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Ultrashort vs Standard-Duration Dual Antiplatelet Therapy in Acute Coronary Syndrome Patients Undergoing PCI: A Meta-Analysis.

BACKGROUND: The efficacy and safety of ultrashort (&#x2264;1-month) dual antiplatelet therapy (DAPT) followed by antiplatelet monotherapy remain uncertain in acute coronary syndrome (ACS) patients. OBJECTIVES: This study sought to compare ultrashort vs standard-duration DAPT in patients with ACS undergoing percutaneous coronary intervention (PCI). METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials until February 15, 2026. Primary outcomes were major adverse cardiac and cerebrovascular events (MACCE), major bleeding, and net adverse clinical event (NACE). Prespecified subgroup analyses examined by ethnicity (East Asian vs non-East Asian) and abbreviation strategy (intensive: &#x2264;1-week DAPT or clopidogrel/aspirin monotherapy vs moderate: &#x2265;2-week DAPT, followed by ticagrelor/prasugrel monotherapy). RESULTS: Across 10 trials (n = 29,232), ultrashort DAPT did not increase MACCE risk (HR: 1.06; 95% CI: 0.93-1.20; P = 0.38; I2 = 24%), with higher MACCE risk observed in ST-segment elevation myocardial infarction (STEMI) but not non-ST-segment elevation ACS (NSTE-ACS), and significantly reduced major bleeding (HR: 0.47; 95% CI: 0.35-0.64; P < 0.00001; I2 = 44%), resulting in a net clinical benefit (HR: 0.83; 95% CI: 0.72-0.97; P = 0.02; I2 = 61%). Bleeding reduction was more pronounced in East Asians (HR: 0.35; 95% CI: 0.25-0.49; P < 0.00001; I2 = 0%) than non-East Asians (HR: 0.63; 95% CI: 0.43-0.93; P = 0.02; I2 = 44%), with a significant interaction (P = 0.02). The abbreviation strategy significantly modified outcomes (P for interaction = 0.003): intensive abbreviation raised MACCE risk (HR: 1.37; 95% CI: 1.11-1.69; P = 0.003; I2 = 0%), while moderate abbreviation had no statistically significant difference (HR: 0.96; 95% CI: 0.85-1.08; P = 0.47; I2 = 0%). CONCLUSIONS: In patients with ACS undergoing PCI, ultrashort DAPT reduced bleeding without increasing ischemic events overall, although a signal of increased MACCE was observed in STEMI but not in NSTE-ACS. Bleeding reduction was greater in East Asians, while &#x2264;1-week DAPT or clopidogrel/aspirin monotherapy may increase ischemic risk.

Humans

Interventions with a significant mortality difference in acute respiratory distress syndrome: A systematic review and comparison with Guidelines.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) has a high mortality rate. European Society of Intensive Care Medicine (ESICM) and American Thoracic Society (ATS) Guidelines are the worldwide reference for clinicians in management of ARDS. Mortality represents one of the most important outcomes in intensive care practice and randomized controlled trials (RCTs) the highest level of evidence. We compared Guidelines recommendations with RCT results to highlight differences and find potential new therapeutic opportunities. METHODS: We performed a systematic review of all RCTs reporting a statistically significant mortality difference in ARDS and a subsequent comparison with ESICM and ATS Guidelines recommendations. RESULTS: We identified 33 RCTs and 23 interventions with mortality difference in ARDS patients. Seven interventions relate to invasive ventilation strategies, two to noninvasive ventilation strategies, one to extracorporeal membrane oxygenation (ECMO), 12 to drugs and one to nutritional support. In 25/33 (76%) RCTs the intervention was associated with mortality reduction and in 8/33 with mortality increase (24%). Multicenter studies were 24/33 (73%) while blinding was adopted in 19/33 (58%) studies. Guidelines recommendations supported by RCTs with mortality impact include: the use of low tidal volume ventilation, prone positioning, venovenous ECMO, steroids and the avoidance of high frequency oscillatory ventilation. Eight of the interventions identified were not mentioned by Guidelines but demonstrated reduced mortality, and five further interventions demonstrated increased mortality. CONCLUSIONS: This systematic review highlights potential gaps between RCTs results and Guidelines that could be used to plan future research or highlight topics to be discussed in future Guidelines.

Humans

Efficacy and safety of human albumin combined with furosemide in acute decompensated heart failure with hepatic dysfunction.

