The COVID-19 pandemic highlighted a global shortage of, and inequity of access to, medical oxygen. Understanding patient outcomes and the capacities of health facilities to provide respiratory support including oxygen is key to matching need and demand. We report results from a global study including 23 low-income and middle-income countries.

For this prospective, observational cohort study, consecutive patients aged 12 years or older with suspected or confirmed COVID-19 and evidence of respiratory distress were prospectively recruited within 24 h of hospital admission. Hospitals from 23 low-income and middle-income countries were included, representing all WHO regions. Baseline demographic and clinical data were collected, and daily follow-ups were recorded for in-hospital outcomes and respiratory support types. At the facility level, we assessed sources of oxygen and electricity, infrastructural and staffing capacity for critical care provision, and the capabilities of the facility for advanced respiratory support. The primary outcome was 30-day in-hospital mortality. This study was registered on ClinicalTrials.gov (NCT04918875).

Between Jan 24 and Nov 22, 2022, 56 sites took part. Of 53 726 patients screened, 3070 were enrolled. 1814 (61·6%) of 2947 patients had two or more underlying medical conditions and initially received oxygen through nasal cannula or non-rebreather face masks with reservoir. Invasive mechanical ventilation was most frequently used in patients recruited in the Americas (75 [26·4%] of 284 patients) and in the Eastern Mediterranean (90 [18·0%] of 499 patients). The overall mortality was 649 (23·4%) of 2779 patients, varying by region from 53 (10·5%) of 506 patients in South-East Asia to 286 (37·6%) of 760 patients in Africa. Mortality was associated with the maximum level of respiratory support received: from 17 (8·6%) of 198 patients who received no oxygen, 99 (38·4%) of 258 patients for non-rebreather reservoir bags, and 205 (62·9%) of 326 for invasive ventilation.

The availability and use of oxygen support options in low-income and middle-income countries are highly variable but appear significantly less in the African region. Mortality might be associated with a lack of access to oxygen, which varied across WHO regions but was highest in Africa. Despite many lessons learned from the COVID-19 pandemic, inequity in access to medical oxygen remains a challenge that WHO and partners must address in the post-pandemic era to avoid preventable deaths.

UNITAID.

Tuberculosis screening faces challenges of under-detection, costly approaches, and inequitable access. AI-enabled digital stethoscopes have demonstrated promising accuracy and feasibility for detecting lung and cardiovascular abnormalities, with promising results in early TB studies. Training and validation in diverse, high-burden settings are essential to explore the potential of this tool further.

We report the case of a 45-year-old woman who was referred to our Cardiology Department because of persistent exertional dyspnea and peripheral edema. She had an established clinical diagnosis of hereditary hemorrhagic telangiectasia with multiple gastrointestinal telangiectasias that had been submitted to repeat embolization in the past and arteriovenous malformations in the liver and lungs. Complete blood count was diagnostic for severe anemia (hemoglobin 5-6 g/dL). Since the hereditary hemorrhagic telangiectasia diagnosis 3 years prior, the patient informed us that she has undergone 27 blood transfusions and multiple embolizations to manage gastrointestinal telangiectasias. Given her severe anemia that was caused by gastrointestinal telangiectasia, treatment with bevacizumab was initiated. Bevacizumab was administered over 8 cycles (initially biweekly for 4 doses, followed by monthly administration).

A 74-year-old woman sought treatment with a 4-day history of high fever and rapidly progressive dyspnea. A 2-day course of ceftriaxone and betamethasone administered in an outpatient setting did not result in any clinical improvement, leading to her admission to our hospital. She demonstrated a slight cough but did not report heartburn, night sweats, hemoptysis, myalgia, arthralgia, or weight loss. Her family history was unremarkable.

Monoclonal antibodies ("biologics") have increasingly been used to manage chronic sinusitis with nasal polyps (CRSwNP). The aim of this manuscript was to compare biologic outcomes to traditional management of CRSwNP with endoscopic sinus surgery (ESS).

