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PubMed2026

Empagliflozin and functional aerobic capacity in individuals with increased risk of heart failure: The Empire Prevent Cardiac trial.

BACKGROUND: Higher maximal oxygen consumption (VO₂ max) is associated with lower risk of developing heart failure (HF). Empagliflozin improves VO2 max in HF with reduced ejection fraction, but the effect on VO2 max in individuals at risk of HF remain unknown. OBJECTIVE: This study aimed to evaluate the effect of 180 days treatment with empagliflozin compared to placebo on VO2 max, daily physical activity level, and quality of life (QoL) in individuals with overweight or obesity and risk of HF. METHOD: This investigator-initiated, double-blinded, randomized, placebo-controlled, multicenter trial included elderly individuals with body mass index >28 kg/m2 and at least one additional risk factor for HF, including hypertension, ischemic heart disease, stroke, or chronic kidney disease. Individuals with HF or type 2 diabetes mellitus were excluded. The primary endpoint was the mean difference in change of VO2 max. The secondary outcome was objectively measured physical activity level. QoL was an explorative outcome. RESULTS: Among 191 randomized individuals (94 empagliflozin, 97 placebo), 89% had hypertension and 66% ischemic heart disease. At baseline, 69% were male, median age was 68 years, median body mass index 31.9 kg/m², mean left ventricular ejection fraction 65 ± 9%, and mean VO₂ max 18.1 ± 4.3 mL/min/kg. Empagliflozin did not change VO2 max with an estimated treatment difference of -0.2 mL/min/kg (97.5% confidence interval -1.2 to 0.8), adjusted P = 1.00. No significant treatment differences were observed for neither daily physical activity nor QoL. CONCLUSIONS: Empagliflozin did not affect VO2 max, physical activity level, or QoL in elderly individuals with overweight or obesity and risk of HF.

Humans↗

PubMed2026

Impact of estimated total blood volume on NT-proBNP response to angiotensin receptor-neprilysin inhibition in acute heart failure: Insights from the PREMIER study.

BACKGROUND: Sacubitril/valsartan (Sac/Val) reduces N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in acute heart failure (AHF), particularly in patients with reduced ejection fraction. However, whether estimated total blood volume (TBV), calculated using anthropometric equations, is associated with heterogeneity in biomarker response remains uncertain. METHODS: This post hoc exploratory sub-analysis of the PREMIER randomized trial evaluated whether baseline estimated TBV was associated with heterogeneity in NT-proBNP reduction after Sac/Val compared with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) therapy. Estimated TBV was calculated using validated anthropometric equations and dichotomized at the median (4.05 L). Patients were further stratified by left ventricular ejection fraction (LVEF <40% vs ≥40%). The primary endpoint was the proportional change in NT-proBNP from baseline to Week 8. RESULTS: Among 376 patients, 372 with baseline estimated TBV data were analyzed. In the high TBV group, Sac/Val was associated with greater NT-proBNP reduction than ACEI/ARB (-56% vs -32%; ratio of change, 0.67; 95% confidence interval, 0.53-0.84; P = .001), whereas no significant difference was observed in the low TBV group (P for heterogeneity = 0.063). In patients with LVEF <40%, Sac/Val was associated with greater NT-proBNP reduction in both TBV groups. In patients with LVEF ≥40%, Sac/Val was associated with greater NT-proBNP reduction in the high TBV group, whereas the point estimate in the low TBV group numerically favored ACEI/ARB. CONCLUSIONS: In this exploratory post hoc analysis, higher estimated TBV was associated with greater NT-proBNP reduction after Sac/Val, particularly among patients with LVEF ≥40%. These findings are hypothesis-generating and require external validation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05164653; Japan Registry of Clinical Trials, jRCTs021210046.

Humans↗

PubMed2026

Maternal obesity in rats results in male-specific increases in genome-wide DNA methylation in postnatal offspring liver.