BACKGROUND: Congestion is the most common clinical presentation on admission of patients with acute decompensated heart failure (ADHF). Finding effective ways to alleviate congestion has become a pivotal management step. This study sought to investigate the efficacy and safety of intravenous (IV) albumin use in conjunction with furosemide in patients hospitalized for ADHF with hepatic dysfunction in terms of subjective regression of congestion symptoms and worsening renal function. METHODS: This prospective, open-label, randomized-pragmatic trial recruited 241 patients with hepatic dysfunction hospitalized for ADHF. Patients (78 years, 54% female) were assigned to receive IV albumin with furosemide or IV furosemide alone. The coprimary study endpoints were patients' global assessment of symptoms score, quantified as the area under the curve (AUC) of the score on a visual analog scale, and the change in creatinine levels over 72 hours from admission. RESULTS: The experimental treatment group demonstrated a greater improvement in patients' global assessment of symptoms scores (AUCbaseline-72 h 3,767 vs 3,457 points; P < .001) and a milder increase in creatinine levels (0.07 vs 0.18 mg/dL; P = .045) than the IV furosemide group. The length of stay was 1 day shorter (4 vs 5 days; P < .001) and the incidence of worsening renal function was lower (25% vs 38%; P = .037) in the experimental treatment group. CONCLUSIONS: In this hypothesis generating study, among patients with ADHF and hepatic dysfunction, concomitant use of IV albumin and furosemide for the first 72 hours resulted in a significant improvement in subjective perception symptoms of decongestion and a milder increase in creatinine levels than IV furosemide alone.

Aged

[Effect of oblique needling after equal division and positioning of anatomic points on acute sacroiliac joint injury assessed with infrared thermography].

OBJECTIVE: To evaluate the clinical therapeutic effect of oblique needling after equal division and positioning of anatomic points on acute sacroiliac joint injury assessed with infrared thermography. METHODS: A total of 150 patients with acute sacroiliac joint injury were randomly divided into an oblique needling group, a perpendicular needling group, and an acupressure+tuina group, with 50 cases in each group. After equal division and positioning of anatomic points at sacroiliac joints, the oblique needling, perpendicular needling and acupressure+tuina techniques of acupuncture were operated in three groups, respectively. The treatment was administered once daily, 5 sessions per week; 10 sessions constituted one treatment course, with a total of one course required in the trial. Before and after treatment, the scores of Japanese Orthopaedic Association (JOA), visual analogue scale (VAS) of pain, and World Health Organization quality of life-BREF (WHO QOL-BREF), as well as the average temperature of the lumbosacral region were observed in each group. Additionally, the correlation between the average lumbosacral temperature and efficacy indicators was explored. RESULTS: After treatment, the scores of JOA, WHO QOL-BREF in the oblique needling group were higher (P<0.01, P<0.001), and the VAS score was lower (P<0.01, P<0.001) than those in the perpendicular needling group and the acupressure+tuina group; and the average temperature of the affected lumbosacral region in the oblique needling group was lower compared with that in the other two groups (P<0.001). After treatment, the average lumbosacral temperature of the affected side showed a negative correlation with the JOA score in each group (r=-0.645, -0.482, -0.809, P<0.001). CONCLUSION: Following equal division and positioning of anatomic points, the therapeutic effect of acupuncture with oblique needling is superior to the perpendicular needling and acupressure+tuina on acute sacroiliac joint injury. The average temperature of the affected lumbosacral region is correlated with the severity of lumbosacral dysfunction after treatment.

Humans

Spironolactone, early acute eGFR changes, and clinical outcomes in patients with heart failure with preserved ejection fraction: insights from TOPCAT Americas.

AIMS: Early acute changes in estimated glomerular filtration rate (eGFR) have been well described with renin-angiotensin system inhibitors and sodium-glucose cotransporter-2 inhibitors, but less is known about the frequency, prognostic relevance, and implications of these changes after mineralocorticoid receptor antagonist (MRA) initiation in patients with heart failure with preserved ejection fraction (HFpEF). METHODS: We performed a post-hoc analysis of 1648 patients enrolled in the TOPCAT trial (Americas regional subgroup), defining an early eGFR dip as a &#x2265;15% decrease in eGFR between baseline and week 4. Landmark analyses assessed the association of eGFR changes, treatment, and the primary composite endpoint (cardiovascular death, HF hospitalization, or aborted cardiac arrest). RESULTS: Within 4 weeks of treatment initiation, 431 (26%) patients experienced acute eGFR decrease with a higher proportion of patients assigned to spironolactone [269 (33%)] compared with placebo [162 (20%)] (odds ratio 1.97; 95% confidence interval 1.58-2.47). An acute eGFR decrease was independently associated with higher risk of subsequent cardiovascular outcomes, irrespective of treatment arm. However, treatment with spironolactone appeared beneficial in reducing the primary cardiovascular outcome irrespective of the presence [hazard ratio 0.75 (0.53-1.08)] or absence [0.80 (0.64-1.00)] of early eGFR decrease (Pinteraction = .81). At any given magnitude of eGFR decline, risk of the primary endpoint was consistently lower with spironolactone compared with placebo (Pinteraction = .64). CONCLUSIONS: Early acute eGFR changes were common and adversely prognostic in patients with HFpEF. Spironolactone treatment was beneficial in improving cardiovascular outcomes, despite a modest increase in the likelihood of acute eGFR decrease. An acute eGFR decrease early after MRA initiation should not automatically prompt treatment discontinuation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00094302.