There are now four approved biologics for the treatment of CRSwNP in the United States: dupilumab, mepolizumab, omalizumab, and tezepelumab. Cost analysis and comparison between phase 3 clinical trial results of biologics and ESS show ESS is at least as effective as biologics in controlling symptoms with significantly less cost to the healthcare system. Recent guidelines published by the European Position paper on Rhinosinusitis and Nasal Polyps (EPOS) and the American Academy of Otolaryngology continue to support ESS in the management of CRSwNP when traditional medical therapy has failed. Biologics may be considered an option for severe uncontrolled CRSwNP that has failed comprehensive ESS. Future studies are needed to assess long-term efficacy and cost of biologics compared to ESS in CRSwNP.

The prognostic implications of Alberta Stroke Program Early CT Score (ASPECTS) subscores in patients with large-core ischemic stroke undergoing endovascular thrombectomy (EVT) remain uncertain. We hypothesized that specific ASPECTS regions substantially influence functional outcomes after EVT and therefore sought to identify which individual subscores are associated with outcome and whether any of them account for the association between total ASPECTS and functional outcomes. We retrospectively analyzed patients with large-core ischemic stroke (ASPECTS ≤ 5) who underwent EVT. Multivariate logistic regression identified factors associated with functional outcomes, and mediation analysis assessed whether specific ASPECTS subscores explains the effect of total ASPECTS on outcomes. Among 295 patients (median ASPECTS 4), 49.2% had a median mRS score of 3 at 3 months. Internal capsule (IC) involvement was the only subscore significantly associated with worse outcomes, including ordinal mRS shift (Odds ratio 2.03 [ 95% confidence interval 1.19‒3.46], P = 0.009), mRS ≥ 4 (3.01 [1.45‒6.24], P = 0.003), and mRS ≥ 3 (2.24 [1.03‒4.87], P = 0.042). Mediation analysis showed that IC involvement explained 50.6% of the total ASPECTS effect on outcomes. Patients with IC lesions showing reversal on follow-up imaging had a significantly lower risk of poor outcomes (0.28 [0.09-0.80], P = 0.018). IC involvement independently predicts poor outcomes after EVT for large-core stroke and substantially explains the effect of total ASPECTS on prognosis.

Hypertension, a major risk factor for cardiovascular disease, is largely regulated by the renin-angiotensin system (RAS). This study evaluates the multitarget potential of three amaranth-derived peptides -SFNLPILR, FNLPILR, and AFEDGFEWVSFK- previously identified as renin inhibitors. We assessed their ability to inhibit angiotensin-converting enzyme (ACE), modulate ACE2 activity, and their bioavailability. In vitro assays demonstrated that SFNLPILR and FNLPILR are potent ACE inhibitors (IC₅₀ = 0.075 and 0.055 mM, respectively), with selective or minimal modulation of ACE2 enzymatic activity. Bioinformatic analysis identified encrypted bioactive motifs with known ACE -inhibitory activity within their sequences. Molecular docking revealed that both peptides interact with ACE's catalytic residues through the LR motif. Additionally, transepithelial transport studies using Caco-2 monolayers confirmed that peptide fragments can cross the intestinal barrier. These findings position SFNLPILR and FNLPILR as promising multifunctional candidates for the development of functional foods aimed at reducing hypertension risk via RAS modulation.