Male-specific peripubertal DNA demethylation in the liver has been reported in mice. Here, we investigated whether it also occurs in rats, the influence of maternal obesity and whether DNA demethylation changes contribute to observed sex-specific effects of maternal obesity in offspring. Female rats were fed a high-fat, high-sugar 'cafeteria' (Caf) diet before mating with standard chow-fed males. The offspring liver methylome and transcriptome were examined. Body weight was higher in Caf-fed dams prior to mating, during gestation and at parturition. Male and female offspring from Caf-fed dams had lower birth weights but higher adult weights and adiposity than offspring from chow-fed dams. A comparison of DNA methylation in 3-week-old weaner males versus female siblings from chow-fed dams did not reveal the male-specific DNA demethylation that was previously reported in mice. However, strong maternal diet effects in male weaner offspring methylation were observed. A comparison of female weaners from chow- versus Caf-fed dams showed a range of differences, with 39% of differentially methylated regions (DMRs) having higher methylation in Caf offspring and 61% of DMRs having higher methylation in chow offspring. In stark contrast, 99% of maternal-diet-induced DMRs in male weaner offspring had higher methylation in offspring from Caf-fed dams. This suggests that maternal obesity induces widespread hypermethylation in the male offspring liver at weaning. However, a comparison with RNA sequencing data revealed limited transcriptional changes at this developmental stage or in adult offspring. While these data highlight how environmentally sensitive DNA methylation is in the male rodent perinatal period, these methylation changes may not be a major contributor to sex differences in developmentally programmed liver disease.

Animals↗

PubMed2026

High-Flow Nasal Oxygen Versus Conventional Oxygen Therapy and Non-Invasive Ventilation for Acute Respiratory Failure in the Emergency Department: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis compares the use of high-flow nasal oxygen (HFNO) with conventional oxygen therapy (COT) and non-invasive ventilation (NIV) in the management of acute respiratory failure (ARF) in the emergency department (ED). A comprehensive search of relevant sources was undertaken. Randomised controlled trials (RCTs) assessing adult patients (≥ 18 years) treated in the ED for ARF and comparing HFNO to COT/NIV were included. The primary outcome was the need for endotracheal intubation and mechanical ventilation (IMV). Secondary outcomes included physiological and biochemical parameters, ICU admission, hospital length of stay, dyspnoea scores and mortality. A total of 17 RCTs (1955 patients) were included. There was a significant reduction in IMV favouring the HFNO group compared to COT and NIV (RR 0.64, 95% CI 0.47-0.88). HFNO showed significant improvements in RR, SpO2, PaO2 and Modified Borg Dyspnoea Scale. Subgroup analysis showed reduced rates of IMV with HFNO compared to COT (RR 0.61, 95% CI 0.41-0.91), but not compared to NIV (RR 0.69, 95% CI 0.42-1.14). HFNO additionally showed a reduction of IMV compared to NIV and COT in undifferentiated patients (RR 0.61, 95% CI 0.41-0.93), but not in exacerbations of COPD or acute heart failure. Ten of the 17 studies had at least some concern for risk of bias, with several analyses having notable heterogeneity. HFNO showed a significant reduction in rates of IMV, improvement in peripheral oxygen saturations, PaO2, respiratory rate and patient dyspnoea scores compared to COT and NIV.

Humans↗

PubMed2026

Transcriptomic analysis reveals the molecular mechanisms underlying the inhibition of Mytilus edulis attachment by biofouling control agents.

This study combined acute toxicity assays, phenotypic quantification, and transcriptomic profiling to systematically investigate the inhibitory effects and molecular regulatory mechanisms of a novel alkylamine-based antifouling agent on survival, byssus secretion, and attachment behavior of juvenile Mytilus edulis. The 96 h-LC50 of the agent to juvenile M. edulis was 8.84 mg/L, and 10 mg/L of the agent completely inhibited mussel attachment within 24 h, significantly reducing byssal thread number, length, and diameter while increasing detachment frequency, resulting in irreversible attachment failure. Transcriptomic analysis identified 2746 differentially expressed genes, which were mainly enriched in pathways including signal transduction, immune defense, stress response, cytoskeleton organization, and protein binding. KEGG and GSEA enrichment revealed that the antifouling agent activated the MAPK stress signaling pathway, disturbed transcriptional regulation, and impaired intracellular homeostasis and cytoskeletal stability, thereby synergistically suppressing the expression of key byssal protein genes including mfp-1 and mfp-3 and ultimately blocking byssus synthesis and adhesion. This study clarifies the multi-pathway molecular mechanism underlying antifouling agent-induced attachment inhibition in M. edulis, and provides core molecular targets and theoretical support for developing efficient, specific antifouling activity, and potentially applicable marine antifouling technologies.

