The evolving understanding of the regulation of allergic airway inflammation has offered new approaches for asthma therapy. For example, our understanding of the role of alarmins, Th2 cytokines and eosinophils has allowed the development of biologics that have revolutionized therapy for severe asthma. However, many questions remain and several of our patients are still not controlled with the current available therapies. Many immune cells have been implicated in asthma pathophysiology, but one cell that is missing from these studies is the monocyte. Monocytes (Mos) are bone marrow-derived cells that circulate in the blood and develop into macrophages and/or dendritic cells following migration to peripheral tissues. Macrophages (Møs) and dendritic cells have been implicated in the development and progression, of allergic airway inflammation, but also in tissue repair after inflammation. Recent studies in animal models suggest a major role for Mos in allergic airway inflammation, primarily through their ability to mediate recruitment of eosinophils and/or neutrophils to the airways. However, there is little information regarding the role of monocytes in human asthma. Here we review the literature regarding the presence and functions of peripheral blood and airway Mos in human asthma and suggest further work that needs to be done to consolidate the information on Mo functions. Studies show changes in Mo numbers and activation status in the peripheral blood of patients with asthma, changes that in many cases correlate with disease severity and/or activity. Studies also show altered phenotype of Mos present in the airways of patients with asthma. Detailed human studies need to be performed, if possible, studies that include therapeutic interventions, to allow for a full understanding of the role of Mos in asthma.

The decision to transfuse a patient with myocardial infarction (MI) and anemia at a higher vs lower hemoglobin threshold must consider the potential benefit of reduced risk of 30-day death or MI and the potential risk of heart failure.

To estimate bayesian posterior risk differences and posterior probabilities that a liberal vs restrictive transfusion strategy is associated with reduced risk of 30-day death or MI and whether the probabilities exceed predefined thresholds.

The Myocardial Ischemia and Transfusion (MINT) trial recruited adults from April 26, 2017, to April 14, 2023, who were hospitalized with MI and anemia at 144 sites in 6 countries. Statistical analysis was performed from July 31, 2024, to February 18, 2026.

The MINT trial randomized participants to a restrictive (transfuse if hemoglobin is <7 to 8 g/dL) or liberal (maintain hemoglobin at >10 g/dL) transfusion strategy.

Bayesian posterior risk differences were estimated for 30-day death or MI and for heart failure using 3 prior beliefs regarding the treatment strategies: noninformative, liberal strategy superiority, or restrictive strategy superiority.

The mean (SD) age of the 3504 participants was 72.1 (11.6) years and 1911 (54.5%) were men. Compared with the restrictive strategy, the risk of 30-day death or MI with the liberal strategy was 1.4% (95% credible interval, -0.8% to 3.5%) to 2.4% (95% credible interval, 0.3%-4.6%) lower, depending on prior beliefs. The probability that the liberal strategy was associated with a lower risk of 30-day death or MI ranged from 89.1% to 98.8%, and the probability that a liberal strategy was associated with at least 1 less death or MI per 100 treated was between 62.7% and 90.4%. Conversely, the risk of heart failure with the liberal strategy was 0.2% (95% credible interval, -1.6% to 1.2%) to 0.6% (95% credible interval, -2.0% to 0.8%) higher compared with the restrictive strategy, depending on prior beliefs. The probability that the liberal strategy was associated with a higher risk of heart failure ranged from 60.6% to 80.0%, and the probability that a liberal strategy was associated with at least 1 more heart failure event per 100 treated was between 13.3% and 29.3%.

This post hoc analysis of a randomized clinical trial of patients with MI and anemia suggests that a liberal transfusion strategy was associated with a lower risk of 30-day death or MI, outweighing the increased risk of heart failure. Consistent with guideline recommendations and according to patients' values and clinician risk assessment, a liberal transfusion strategy may be reasonable.

ClinicalTrials.gov Identifier: NCT02981407.