Humans

Randomised, Multicentre Clinical Trial Found That Hypertonic Saline Did Not Reduce the Length of Stay of Hospitalised Patients With Acute Bronchiolitis.

AIM: Bronchiolitis is a major cause of hospitalisation in young children, but the effectiveness of inhaled hypertonic saline remains unclear. We compared treating hospitalised infants with nebulised hypertonic saline or normal saline. METHOD: This multisite, double-blind RCT was conducted from 1 October 2023 to 1 April 2025 in four Polish paediatric units. Children from 5&#x2009;weeks to 24&#x2009;months, who had been hospitalised with mild-to-moderate bronchiolitis, were randomly assigned to receive nebulised 3% hypertonic saline or 0.9% normal saline until discharge. They were followed for 7&#x2009;days. RESULTS: The study comprised 181 children (55% male) with a mean age of 8.3&#x2009;&#xb1;&#x2009;6.3&#x2009;months: 90 were randomised to hypertonic saline and 91 to normal saline. The median hospital stay was 2.68 (1.92-4.03) days in the hypertonic saline group and 2.79 (1.8-3.96) days in the normal saline group. The mean difference was -0.11&#x2009;days (95% confidence interval -0.73 to 0.12, p&#x2009;=&#x2009;0.3). No differences were observed in clinical severity scores between the groups. Readmissions only occurred in the normal saline group (5.9%). CONCLUSION: Hypertonic saline inhalation did not reduce the length of hospital stay or improve clinical severity scores in hospitalised children with bronchiolitis, but it was associated with a lower risk of rehospitalisation.

Humans

Acute Stevia Consumption does not Alter Endocrine Responses in Individuals with Normal Weight, Overweight, and Type 2 Diabetes Mellitus.

BACKGROUND: Stevia is a plant-based non-nutritive sweetener. Acute effects of stevia ingestion on glycemia and hormonal responses have not been fully investigated. OBJECTIVE: This objective of this study was to evaluate the acute effects of beverages containing stevia alone and in combination with glucose on glycemic, hormonal, and appetite responses. METHODS: This study evaluated three cohorts of n=23 individuals with either normal weight (NW), overweight (OW), or type 2 diabetes mellitus (T2DM) for which each individual completed four test conditions in a randomized sequence crossover study design. The four test conditions were beverages containing stevia (75.6 mg steviol equivalents), water, glucose (30 g), and stevia+glucose (30 g glucose+75.6 mg steviol equivalents). Blood samples were collected before and for 180 min after beverage consumption. Assessments included net area under the curve (niAUC) and incremental maximal concentration values for plasma glucose, insulin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1, glucagon, and PYY. Appetite was assessed with visual-analog scale questions and energy consumption during an ad libitum meal. RESULTS: Responses to the stevia beverage did not differ significantly from those for water alone, and stevia + glucose did not differ significantly from glucose alone for any of the three groups. CONCLUSION: Acute stevia consumption did not materially alter responses for glycemia or hormones involved in glucose and appetite regulation, appetite ratings, or energy intake at a subsequent meal. Clinical Trial Registry number and website where it was obtained: Clinical Trials.gov Identifier: NCT05287906. Study Details | NCT05287906 | A Trial to Assess Steviol Glycosides on Acute Appetite Hormone Release | ClinicalTrials.gov.

Appetite

Efficacy of sodium-glucose cotransporter 2 inhibitors after acute myocardial infarction: Are the benefits limited to patients with diabetes? A systematic review and meta-analysis.