Animals↗

PubMed2026

Sex-dependent protective effects of microglial tumor necrosis factor on post-stroke inflammation and myelin injury.

Tumor necrosis factor (TNF) is rapidly induced after ischemic stroke, but its proposed cell-specific and sex-dependent functions during post-stroke inflammation remain insufficiently understood. Here, we investigated the role of microglia-derived TNF in the acute and subacute response to permanent middle cerebral artery occlusion (pMCAO). Tnf expression was transiently upregulated after stroke, becoming significant at 4 h, peaking at 12-24 h, and returning to baseline by 5 days. In situ hybridization confirmed strong Tnf expression in the infarct and peri-infarct regions. Whole-brain transcriptomic profiling showed that global TNF deficiency reshaped the early post-ischemic response, shifting it from microglia-associated phagocytic and wound-healing pathways toward an interferon-related inflammatory signature. To define the specific contribution of microglial TNF, we used inducible Cx3cr1CreER:Tnffl/fl mice. Microglial TNF deletion had no effect on infarct volume in males at 24 h or 5 days after pMCAO, but significantly increased infarct size in females at both time points. In both sexes, brain TNF levels peaked at 24 h and were significantly reduced in Cx3cr1CreER:Tnffl/fl mice, confirming microglia as a major source of early post-ischemic TNF. However, downstream consequences diverged by sex. At 5 days, male Cx3cr1CreER:Tnffl/fl mice showed reduced microglial reactivity and 18 kDa translocator protein (TSPO) signal, with no change in T-cell infiltration, and exhibited increased density of mature oligodendrocytes. In contrast, female Cx3cr1CreER:Tnffl/fl mice displayed enhanced microglial reactivity, increased TSPO binding, higher peri-infarct T-cell infiltration, and reduced oligodendrocyte density and myelin integrity. Together, these findings identify microglial TNF as a sex-dependent regulator of post-stroke inflammation and myelin injury.

Animals↗

PubMed2026

Comparison of Iodinated Contrast Doses Based on Total Body Weight and Lean Body Weight in Pediatric Patients: Impact on Image Quality and Contrast Exposure.

INTRODUCTION: Iodinated contrast dosing in pediatric computed tomography (CT) traditionally relies on total body weight (TBW), which may result in excessive contrast administration, particularly in patients with higher adiposity. Lean body weight (LBW)-based protocols have shown promise in adults but remain underexplored in children. Therefore, the aim of this study was to compare contrast volume requirements and hepatic enhancement quality among three dosing protocols: LBW-based, TBW-based, and the Control Group (CG), based on the institutional standard for pediatric abdominal CT. METHODS: This prospective study enrolled 66 patients (age 0-16 years) undergoing contrast-enhanced abdominal CT between September 2023 and August 2024. Patients were randomly assigned to receive iodinated contrast (iobitridol 350mg I/mL) dosed by: (1) LBW (0.63 g iodine/kg x LBW, calculated using Peters formula; n = 23), (2) TBW (0.46 g iodine/kg x TBW; n = 20), or (3) institutional control protocol (2 mL/kg x TBW, equivalent to 0.7 g iodine/kg; n = 23). Kruskal-Wallis, ANOVA, Two-way ANOVA, ANCOVA, Scheirer-Ray-Hare, and Cohen's Kappa tests with Likert scale were used. RESULTS: The LBW group received lower median contrast volumes (27 mL; IQR, 10-80 mL) compared to the TBW group (34.5 mL; IQR, 18-78 mL) and the CG group (40 mL; IQR, 13-80 mL), although the differences did not reach statistical significance (P > 0.05). Notably, this reduction did not compromise hepatic enhancement, which remained comparable to the CG (552 ± 139 HU; P = 0.107). CONCLUSION: Lean body weight may be a useful parameter for estimating contrast dose in pediatric abdominal CT, potentially reducing administered volumes without compromising diagnostic image quality. IMPLICATIONS FOR PRACTICE: These results provide early evidence that LBW-based dosing may support more individualized contrast administration in pediatric CT, potentially reducing exposure-related risks.