A robust chain of survival is important for achieving positive outcomes following out-of-hospital cardiac arrest, which continues to pose a substantial public health challenge in Singapore. Although improvements have been made in prehospital resuscitation and survival to hospital admission, further progress is required for survival to hospital discharge and neurological recovery. This underscores the urgent need to strengthen post-cardiac arrest care-the sixth link in the chain of survival-to optimise outcomes for patients admitted to the intensive care unit after return of spontaneous circulation. This review builds on earlier recommendations of the National Targeted Temperature Management Workgroup (2017) and the National Post-Cardiac Arrest and Survivorship Workgroup (2021), providing an updated summary of post-cardiac arrest management and practical guidance for clinicians treating resuscitated cardiac arrest patients in the intensive care unit.

Advanced cardiovascular life support (ACLS) provides a structured approach to the management of cardiac arrest and life-threatening arrhythmias, building on early recognition, high-quality cardiopulmonary resuscitation (CPR), and timely defibrillation. The 2026 Singapore ACLS guidelines present updated, evidence-based recommendations informed by the latest guidance from the American Heart Association and the European Resuscitation Council. Key updates include optimisation of CPR quality, integration of point-of-care ultrasonography, and refined use of pharmacological and electrical therapies during resuscitation. The role of extracorporeal CPR as a rescue strategy in selected patients and the importance of organised post-resuscitation care in improving neurological outcomes are emphasised. Management of tachyarrhythmias and bradyarrhythmias is also addressed. Special circumstances, including pulmonary embolism, drowning and cardiac arrest during pregnancy, are discussed. These guidelines aim to standardise practice and improve survival and functional outcomes following cardiac arrest in Singapore.

Basic cardiac life support and automated external defibrillation refer to the skills required for resuscitation of a cardiac arrest casualty. On recognising cardiac arrest, the rescuer should call '995' for an ambulance and start cardiopulmonary resuscitation. High-quality chest compressions are performed with the arms extended, elbows locked, shoulders directly perpendicular over the casualty's chest and the heel of the palm placed on the lower half of the sternum. The rescuer compresses to a depth of 4-6 cm for adults, at a rate of 100-120 compressions per minute, allowing complete chest recoil after each compression. Two quick ventilations of 400-600 mL each are delivered via a bag-valve-mask (or mouth-to-mouth or mouth-to-mask if trained and able) after 30 chest compressions (or 15 chest compressions for casualties under 12 years of age). Cardiopulmonary resuscitation should be stopped when the casualty regains consciousness, the emergency team takes over care, or when an automated external defibrillator analyses the heart rhythm or delivers a shock.

To evaluate the efficacy and safety of early aspirin discontinuation followed by P2Y12 inhibitor monotherapy versus standard dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).

This systematic review and meta-analysis followed PRISMA 2020 guidelines and a prespecified protocol registered in PROSPERO (CRD420261293472). MEDLINE, Embase, Scopus, and CENTRAL were searched through December 2025 for randomized controlled trials comparing early aspirin discontinuation (≤ 3 months) with standard DAPT in ACS patients undergoing PCI with drug-eluting stents. Two reviewers independently conducted study selection, data extraction, and risk of bias assessment (Cochrane RoB 2.0). Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were estimated using a random-effects model.

Seven trials including 20,501 patients (10,246 early discontinuation; 10,255 standard DAPT) were analyzed. Early aspirin discontinuation significantly reduced bleeding (RR, 0.46; 95% CI, 0.36-0.60; p < 0.001; I²=21.9%). There was no significant difference in major adverse cardiovascular events (RR, 0.98; 95% CI, 0.77-1.26) or in myocardial infarction, stroke, repeat revascularization, or all-cause mortality. However, early aspirin discontinuation was associated with an increased risk of stent thrombosis (RR, 1.72; 95% CI, 1.07-2.78). In trials with aspirin discontinuation within 1 month, bleeding reduction remained substantial, with numerically higher but nonsignificant ischemic outcomes.

In ACS patients undergoing PCI, early aspirin discontinuation reduces bleeding without a statistically significant increase in overall ischemic events; however, a significant increase in stent thrombosis was observed. These results support individualized decision-making, particularly favoring patients at high bleeding risk and low thrombotic risk treated with potent P2Y12 inhibitors. Further adequately powered studies focused on rare ischemic outcomes, including stent thrombosis, are warranted.