BACKGROUND: Acute myocardial infarction remains one of the leading causes of death worldwide. Recently, studies have focused on evaluating the effectiveness of SGLT2 inhibitors in this scenario. Objectives We aimed to perform a meta-analysis comparing the efficacy of SGLT2 inhibitors vs standard care. METHODS: We systematically searched PubMed, Embase, and Cochrane for randomized controlled trials (RCTs) and observational studies comparing patients with acute myocardial infarction using iSGLT2 inhibitors and standard care. Statistical analyses were conducted using R software (v 4.3.2) and a random-effects model was employed for all outcomes. RESULTS: A total of 31,378 patients were included, with 10,897 (34.7%) assigned to the SGLT2 inhibitor group. Among these studies, three were randomized controlled trials (RCTs). There was a significant difference in reduction of HF readmissions (OR 0.61; p&#xa0;<&#xa0;0.01), all-cause mortality (OR 0.62; p&#xa0;<&#xa0;0.01;) and stroke (OR 0.67; p&#xa0;<&#xa0;0.01;). However, there was no significant difference in cardiovascular death, rehospitalization for any cause and recurrence of acute MI. Meta regression and subgroup analysis showed a trend toward better outcomes in the diabetic and non-STEMI population. CONCLUSIONS: SGLT2 inhibitors were associated with lower HF rehospitalization, stroke, and all-cause mortality after acute MI, mainly in observational studies. Benefits appeared greater in diabetic and non-STEMI patients. Dedicated RCTs focusing on diabetic, particularly non-STEMI, populations are needed to confirm these findings. KEY POINTS: What is already known on this topic: SGLT2 inhibitors have demonstrated cardiovascular and renal benefits in patients with heart failure and type 2 diabetes mellitus. However, their role in the acute myocardial infarction (AMI) setting remains uncertain, particularly regarding post-AMI outcomes such as heart failure readmissions, mortality, and recurrent ischemic events, with current evidence derived from heterogeneous and predominantly observational studies. WHAT THIS STUDY ADDS: This meta-analysis, including over 31,000 patients, suggests that SGLT2 inhibitors are associated with reductions in heart failure readmissions, all-cause mortality, and stroke following AMI. These associations were more consistently observed in patients with type 2 diabetes and in non-ST-segment elevation myocardial infarction (NSTEMI) populations. However, randomized controlled trials showed neutral results, and the observed benefits were mainly driven by observational studies. Meaning: These findings should be interpreted as hypothesis-generating. While SGLT2 inhibitors may represent a potential therapeutic strategy in selected post-AMI populations, particularly patients with diabetes and NSTEMI, current evidence does not support routine early in-hospital initiation. Dedicated randomized trials specifically enrolling diabetic post-AMI patients are required to clarify optimal timing and clinical benefit.

Humans

Integrated bioinformatics analysis reveals cross-talking hub genes and therapeutic agents between sepsis and acute myocardial infarction.

BACKGROUND: Sepsis and acute myocardial infarction (AMI) are two significant diseases that may share overlapping etiological mechanisms. This study aims to systematically identify core genes common to both conditions and to explore their potential as therapeutic targets and drug candidates through an integrative analysis of clinical data and bioinformatics. METHODS: The AMI dataset was obtained from the GEO database, and RNA sequencing data were collected from blood samples of patients with sepsis at our hospital. Common genes were identified using differential expression gene analysis (DEG) and weighted gene co-expression network analysis (WGCNA). Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were performed. A protein-protein interaction (PPI) network was constructed, and hub genes were identified using the MCC/Degree algorithm. Diagnostic value was assessed via receiver operating characteristic curve analysis. Immune infiltration patterns, single-cell sequencing data, and molecular docking simulations were employed to evaluate immune relevance and identify potential therapeutic compounds. RESULTS: A total of 417 genes were identified between sepsis and AMI, with enrichment analysis revealing significant involvement in inflammatory responses. Three hub genes-JAK2, MYD88, and TIMP1-were selected for further investigation. ROC curves confirmed their strong diagnostic performance for both diseases. Immune infiltration analysis showed that these core genes were significantly correlated with the infiltration levels of various immune cell types. Molecular docking indicated that quercetin exhibited stable binding affinity with the proteins encoded by these genes. qPCR validation further confirmed the upregulation of these three genes, supporting the anti-inflammatory effects of quercetin as a potential targeted therapy. CONCLUSION: JAK2, MYD88, and TIMP1 were identified as shared core genes in sepsis and AMI. These genes not only serve as potential diagnostic biomarkers but also offer novel targets for developing common therapeutic strategies for both conditions. Furthermore, quercetin emerges as a promising candidate for targeted treatment.

Humans

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 &#x2265;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 &#x2265;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 &#x2265;40%. These findings are hypothesis-generating and require external validation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05164653; Japan Registry of Clinical Trials, jRCTs021210046.

Humans

Ibuprofen versus acetaminophen for acute mild-to-moderate pain management in pediatric populations: a systematic review and meta-analysis of their efficacy.