Humans↗

PubMed2026

A First-in-Japanese Phase 1, Double-Blind, Placebo-Controlled, Parallel-Cohort Study of Sefaxersen, an Antisense Oligonucleotide Targeting Complement Factor B, in Healthy Participants.

Increased activity in the complement alternative pathway (AP) plays a key role in diseases such as IgA nephropathy (IgAN). This first-in-Japanese double-blind Phase 1 study investigated the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of sefaxersen (RO7434656), an antisense oligonucleotide targeting complement factor B messenger RNA. Healthy participants were randomized equally into four cohorts: placebo or sefaxersen 20, 40, or 70 mg. The PK, PD, and safety endpoints were monitored throughout the study and during the 90-day follow-up period. All 24 participants completed the study, with no new safety signals or clinically meaningful changes in blood chemistry, electrocardiogram, or vital signs observed. Plasma sefaxersen concentration demonstrated a biphasic PK profile, characterized by an initial rapid decline followed by a slow elimination. Sefaxersen decreased PD markers related to the complement AP selectively, without affecting the classical pathway, in a dose-dependent manner, and the PD effects persisted over 2 to 3 months. Sefaxersen was well tolerated by healthy Japanese participants, with a manageable safety profile. These findings support the inclusion of Japanese patients with IgAN in the global Phase 3 study (IMAGINATION, NCT05797610).

Humans↗

PubMed2026

From pathobiology to prescribing in obesity-driven HFpEF: A systematic review and practical therapeutic framework.

Heart failure with preserved ejection fraction (HFpEF) is increasingly driven by obesity and cardiometabolic dysfunction. In this phenotype, the dominant biology extends beyond congestion alone and includes visceral and epicardial adiposity, systemic inflammation, impaired myocardial energetics, endothelial dysfunction, and exertional elevation in filling pressures. We performed a PRISMA-compliant systematic review with structured narrative evidence synthesis to evaluate pharmacological therapy in obesity-driven HFpEF, searching PubMed/MEDLINE, Scopus, Web of Science Core Collection, ClinicalTrials.gov, and WHO ICTRP through December 2025. Eighteen reports were included in the final qualitative synthesis. The available evidence supports sodium-glucose cotransporter 2 inhibitors as the pharmacological foundation because they provide the most mature outcome data across the preserved ejection fraction spectrum. Semaglutide improves symptoms, physical limitations, exercise capacity, and body weight in dedicated obesity-related HFpEF trials, whereas tirzepatide extends this signal by improving clinical status and reducing worsening heart failure events. Finerenone broadens the therapeutic platform in HF with mildly reduced or preserved ejection fraction, although obesity-specific data remain indirect. Conventional neurohormonal therapies retain a selective role, but they are not the principal biological match for this phenotype. Obesity-driven HFpEF should therefore be managed as a cardiometabolic syndrome with heart failure expression, using a phenotype-based sequence that links diagnosis, decongestion, SGLT2 inhibition, obesity-directed therapy, and selective adjunctive intensification.

Humans↗

PubMed2026

Effects of transcutaneous electrical acupoint stimulation versus acupressure on the trajectories of multidimensional adverse reactions to chemotherapy in breast cancer patients: a secondary analysis of a randomized controlled trial.