Orthopedic diseases impose heterogeneous therapeutic demands, ranging from symptomatic control of inflammation and pain to intra-articular drug delivery, cartilage repair, bone regeneration, and prevention of implant-associated infection. Although hydrogels are widely investigated as tunable biomaterials for these applications, their translational potential is often discussed primarily in terms of polymer composition or crosslinking chemistry. This review argues that delivery modality provides a clinically useful framework for evaluating orthopedic hydrogel systems, but translational success depends on the combined influence of material properties, mechanical requirements, degradation behavior, biological integration, manufacturability, and regulatory feasibility. Hydrogel patches, injectable hydrogels, and implantable hydrogels differ in tissue access, mechanical competence, payload capacity, residence time, invasiveness, and regulatory feasibility. Here, we critically compare these three delivery paradigms across major orthopedic indications. Hydrogel patches are best positioned for localized analgesic and anti-inflammatory therapy but remain poorly suited for deep regenerative delivery because of skin-barrier limitations. Injectable hydrogels can offer a strong balance between minimally invasive administration and localized therapeutic control, particularly for intra-articular disease and irregular defects, but require improved retention, mechanical stability, and predictable gelation. Implantable hydrogels can provide architectural and mechanical control for focal bone and osteochondral repair when designed as structural or composite systems, yet their clinical adoption is constrained by surgical burden, manufacturing complexity, and long-term durability requirements. By shifting the discussion from material cataloguing to indication- and delivery-modality-driven design, this review provides a balanced framework for evaluating orthopedic hydrogel technologies and identifies practical translational priorities related to tissue access, mechanical durability, biological response, manufacturing, and clinical feasibility.

Inflammation contributes to atherosclerosis and vascular remodeling, but the immune pathways associated with distinct carotid ultrasound phenotypes, including carotid intima-media thickness (cIMT), maximal plaque thickness (MPT), and arterial stiffness remain incompletely characterized. We investigated associations between circulating immune biomarkers and carotid ultrasound measures in a stroke-free, multi-ethnic cohort. We analyzed data from 1,134 stroke-free participants (mean age 70 ± 9 years, 59% women, 66% Hispanic) in the Northern Manhattan Study (NOMAS) who underwent high-resolution B-mode carotid ultrasound. cIMT and MPT were measured using automated edge-detection software, while arterial stiffness was assessed via systolic and diastolic diameter measurements, strain, and β-stiffness. Plasma levels of 60 immune biomarkers were quantified using a multiplex immunoassay. Biomarker selection was performed using LASSO, Random Forest, and XGBoost; markers selected by ≥ 2 methods were prioritized. Associations were tested using multivariable linear regression adjusted for age, sex, race/ethnicity, and cardiovascular risk factors (hypertension, hyperlipidemia, diabetes, and smoking). Machine-learning analyses identified partially distinct candidate biomarker profiles for cIMT, MPT, and arterial stiffness. In fully adjusted regression models, greater cIMT was associated with higher IL-4 and leptin levels and lower IL-10, VCAM-1, and SerpinE1 levels. None of the machine-learning-selected biomarkers was independently associated with MPT at the conventional p < 0.05 threshold. Greater arterial stiffness was associated with higher SCF levels, while CXCL10 demonstrated a nonsignificant inverse trend. Models incorporating the selected biomarkers had modestly higher adjusted R² values than models containing clinical covariates alone (cIMT, 0.072 versus 0.109; MPT, 0.134 versus 0.147; arterial stiffness, 0.063 versus 0.075). In a stroke-free, multiethnic cohort, machine-learning analyses identified distinct and overlapping candidate immune biomarker profiles across cIMT, plaque thickness, and arterial stiffness. However, only a subset of selected biomarkers demonstrated independent associations in fully adjusted regression models. These findings support a hypothesis-generating role for inflammatory and immunometabolic pathways in subclinical carotid disease and vascular aging and require validation in longitudinal studies.