UNLABELLED: Ibuprofen and acetaminophen are the most widely used analgesics in pediatric practice for the management of acute mild-to-moderate pain. Despite their widespread use, the comparative analgesic efficacy of these two agents in children remains a subject of ongoing debate, with existing evidence largely derived from heterogeneous clinical settings and small individual trials. Therefore, this study aimed to systematically review and meta-analyze randomized controlled trials comparing the analgesic efficacy of ibuprofen versus acetaminophen in pediatric populations with acute mild-to-moderate pain. A systematic literature search was conducted up to May 2026 in PubMed, Scopus, and Web of Science. The review was conducted and reported in accordance with the PRISMA-Children and Adolescents (PRISMA-C) 2026 reporting guideline. Eligible studies were randomized controlled trials comparing ibuprofen with acetaminophen in children and adolescents (defined as individuals aged 0 to&#x2009;<&#x2009;18&#xa0;years) with acute pain, reporting at least one extractable efficacy outcome. Continuous outcomes were synthesized as standardized mean differences (Hedges' g) using random-effects models; dichotomous outcomes were pooled as risk ratios (RRs) with 95% confidence intervals. Risk of bias was assessed using the Cochrane RoB 2 tool and certainty of evidence was evaluated using the GRADE framework. Eight randomized controlled trials enrolling 1325 participants were included. Three pediatric trials contributed to the primary continuous pain outcome meta-analysis (n&#x2009;=&#x2009;196 analyzable participants), yielding a pooled SMD of&#x2009;-&#x2009;0.28 (95% CI&#x2009;-&#x2009;0.57 to 0.00; p&#x2009;=&#x2009;0.052; I2&#x2009;=&#x2009;0%), indicating a small effect favoring ibuprofen that did not reach conventional statistical significance. Given the small number of contributing studies (k&#x2009;=&#x2009;3), the I2 statistic should be interpreted with caution as it has limited power to detect heterogeneity in this context. For the dichotomous pain freedom outcome (2 trials, n&#x2009;=&#x2009;114), no significant difference was observed (pooled RR 1.03, 95% CI 0.53-1.99; p&#x2009;=&#x2009;0.93; I2&#x2009;=&#x2009;0%). A prespecified sensitivity analysis including an adult soft-tissue injury trial attenuated the pooled effect toward the null (SMD&#x2009;-&#x2009;0.15, 95% CI&#x2009;-&#x2009;0.38 to 0.09; p&#x2009;=&#x2009;0.23; I2&#x2009;=&#x2009;36.6%). Narrative synthesis of additional studies generally demonstrated comparable analgesic efficacy between the two agents across postoperative and outpatient pediatric settings. The overall certainty of evidence was rated as low for both primary outcomes, primarily due to imprecision and indirectness. CONCLUSION: Current evidence from randomized controlled trials does not demonstrate a superiority of ibuprofen over acetaminophen for acute mild-to-moderate pain management in children. Both agents appear to provide clinically meaningful analgesia across heterogeneous pediatric pain settings. The clinical choice between agents should be guided by individual patient factors, including contraindications to NSAIDs, the inflammatory nature of the pain etiology, and patient-specific characteristics. The low certainty of evidence underscores the need for adequately powered, methodologically rigorous trials to definitively establish the comparative efficacy of these two analgesics in the pediatric population. WHAT IS KNOWN: &#x2022; Ibuprofen and acetaminophen are the two most widely used non-opioid analgesics for acute mild-to-moderate pain in children, and both are recommended as first-line agents by major international guidelines. &#x2022; Prior meta-analyses in mixed pediatric-adult populations have suggested a modest analgesic advantage of ibuprofen over acetaminophen, but pediatric-specific evidence has remained limited and methodologically heterogeneous. WHAT IS NEW: &#x2022; This systematic review and meta-analysis, restricted to randomized controlled trials in pediatric populations, found that ibuprofen showed a small effect favoring pain reduction compared with acetaminophen (SMD&#x2009;-&#x2009;0.28, p&#x2009;=&#x2009;0.052), although this did not reach conventional statistical significance. &#x2022; The analgesic advantage of ibuprofen may be more pronounced in pain etiologies with a significant inflammatory component (e.g., fractures). At the same time, both agents appear broadly equivalent in most other acute pediatric pain settings, supporting individualized analgesic selection based on clinical context and patient-specific factors.

Humans

Teaching Acute Coronary Syndrome High-Risk ECG Interpretation and Clinical Decision-Making Through FOAMed Videos and Podcast Versus Print-Based Materials Among Emergency Care Providers: Randomized Controlled Mixed Methods Trial.