BACKGROUND: Chemotherapy for breast cancer often induces multidimensional adverse reactions such as nausea and vomiting, anxiety, depression, and sleep disturbances. These symptoms are interrelated and may evolve dynamically, impacting patients' treatment outcomes and quality of life. As non-pharmacological interventions, transcutaneous electrical acupoint stimulation (TEAS) and self-acupressure (SA) have shown potential in alleviating symptoms. However, their long-term effects on the joint developmental trajectories of these multidimensional symptoms (nausea and vomiting, anxiety, depression, and sleep disturbances) remain unclear. OBJECTIVE: This study aimed to identify potential trajectory class of multidimensional adverse reactions in breast cancer patients undergoing chemotherapy and to explore the differential effects of TEAS and SA on different trajectory subgroups. METHODS: This was a secondary analysis of a randomized controlled trial. A total of 189 breast cancer patients receiving chemotherapy were included. The Group-Based Multi-Trajectory Model (GBMTM) was employed to identify joint developmental trajectories of acute/delayed chemotherapy-induced nausea and vomiting (CINV), anxiety, depression, and sleep quality during chemotherapy. Subsequently, causal forest was used to analyze the average treatment effects (ATE) of TEAS (vs. control group) and SA (vs. control group) on patients' symptom trajectory. RESULTS: Multidimensional adverse reactions were classified into two heterogeneous trajectories: a "High Symptom Burden-Persistent (HSBP)" type (n = 101) and a "Low Symptom Burden-Relieving (LSBR)" type (n = 88). The persistent high incidence of acute CINV contrasted sharply with the comprehensive relief of other symptoms in the latter group. Causal forest suggested that both TEAS and SA significantly increased the probability of patients being classified into the "LSBR" trajectory. The ATE was 0.147 (95% CI: 0.143, 0.151) for TEAS, slightly lower (P < 0.05) than 0.176 (95% CI: 0.162, 0.190) for SA.  CONCLUSION: Multidimensional adverse reactions in breast cancer patients undergoing chemotherapy exhibit heterogeneity in their trajectories. Both TEAS and SA were associated with a higher probability of patients being classified into a more favorable symptom trajectory-LSBR. The multidimensional trajectory identification with treatment effect estimation may serve as a useful analytical strategy for future longitudinal research in cancer chemotherapy-induced adverse reactions symptom management. CLINICAL TRIAL REGISTRATION: ChiCTR2300077667 (Chinese Clinical Trial Registry, https://www.chictr.org.cn/ ), Registered 15 November 2023.

Humans↗

PubMed2026

Evolutionary diversification of invertase paralogs couples carbon metabolism and sexual reproduction in fission yeasts.

Dynamic patterns of gene gain and loss play a major role in the diversification of eukaryotes, reflecting adaptation to a broad range of ecological contexts. Reconstructing the evolutionary history of genes provides a powerful framework for understanding how functional innovation shapes life-history traits. Here we report a comprehensive analysis of gene gain and loss across the fission yeast clade, whose evolutionary trajectory remains elusive. Reductive evolution of metabolic genes is a major contributor to species diversification, as observed in other fungal taxa. Notably, we uncovered an evolutionary scenario in which an ancestral gene duplication was followed by lineage-specific loss of one or the other paralog, except in S. pombe, which retained both. We demonstrate that these paralogs encode catalytically-active invertases, named Inv1 and Inv2, with distinct enzymatic properties, localization, regulation, and physiological roles. Inv1 is a secreted enzyme subject to glucose catabolite repression and is the sole invertase required for sucrose assimilation, resembling canonical yeast invertases. In contrast, Inv2 is intracellular, constitutively expressed, and required for inducing sexual differentiation in response to nutrient availability. Overall, these findings reveal an unexpected role for carbon metabolism in modulating the haploid-diploid cycle of fission yeasts, suggesting that diversification of core metabolic functions may contribute to adaptation to environments with distinct sugar compositions.

Evolution↗

PubMed2026

Chronic neurological diseases with acute respiratory failure in a real-life cohort: insights into ICU and long-term survival-A retrospective study.

BACKGROUND: Patients with chronic neurological diseases (CND) are at increased risk of pulmonary complications that often require ICU admission. This study aimed to identify clinical factors associated with ICU mortality and long-term survival in patients with CND who developed acute respiratory failure (ARF). METHODS: This retrospective cohort study was conducted in a level III respiratory ICU. Patients with pre-existing CND admitted to the ICU with ARF were included. ICU mortality was analyzed using multivariable logistic regression. Long-term survival after ICU discharge was evaluated using Kaplan-Meier survival analysis and Cox proportional hazards models. Mortality timing was further characterized using hazard function analysis. RESULTS: A total of 220 patients were included; the most common neurological diagnoses were dementia (37.3%), stroke (22.7%), and amyotrophic lateral sclerosis (14.1%). ICU mortality was 33.6%. Higher APACHE II scores were independently associated with increased ICU mortality (OR 1.076 per point increase; 95% CI 1.029-1.126; p < 0.001). Long-term survival differed significantly by post-discharge respiratory support strategy, with Kaplan-Meier analysis demonstrating more favorable survival patterns among patients receiving home non-invasive mechanical ventilation (NIMV) (p = 0.003). In Cox regression analysis, age, home NIMV, and feeding modality at discharge were independently associated with long-term outcomes. Survival analyses revealed an early clustering of deaths within the first months after ICU discharge, particularly among patients with dementia. CONCLUSIONS: In patients with CND, acute physiological severity was the main determinant of ICU mortality, whereas long-term survival after ICU discharge was poor, with deaths clustering within the first months thereafter. Post-discharge respiratory support and nutritional management should be individualized according to the expected clinical trajectory and patient values.

