiofrequency catheter ablation between January 2018 and March 2025. Patients were classified according to World Health Organization BMI categories. The primary outcome was atrial arrhythmia recurrence after a 3-month blanking period.

    During a median follow-up of 41 months, atrial arrhythmia recurrence occurred in 3,494 patients (46.2%). In the fully adjusted model, higher BMI was associated with recurrence as a continuous variable (HR 1.03, 95% CI 1.02-1.04). Compared with normal-weight patients, overweight and obese patients had higher recurrence risks (HR 1.15, 95% CI 1.06-1.24; and HR 1.31, 95% CI 1.18-1.45, respectively). Acute AF termination occurred in 832 patients (11.0%) and decreased with increasing BMI. Higher BMI was associated with lower odds of acute AF termination (OR 0.95, 95% CI 0.93-0.97). Findings were consistent across sensitivity analyses.

    In patients with PeAF undergoing first-time radiofrequency ablation, higher BMI was associated with lower acute AF termination and increased long-term recurrence. BMI may serve as a practical marker for preprocedural risk stratification.
    Cardiovascular diseases
    Care/Management
  • Is population-based cardiovascular screening feasible in primary care? Results from the PreveCardio program.
    1 week ago
    Cardiovascular diseases are the leading cause of mortality in Spain, yet there is no systematic population-based cardiovascular screening program. This study evaluated the feasibility of a nurse-led, single-visit cardiovascular screening program in primary care (PreveCardio), and identified the prevalence of modifiable cardiovascular risk factors, their associated socioeconomic factors, and the translation of pilot findings into regional health policy.

    We conducted a cross-sectional study across 42 primary care centers in a Spanish region (January-March 2023). A random sample of 8491 individuals aged 50 to 75 years was invited to participate. Trained nurses performed a single 30-minute visit with point-of-care measurements (blood pressure, lipid profile, HbA1c) and validated questionnaires. Multivariable logistic regression models were fitted with Benjamini-Hochberg correction.

    A total of 3545 individuals participated (41.8%; mean age 61.2 ± 7.3 years; 56.7% women). The completeness of clinical data exceeded 99%. Elevated blood pressure was identified in 40.4%, obesity in 29.5%, nonoptimal low-density lipoprotein cholesterol in 48.7%, prediabetes in 30.7%, and active smoking in 19.5%. Smoking showed the steepest socioeconomic gradient (aOR, 3.25; 95%CI, 2.09-5.03). The direct cost per participant was euro11.75.

    A nurse-led, single-visit cardiovascular screening program is operationally feasible in Spanish primary care, revealing a high burden of modifiable cardiovascular risk factors and significant socioeconomic disparities. Smoking showed the steepest income-associated gradient. This pilot study led to the approval of the first systematic cardiovascular screening program in a Spanish autonomous community.
    Cardiovascular diseases
    Care/Management
  • The role and mechanisms of the cGAS-STING signaling pathway in age-related pathophysiological processes: challenges and therapeutic strategies.
    1 week ago
    Agingis characterized by chronic low-grade inflammation ("inflammaging"), a key driver of functional decline and age-related diseases. The cGAS-STING pathway, which senses cytosolic DNA, has emerged as a central mediator of this sterile inflammation. Here, we systematically review the mechanisms of cGAS-STING activation in aging-including mitochondrial DNA leakage, nuclear envelope disruption, and retrotransposon activation-and its role in driving cellular senescence and the senescence-associated secretory phenotype (SASP). We examine the pathway's pathological contributions across multiple systems, including the nervous, cardiovascular, musculoskeletal, metabolic, reproductive, and sensory systems. We also discuss therapeutic strategies targeting cGAS-STING, encompassing small-molecule inhibitors, natural products, nanomedicine, and gene therapy. Furthermore, we integrate AlphaFold3-based structural modeling and CB-DOCK2 molecular docking analyses to characterize the binding modes and affinities of key inhibitors (e.g., H-151, RU.521, VBIT-4, Mdivi-1) to cGAS, STING, VDAC1, and DRP1, providing a structural rationale for their therapeutic potential. Finally, we address current challenges, including tissue-specific effects and pathway complexity, and highlight future directions for translating these insights into clinical interventions for aging and age-associated disorders.
    Cardiovascular diseases
    Care/Management
  • Gastrointestinal manifestations are common and highly burdensome in patients with adult-onset myotonic dystrophy type 1.
    1 week ago
    Myotonic dystrophy type 1 (DM1) is a progressive, multisystemic disorder in which gastrointestinal (GI) involvement is prevalent but frequently underestimated in routine clinical care. This study aimed to evaluate the GI manifestations and symptom burden in patients with adult-onset DM1. We performed a retrospective study in patients with genetically confirmed adult-onset DM1. GI symptom burden was assessed through three sources: (1) patient-reported outcome measures (PROMs), specifically the Gastrointestinal Symptom Rating Scale (GSRS) and the Sydney Swallow Questionnaire (SSQ), (2) an open-ended question asking patients to name their five most bothersome symptoms, and (3) GI symptoms and diagnoses documented in their medical records. Associations between GI symptoms and sex, age, disease duration, Body Mass Index (BMI), and CTG repeat size were analysed. Ninety-five patients with adult-onset DM1 were included (57% female; mean age 44.2±11.8 years). GI symptoms imposed a substantial burden, as 54% of patients exceeded the GSRS clinical threshold and 53% exceeded the SSQ threshold. In open-ended reporting, 31% of patients named a gastrointestinal problem among their most bothersome symptoms, ranking it fourth among all complaints, 13% named swallowing difficulties. In line with the PROM findings, medical record review demonstrated a high prevalence of GI manifestations, including dysphagia (59%), diarrhoea (35%), and constipation (33%). Female sex was strongly associated with higher odds of constipation (OR 9.25,p<0.01), diarrhoea (OR 3.45,p=0.02), and abdominal pain (OR 7.40,p<0.01). Increasing age and longer disease duration were associated with higher odds of constipation, dysphagia, cholelithiasis, and non-alcoholic liver steatosis (p<0.05). No associations were observed for CTG repeat size or BMI. GI symptoms are highly prevalent and burdensome in adult-onset DM1. Female sex, longer disease duration, and older age were associated with a higher symptom prevalence. Structured screening using PROMs should be integrated into multidisciplinary care to ensure that these symptoms are detected promptly and addressed adequately.
    Cardiovascular diseases
    Care/Management
  • Intraoperative monitoring of anesthetic drugs in patient plasma via a SERS-based sensing platform.
    1 week ago
    Conventional clinical monitoring of anesthetic agents predominantly relies on indirect physiological indicators, which fail to accurately quantify the actual anesthetic concentrations in circulating blood. We report a surface-enhanced Raman spectroscopy (SERS) sensing platform based on TiO₂@Ag nanocomposites, coupled with optimized solid-phase extraction pretreatment, for the semi-quantitative trend monitoring of anesthetic drugs in complex blood matrices. This platform achieves reliable detection across the clinically relevant concentration range (nanomolar to micromolar levels), enabling concentration-dependent detection of four widely used clinical anesthetic agents with excellent reproducibility. Validation with authentic clinical blood samples further confirms a significant correlation between recorded SERS signals and LC-MS/MS-determined laudanosine concentrations, together with physiologically consistent trends in pharmacodynamic responses. Collectively, these proof-of-concept findings support the preliminary feasibility of SERS-based intraoperative anesthetic monitoring, warranting further validation toward future perioperative drug monitoring applications.
    Cardiovascular diseases
    Care/Management