ObjectiveSystemic lupus erythematosus is associated with increased cardiovascular morbidity, even in the absence of overt clinical disease. Sestrin-1 is a stress-responsive antioxidant protein implicated in oxidative homeostasis and cardiovascular protection. This study aimed to evaluate serum Sestrin-1 levels in patients with systemic lupus erythematosus and examine their relationship with subclinical cardiovascular findings.MethodsIn this controlled cross-sectional study, 60 patients with systemic lupus erythematosus and 60 age-matched healthy controls underwent clinical assessment, laboratory testing, 12-lead electrocardiography, transthoracic echocardiography, and carotid intima-media thickness measurement. Serum Sestrin-1 was measured by enzyme-linked immunosorbent assay (ELISA). Between-group comparisons used parametric or nonparametric tests according to data distribution. Within the systemic lupus erythematosus cohort, correlations between Sestrin-1 and disease activity (Systemic Lupus Erythematosus Disease Activity Index), as well as cardiovascular parameters, were assessed. An exploratory multivariable logistic regression model including Sestrin-1, left atrial diameter, corrected QT interval, age, and sex was constructed to identify variables associated with case status.ResultsSerum Sestrin-1 levels were significantly lower in patients with systemic lupus erythematosus than in controls (9.99 ± 2.01 vs. 17.79 ± 5.11 ng/mL; p < 0.001). Patients with systemic lupus erythematosus had a significantly longer corrected QT interval (429.65 ± 32.42 vs. 376.26 ± 33.41 ms; p < 0.001). In the exploratory multivariable logistic regression analysis, lower Sestrin-1 (per 1ng/mL increase, odds ratio 0.63; 95% confidence interval: 0.54-0.75; p < 0.001), larger left atrial diameter (per 1 mm increase, odds ratio 1.13; 95% confidence interval: 1.06-1.22; p < 0.001)), and longer corrected QT interval (per 1ms increase, odds ratio 1.03; 95% confidence interval: 1.02-1.05; p < 0.001) were independently associated with systemic lupus erythematosus status.ConclusionPatients with systemic lupus erythematosus exhibit markedly reduced serum Sestrin-1 levels together with subclinical cardiovascular abnormalities. The inverse relationship between Sestrin-1 and left atrial diameter suggests a possible link between reduced antioxidant defense and early atrial remodeling in systemic lupus erythematosus. Sestrin-1 may represent a promising candidate biomarker for subclinical cardiovascular involvement in patients with systemic lupus erythematosus; however, prospective studies are needed to confirm its clinical utility.

Older Aboriginal and Torres Strait Islander Australians are central to their communities, providing cultural leadership and care. However, colonisation and systemic inequities have led to significant health disparities, with chronic diseases and dementia disproportionately affecting those aged over the age of 55 years. This study aimed to develop a strengths-based framework to support healthy ageing in the Torres Strait and Northern Peninsula Area.

A participatory action research approach was conducted across five communities, involving yarning circles with 45 community members, clinical audits of 1128 residents using the Healthy Ageing Audit Tool (HAAT) and continuous quality improvement (CQI) initiatives. Findings informed the co-design of an Ageing Well Framework, refined through stakeholder workshops and community feedback.

The HAAT audit revealed high rates of chronic disease and multimorbidity among adults aged over 55 years, alongside gaps in preventive care, including low rates of cardiovascular risk and dementia screening and limited follow-up for abnormal findings. Continuous Quality Improvement (CQI) activities highlighted opportunities to improve culturally appropriate care, such as increased use of Indigenous Health Workers, validated screening tools and comprehensive health assessments. The co-designed Ageing Well Framework outlined strategies at community, primary health care and individual levels to promote cultural and social connectedness, independence and ageing in place.

The Ageing Well Framework provides a culturally responsive, evidence-based guide to improving health and well-being for older Aboriginal and Torres Strait Islander Peoples. It fosters collaboration across sectors and prioritises cultural determinants of health, supporting holistic care and addressing health inequities in the Torres Strait and Northern Peninsula Area (NPA).