Humans↗

PubMed2026

Indications, Techniques and Complications Associated With Pterygoid Implants: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Pterygoid implants represent a graftless option for rehabilitation of patients with posterior maxillary atrophy, engaging the dense cortical bone of the pterygomaxillary complex. Despite clinical growth, a comprehensive synthesis of indications, surgical techniques, and complications is lacking. This review evaluated the prevalence of complications, implant survival rates, and marginal bone loss (MBL) associated with pterygoid implant placement. METHODS: The reporting of this review follows PRISMA 2020 guidelines. Six electronic databases (PubMed, Ovid, Scopus, WoS, CENTRAL, and Dentistry & Oral Sciences Source) were searched from 1 January 2020 to 31 December 2025. Included criteria comprised randomized and non-randomized clinical studies reporting outcomes of pterygoid implants (≥ 13 mm) in adult patients with posterior maxillary atrophy (minimum 10 implants). Risk of bias was assessed using JBI critical appraisal checklists. Proportions were pooled using the Freeman-Tukey double arcsine transformation under a random-effects model. Certainty of evidence was assessed using GRADE. RESULTS: Seventeen studies reporting 846 patients and 1915 pterygoid implants were included. The pooled survival rate was 97.9% (95% CI: 97.1%-98.6%; I2 = 0%; 14 studies) and the overall failure rate was 2.1% (95% CI: 1.4%-3.0%). Early failure rate was 0.9% (95% CI: 0.0%-3.0%; I2 = 59.5%). Late failure and MBL were summarized narratively. Certainty of evidence was low to very low. CONCLUSIONS: Pterygoid implants demonstrate excellent survival (97.9%) and low failure rates (2.1%), primarily early, supporting their reliability as a graftless solution for posterior maxillary atrophy. Complications appear infrequent though heterogeneously reported. Low evidence certainty necessitates prospective studies with standardized outcome reporting.

Humans↗

PubMed2026

Cardiovascular Drug Access in Australia and New Zealand: New PBS and PHARMAC Listings, 2023-2025.

BACKGROUND: Cardiovascular disease is a leading cause of death in Australia and New Zealand. Publicly subsidised access to new cardiovascular medications is governed by the PBS (Pharmaceutical Benefits Scheme) in Australia and PHARMAC (Pharmaceutical Management Agency) in New Zealand, yet no consolidated resource catalogues recent listings across both jurisdictions. METHODS: We reviewed all new cardiovascular drug listings and indications on the PBS and PHARMAC schedules from 1 January 2023 to 31 December 2025. PBS data were obtained from the PBS Pricing and Policy Branch through the Cardiac Society for Australia and New Zealand. PHARMAC data were obtained via direct communication with PHARMAC and cross-referenced with public schedule information. Pivotal trial evidence, restriction criteria, and prescribing considerations were extracted from published literature and regulatory documents. RESULTS: Five new cardiovascular drugs were PBS-listed (inclisiran, mavacamten, tafamidis, icosapent ethyl and migalastat), two existing drugs received new cardiovascular indications (empagliflozin and dapagliflozin for heart failure with preserved ejection fraction) and prasugrel was relisted for acute coronary syndrome. One major change occurred on the PHARMAC schedule (empagliflozin for heart failure with reduced ejection fraction). CONCLUSIONS: The 2023-2025 period has seen notable additions to cardiovascular pharmacotherapy in Australia, including the first cardiac myosin inhibitor, the first transthyretin stabiliser, expanded lipid lowering therapy options, and extension of SGLT2 inhibitor coverage across the heart failure ejection fraction spectrum. A pronounced access disparity persists between Australia and New Zealand.