BACKGROUND: Accurate interpretation of high-risk acute coronary syndrome (ACS) electrocardiograms (ECGs) is essential for early diagnosis and timely reperfusion, yet substantial deficits persist across health care professions. Digital self-learning formats such as FOAMed (Free Open Access Medical Education) are widely used, but their effectiveness has rarely been evaluated for complex, high-risk ACS ECG patterns. Existing ECG education studies often focus on students or single professional groups and established ST-segment elevation myocardial infarction (STEMI) criteria, leaving newer guideline-recognized STEMI equivalents, selected emerging occlusion myocardial infarction (OMI)-related patterns, and interprofessional emergency care underrepresented. OBJECTIVE: This study aimed to compare the effectiveness of FOAMed podcast and videos versus traditional print-based materials for teaching high-risk ACS ECG patterns and related clinical decision-making in emergency providers. METHODS: We conducted a prospective, interprofessional, controlled mixed methods trial across 5 training sites in Germany. Paramedics, prehospital emergency physicians, and emergency department clinicians received either a FOAMed multimedia module or print-based materials through concealed allocation; deviations from the intended 1:1 ratio resulted from participant no-shows. The intervention consisted of a 30-minute supervised self-learning session. In total, 103 participants were allocated to FOAMed (n=45) or print-based materials (n=58). Two coprimary outcomes were assessed: ECG interpretation accuracy and text-based ACS clinical decision-making. Secondary outcomes included subjective confidence, learning experience, and exploratory qualitative free-text responses. Outcome assessment was automated and blinded; mixed ANOVA was the primary analysis. The study was not prospectively registered because it assessed educational outcomes in health care professionals rather than patient health outcomes. RESULTS: All 103 participants completed the study. Both groups improved, with greater gains in the FOAMed group: ECG interpretation increased from 55% to 65.5% and text-based ACS clinical decision-making from 45% to 68%, versus 57% to 60% and from 47% to 63%, respectively, in the print-based group. Effect sizes were &#x3b7;&#xb2;=0.055 for ECG interpretation and &#x3b7;&#xb2;=0.044 for clinical decision-making. Exploratory subgroup analyses provided no evidence of differential effects across age, gender, or professional background and were likely underpowered. Qualitative responses (46 and 37 entries) provided contextual insights into perceived clarity, engagement, and practical relevance supporting the quantitative findings. CONCLUSIONS: This study is innovative in directly comparing a curated FOAMed multimedia module with selected print-based materials in an interprofessional emergency care population. It differs from existing research by focusing on subtle, emerging ischemic patterns and evaluating realistic, time-limited self-learning formats. The findings provide evidence that curated FOAMed resources can produce greater short-term improvements in ECG interpretation and text-based ACS clinical decision-making than traditional print-based materials in this setting. Although implications for clinical performance remain hypothetical, concise, high-quality digital modules may represent a practical supplement to structured continuing education in emergency care.

Humans

A combined stimulus of acute fasting and exercise modulates hippocampal mitochondrial quality control in healthy mice.

BACKGROUND AND AIMS: Exercise and fasting are recognized for their ability to improve brain health and mitigate neurodegeneration. However, little is known about how these interventions acutely impact mitochondrial quality control mechanisms including mitophagy. METHODS: We examined the effects of a single bout of fasting and exercise (FEx) on hippocampal mitochondrial function and proteomic remodeling in male and female mice. To assess in vivo autophagy dynamics, we combined proteomics with chloroquine (CQ) inhibition of autophagic flux. Mice were assigned to sedentary (Sed), fasting (F), exercise (Ex), or combined FEx groups and received unilateral intrahippocampal injections of CQ or PBS following treatments. Four hours later, hippocampi were collected for analysis. RESULTS: LC3-II levels significantly increased in the FEx group only following CQ treatment, indicating enhanced autophagic flux. Proteomic profiling showed sedentary males failed to mount a robust response to FEx however females exhibited upregulation of proteins involved in the TCA cycle, glutathione metabolism, and oxidative phosphorylation, suggesting greater mitochondrial adaptability. Functional assays supported these findings, females showed increased complex IV activity post-FEx. The mitochondrial DNA / nuclear DNA ratio increased after FEx regardless of sex, and upstream regulator analysis predicted activation of mitochondrial biogenesis. CONCLUSIONS: Together, these data reveal sex-specific mitochondrial remodeling in response to acute fasting and exercise. Defining these normative responses is critical for understanding how mitochondrial adaptability shapes resilience or vulnerability to neurological challenges.

Animals

The Acute Effects of Blood Flow Restriction on Ankle Muscle Reaction Time and Proprioception in Healthy Individuals.

Blood flow restriction (BFR) induces hypoxic and metabolic stress, which may alter afferent feedback and neuromuscular control. However, its acute effects on ankle sensorimotor function remain unclear. The aim of the study was to investigate the acute effects of lower-limb BFR on multidimensional ankle sensorimotor function in healthy adults. Twenty-four participants (12 females, 12 males) completed two conditions in randomized order and a crossover design: BFR at 60% arterial occlusion pressure (AOP) and a control condition (20 mmHg). All measurements were performed during occlusion. Outcomes included joint position sense (active and passive), kinesthesia, static and dynamic balance, lower-limb muscle activation (surface electromyography), and muscle reaction time during sudden ankle inversion. BFR impaired active joint position sense at 20 degrees of inversion (p = 0.011), with no changes at other angles or in kinesthesia. Static balance deteriorated, with increases in sway area (p = 0.017), sway distance (p = 0.029), and sway velocity (p < 0.001), particularly under eyes-closed single-leg stance. Posterolateral reach distance decreased (p = 0.023), accompanied by reduced lower-limb muscle activation. Tibialis anterior muscle reaction time during 30 degrees of inversion in the ankle neutral position was shortened (p < 0.001), whereas peroneus longus muscle responses were unchanged. Acute lower-limb BFR impairs ankle sensorimotor control by reducing proprioceptive accuracy, balance performance, and muscle activation, while shortening reaction time. These findings suggest caution when applying BFR during tasks that require high postural demands or end-range control. Registration number and date: NCT07307339, 12/26/2025.