New Zealand↗

PubMed2026

Cine-derived mitral annular relaxation velocity for detection of preclinical left ventricular diastolic dysfunction.

OBJECTIVES: Imaging diastolic dysfunction in pre-clinical heart failure (HF) is challenging. We evaluated a novel cardiac MRI (CMR) biomarker, CMR e-prime (CMR-MARV), in patients at risk of HF. METHODS: In this substudy of the PARABLE trial (NCT04687111), 236 patients (71.6 ± 7.7 years, 61.6% male) fulfilling trial-defined ALVDD citeria underwent CMR with measurement of mitral annular relaxation velocity (CMR-MARV) at four mitral annular anchor points. Diastolic strain rates from FT were also assessed. Twenty-five age- and sex-matched controls were included (73.8 ± 3.1 years, 52% male). Group differences were tested with t-tests, diagnostic accuracy with ROC analysis, and predictors of diastolic dysfunction with adjusted logistic regression. RESULTS: Compared with controls, patients had significantly higher indexed maximal left atrial volume (LAVimax), LV end-diastolic and end-systolic volumes, and LV mass (all p < 0.001). Of FT variables, only peak diastolic longitudinal velocity differed between groups (p < 0.001). In multivariate models, CMR-MARV correlated with radial, circumferential, and longitudinal diastolic strain rates, radial and longitudinal diastolic velocities (all p < 0.001), echocardiographic e' (r = 0.20, p = 0.007), LV mass (r = -0.18, p = 0.008), LAVimax (r = -0.18, p = 0.008), and NT-proBNP (r = -0.30, p < 0.0001). LAVimax and CMR-MARV were strongly independently associated with ALVDD (AUC 0.89 and 0.76, respectively; p < 0.0001). A combined model (LAVimax + CMR-MARV) achieved excellent discrimination (AUC 0.91, 95% CI 0.86-0.97, p < 0.0001). Independent predictors included LAVimax, CMR-MARV, and peak diastolic longitudinal velocity (all p < 0.001). CONCLUSION: CMR-MARV provides a simple cine-derived measure of longitudinal relaxation that correlates with established structural and biochemical markers of diastolic burden. Within an at-risk population, it offers incremental functional information beyond conventional parameters and may support multiparametric CMR phenotyping of preclinical diastolic dysfunction.

Aged↗

PubMed2026

Type, severity, frequency and management of adverse reactions associated with ultrasound contrast agents: a systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis are aimed at evaluating the incidence of adverse drug reactions (ADRs) following administration of clinically approved ultrasound contrast agents (UCAs) in adults and children, to assess risks in patients with cardiovascular disease and in pregnancy, and to evaluate the effectiveness of emergency management of severe ADRs. MATERIALS AND METHODS: A PRISMA 2020 systematic review was conducted searching PubMed, Scopus, and Embase. Two reviewers independently screened, extracted data, and assessed quality. Incidence estimates were pooled when feasible, stratified by age group, contrast agent, and administration route. RESULTS: Seventy-four studies encompassing > 1 million adults and > 36,000 children were included, contributing multiple analytic cohorts to the quantitative synthesis. Severe acute ADRs were extremely rare (6 and 16 cases per 100,000 in adults and children, respectively) and absent following endocavitary administration in children. Non-severe acute ADRs occurred in 11 and 8 cases per 10,000 adults and children, respectively. Delayed reactions were very rare (< 1 case per million in adults). No significant safety differences emerged between UCA products. The incidence of ADRs in patients with cardiovascular disease was analogous to the general population. No ADRs were reported in pregnant women. Standard emergency management was effective in almost all serious cases, though rare fatalities occurred. CONCLUSION: UCAs show an excellent safety profile in adults and children, with very rare severe ADRs and few non-severe, typically self-limiting reactions. Strict adherence to recommended emergency management protocols mitigates the remaining risks, supporting safe use across a broad range of clinical indications. PROSPERO REGISTRATION: CRD42023432668. KEY POINTS: Question What is the incidence, type, and severity of acute and delayed ADRs associated with clinically approved UCAs across different patient populations? Findings Severe acute adverse reactions are very rare, and non-severe reactions are rare and self-limiting, with no significant safety differences between adults, children, or patients with cardiovascular disease. Clinical relevant UCAs show an excellent safety profile across populations. These findings support their safe clinical use as reliable alternatives to iodine-based and gadolinium-based contrast agents in routine diagnostic imaging.

Contrast Media↗

PubMed2026

ORBIT: Oncogenic Representation Learning via Bi-Prototype Contrastive Learning in Hyperbolic Space for cancer driver gene identification.

Accurate identification of cancer driver genes is crucial for precision oncology but remains challenging due to the complexity of integrating heterogeneous data and modeling dynamic biological systems. To address these limitations, we propose ORBIT (Oncogenic Representation Learning via Bi-Prototype Contrastive Learning in Hyperbolic Space). Our framework synergistically fuses multi-omics profiles with functional network data using a context-adaptive graph reweighting mechanism to capture cancer-specific dynamics. The model employs a bi-prototype contrastive learning strategy within hyperbolic space, which aligns gene representations around distinct driver and non-driver semantic anchors while preserving the intrinsic hierarchy of biological networks. Comprehensive evaluations demonstrate that ORBIT achieves highly competitive stability in pan-cancer analysis while consistently outperforming state-of-the-art methods in cancer-specific predictions. Furthermore, functional enrichment analysis confirms that the model effectively segregates core cancer pathways, and drug sensitivity profiling validates the clinical relevance of the identified drivers. By integrating hyperbolic geometry with context-adaptive learning, ORBIT offers a robust and interpretable paradigm for precision medicine. The source codes and datasets are publicly accessible at https://github.com/spcho-dev/ORBIT.

Humans↗

PubMed2026

Outcomes of Suture Tape-Augmented ACL Reconstruction in Patients With High Internal Rotational Tibial Subluxation: A Minimum 3-Year Cohort Study.

BACKGROUND: Anterior cruciate ligament reconstruction (ACLR) using hamstring tendon (HT) autografts faces persistent challenges of graft failure, especially in patients with high internal rotational tibial subluxation (IRTS). HYPOTHESIS: Patients with high IRTS who undergo HT autograft ACLR with suture tape augmentation (STA) will have lower graft failure rates and superior clinical outcomes as compared with those without STA. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This retrospective cohort study included patients with high IRTS-defined as lateral minus medial anterior tibial subluxation >5.8 mm based on prior studies-who underwent primary ACLR using HT autografts with STA and had a minimum follow-up of 3 years. Propensity score matching (1:1) was performed to identify a control group of patients with similarly high IRTS who underwent HT ACLR without STA. Postoperative outcomes were assessed by the International Knee Documentation Committee score, Lysholm score, and Tegner activity scale, as well as by return-to-sport status and graft failure. Clinically meaningful improvements were evaluated by the minimal clinically important difference, Patient Acceptable Symptom State, and substantial clinical benefit. RESULTS: This study included 62 patients with high IRTS: 31 with STA and 31 matched controls. The mean IRTS was 6.6 mm (range, 5.9-8.9) in the STA group and 6.8 mm (range, 5.8-8.7) in the control group. The mean patient age was 32.9 years (range, 20-50), and the mean follow-up was 3.8 years (range, 3.1-5.0). At final follow-up, the STA group showed significantly higher proportions of patients achieving the minimal clinically important difference (93.5% vs 74.2%; P = .038), Patient Acceptable Symptom State (96.8% vs 74.2%; P = .012), and substantial clinical benefit (54.8% vs 25.8%; P = .020). The return-to-sport rate was also higher in the STA group (74.2% vs 48.4%; P = .037). Additionally, the STA group demonstrated a lower graft failure rate (0% vs 12.9%; P = .039). CONCLUSION: For patients with high IRTS, STA in ACLR with HT autografts is associated with improved clinical outcomes, a higher return-to-sport rate, and a lower risk of graft failure at midterm follow-up.

Humans↗