Humans

Effects of acute resistance exercise on prefrontal oxygenation and task-switching performance: Considerations of loading strategies and blood flow restriction.

Although acute resistance exercise (RE) has been proposed to influence cognitive flexibility and underlying neural mechanisms, it remains unclear whether these effects vary across loading strategies and whether exercise-induced prefrontal hemodynamic responses translate into cognitive outcomes. The present study examined (1) prefrontal cortex (PFC) oxygenated hemoglobin (O2Hb) responses across exercise sets and conditions, (2) the effects of low-load (LL), LL with blood flow restriction (BFR), and high-load (HL) RE on task-switching performance, and (3) whether exercise-related PFC O2Hb responses were associated with pre- to post-exercise changes in task-switching performance. Thirty physically active adults completed three randomized, counterbalanced RE conditions consisting of four sets of barbell squats. LL was performed at 30% one-repetition maximum (1RM) with and without BFR, whereas HL was performed at 70% 1RM. Cognitive flexibility was assessed pre- and post-exercise using a modified Stroop task, indexed by switch-cost reaction time (RT) and accuracy. PFC O2Hb was assessed using functional near-infrared spectroscopy during exercise and expressed as changes from the resting baseline for each set (Sets 1-4). PFC O2Hb increased across sets, rising from Set 1 to Set 3 before plateauing, with no differences observed across conditions. Switch cost RT and accuracy did not improve from pre- to post-exercise, and no differences across conditions were detected. PFC O2Hb during the final set was not associated with changes in switch cost. These findings suggest that although acute RE elicits robust increases in prefrontal hemodynamic activity, such responses may not translate into acute improvements in cognitive flexibility.

Humans

Acute and chronic effects of mixed nuts on energy metabolism in women at cardiometabolic risk: a randomized clinical trial.

BACKGROUND AND AIMS: The effect of consuming a mix of Brazilian nuts on energy metabolism has not been explored. Thus, the present study aimed to evaluate the effects of acute and chronic consumption of mixed nuts on markers of energy metabolism in women with overweight/obesity. METHODS AND RESULTS: This is a randomized, controlled, and parallel clinical trial with adult women. In an acute study, participants received a beverage containing mixed nuts (30&#xa0;g of cashew nuts&#xa0;+&#xa0;15&#xa0;g of Brazil nuts) or a control beverage, and energy metabolism markers were assessed for up to 3&#xa0;h postprandially. For the chronic study, participants received 45&#xa0;g of a mix of nuts/day and a -500kcal energy-restricted diet (MNG) or only a -500kcal energy-restricted diet free of nuts (CTG) for 8 weeks, and energy metabolism was assessed before and after the intervention period. In the postprandial period, fat oxidation was higher in the MNG than in the CTG (piAUC: 47.53&#xa0;&#xb1;&#xa0;5.78&#xa0;mg/min vs. 27.93&#xa0;&#xb1;&#xa0;6.98&#xa0;mg/min; p&#xa0;=&#xa0;0.048). After 8 weeks of the intervention, fasting fat oxidation increased in the MNG (+16.0&#xa0;&#xb1;&#xa0;7.0&#xa0;mg/min) and decreased in the CTG (-5.0&#xa0;&#xb1;&#xa0;6.0&#xa0;mg/min), with no significant difference between groups. Other acute and chronic markers also showed no significant changes between groups. CONCLUSION: The acute consumption of mixed nuts increased postprandial fat oxidation, whereas chronic intake within an energy-restricted diet did not affect energy metabolism markers in women at cardiometabolic risk. REGISTRATION NUMBER FOR BRAZILIAN REGISTRY OF CLINICAL TRIALS: RBR-3ntxrm.

Humans

Efficacy, acceptability, and related outcomes of pharmacological interventions for acute bipolar mania: a systematic review and dose-related network meta-analysis across different age groups.

BACKGROUND: Acute bipolar mania carries negative social and economic consequences. We investigated the comparative efficacy/response/acceptability of pharmacological interventions for acute bipolar mania, considering dose effects across different age groups. METHODS: We conducted a network meta-analysis (NMA) to search for randomized controlled trials (RCTs) comparing pharmacological interventions with one another or placebo in acute bipolar mania patients, indexed in PubMed/MEDLINE, Embase, Web of Science, and Scopus (from inception through 2025.12.24). Co-primary outcomes were change in manic symptoms/response/and acceptability. Tolerability/remission and rate of adverse events were secondary outcomes. Confidence-In-Network-Meta-Analysis was likewise appraised. RESULTS: 113 RCTs, encompassing 49 distinct treatment combinations, included 20,666 participants. Sensitivity analysis retaining only low-risk-of-bias studies and excluding outliers for possible effect modifiers indicated that risperidone 3&#xa0;mg/day(SMD&#xa0;=&#xa0;-7.57;95%C.I.&#xa0;=&#xa0;-8.25;-5.85); tamoxifen 160&#xa0;mg/day(SMD&#xa0;=&#xa0;-1.73;95%C.I.&#xa0;=&#xa0;-2.32;-1.13); rivastigmine 3&#xa0;mg/day(SMD&#xa0;=&#xa0;-1.13;95%C.I.&#xa0;=&#xa0;-1.06;-0.58); haloperidol 30&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.96;95%C.I.&#xa0;=&#xa0;-1.25;-0.75); valproate 750&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.76;95%C.I.&#xa0;=&#xa0;-1.48;-0.58); tamoxifen 40&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.75;95%C.I.&#xa0;=&#xa0;-1.41;-0.59); celecoxib 400&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.74;95%C.I.&#xa0;=&#xa0;-1.20;-0.38); paliperidone extended-release 12&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.62; 95%C.I.&#xa0;=&#xa0;-0.91;-0.32); olanzapine 15&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.59;95%C.I.&#xa0;=&#xa0;-0.60;-0.38); olanzapine 20&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.52;95%C.I.&#xa0;=&#xa0;-0.66;-0.38); risperidone 4&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.53;95%C.I.&#xa0;=&#xa0;-0.76;-0.29); allopurinol 600&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.54;95%C.I.&#xa0;=&#xa0;-0.67;-0.22); cariprazine 12&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.49;95%C.I.&#xa0;=&#xa0;-0.66;-0.33); risperidone 4.2&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.46;95%C.I.&#xa0;=&#xa0;-0.75;-0.17); lithium 1500&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.42;95%C.I.&#xa0;=&#xa0;-0.57;-0.28); ziprasidone 160&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.49;95%C.I.&#xa0;=&#xa0;-0.68;-0.31); asenapine 20&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.38;95%C.I.&#xa0;=&#xa0;-0.53;-0.22); haloperidol 8&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.34;95%C.I.&#xa0;=&#xa0;-0.63;-0.05); aripiprazole 15&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.33;95%C.I.&#xa0;=&#xa0;-0.61;-0.06) outperformed placebo. Ziprasidone 160&#xa0;mg/day, celecoxib 200&#xa0;mg/day, asenapine 20&#xa0;mg/day, and asenapine 10&#xa0;mg/day proved more efficacious than placebo in children. No statistically significant differences were reported between treatments and placebo for response/remission/acceptability/tolerability, and manic/hypomanic switch. A meta-regression of efficacy effect sizes against the adapted AMSTAR-Plus content scores showed that larger SMDs were associated with lower AMSTAR scores, indicating lower study quality, warranting further caution for such large efficacy estimates. CONCLUSIONS: Our findings are consistent with previous NMAs and current guidelines, expanding the current knowledge base while concurrently appraising different drugs, doses, and age groups.

Humans

Endovascular intervention for acute stroke in the very late window: A meta-analysis of 90-day mRS and procedural outcomes.

OBJECTIVE: This study investigates the effectiveness of Endovascular Therapy (EVT) in very late windows (beyond 24&#xa0;h) for patients with ischemic stroke, focusing on 90-day mortality, functional outcomes, and procedural success. METHODS: This systematic review and meta-analysis followed Cochrane and PRISMA guidelines to evaluate the effectiveness of endovascular therapy (EVT) in acute ischemic stroke patients. Literature from PubMed, Embase, Web of Science, and Scopus was reviewed using specific keywords. Studies included those after 2000 with outcomes such as functional independence (mRS 0-2), mortality, TICI scores, and neurological improvements. RESULTS: The data findings reveal mixed outcomes across studies on EVT beyond 24&#xa0;h. Sarraj et al. (2023) found a significant improvement in functional independence with EVT (38% vs. 10%, p&#xa0;<&#xa0;0.05), despite an increased risk of sICH. The forest plots for mRS and procedural outcomes show some significant results, such as Sarraj (2023) for mortality (p&#xa0;<&#xa0;0.05), but most other studies indicated no statistically significant differences (p&#xa0;>&#xa0;0.05). CONCLUSION: The study has concluded that Endovascular Therapy (EVT) beyond 24&#xa0;h can improve functional outcomes and reduce mortality in selected ischemic stroke patients, though patient selection remains crucial.

Humans