Myocardial infarction remains a leading cause of mortality worldwide, primarily due to the limited regenerative capacity of adult cardiac tissue. Recent advances in regenerative medicine aim to address this limitation through stem cell therapies supported by bioengineered scaffolds and targeted delivery systems. This review highlights current progress in scaffold-guided cardiac regeneration, focusing on the therapeutic potential of embryonic, mesenchymal, induced pluripotent, and cardiac-resident stem cells. The integration of natural and synthetic biomaterials, including hydrogels, decellularized extracellular matrices, and smart polymers, is discussed in relation to cell survival, engraftment, and paracrine signaling. Moreover, we examine innovative delivery strategies, such as temperature-responsive cell sheets, injectable hydrogel systems, and 3D-printed constructs. Key challenges, including poor cell retention, immune rejection, and variability in scaffold performance, are addressed along with emerging solutions like bioresponsive materials and multimodal imaging for in vivo cell tracking. Finally, we propose translational perspectives to accelerate the clinical application of scaffold-assisted stem cell therapies for heart repair. Overall, this review synthesizes current advances and emerging technologies to provide a comprehensive roadmap for optimizing scaffold-based stem cell strategies in cardiac regeneration.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing public health concern that contributes to liver and cardiovascular complications. The prevalence of MASLD in women increases sharply around age 50 years, but the relationship between an earlier age at natural menopause and MASLD is unknown.

Using the TriNetX global federated network, we identified women with earlier menopause (< 50 years). The control cohort consisted of similarly aged pre-menopausal women. Cases of premature (< 40 years) or surgical menopause, non-MASLD causes of steatotic liver disease (SLD), or sex-hormone therapy were excluded. Propensity-score matching adjusted for baseline characteristics and metabolic risk factors, resulting in two matched cohorts of 20,979 women (total n = 41,958) in the final analysis. Outcomes included new diagnoses of MASLD (metabolic dysfunction-associated steatohepatitis) and the MASLD metabolic factors: pre-diabetes/diabetes, hypertension, dyslipidaemia, and overweight/obesity over 5 years of follow-up.

Earlier menopause was associated with an increased risk of developing MASLD (HR 1.322, 95% CI 1.170-1.492), new-onset dyslipidaemia (1.083; 1.045-1.122) and pre-diabetes (1.130; 1.060-1.205). Findings were consistent across stratified analyses by pre-existing metabolic risk factors (HR 95% CI for MASLD with pre-existing dysglycaemia 1.370, 1.042-1.800; dyslipidaemia 1.340, 1.053-1.705; hypertension 1.230, 0.998-1.516; overweight 1.280, 1.086-1.510).

Risk of MASLD is increased following menopause before age 50. Further studies should assess the incorporation of menopause timing into female-specific cardiometabolic risk assessment.

Metabolic dysfunction is increasingly recognized as an early contributor to the pathophysiology of dementia. Identifying blood-based biomarkers associated with preclinical disease changes may provide valuable insights into early disease mechanisms and potential intervention strategies. This study aimed to determine sparse metabolite signatures of dementia risk and to determine whether metabolites mediate the relationship between established modifiable risk factors and dementia using both observational and genetic epidemiology approaches.

This study included 271,610 participants from the UK Biobank (UKB), with 327 plasma metabolomic measures (168 absolute concentrations and 159 derived ratios) quantified per sample. A lasso-regularized Cox proportional hazards regression model was used to identify a signature of metabolites associated with the risk of all-cause dementia (ACD), vascular dementia (VaD), and Alzheimer's disease (AD). The metabolomic risk score (MRS) derived from metabolite signatures was evaluated for its association with brain structural changes. Mediation analysis was performed to assess whether metabolite signatures mediated the associations between established dementia risk factors and incident dementia. Finally, Mendelian randomization (MR) analyses including Multivariable MR were conducted to explore potential causal associations and mediating effect.

Metabolomic signatures predicted ACD, AD, and VaD with C-indices of 0.63, 0.65, and 0.69, respectively, and significantly improved predictive performance when adding to clinical factors (C-indices improvement 0.002-0.003). The VaD and ACD MRS showed widespread associations with most regional brain volumes and white matter microstructures. Glucose and the percentage of linoleic acid (LA%) were primarily responsible for mediating the association between obesity and ACD/VaD, with the proportion of mediation exceeding 30%. In MR analysis, albumin and glutamine were nominally associated with AD, and LA% was nominally associated with VaD. Finally, LA% significantly mediated the causal relationship between diabetes and VaD.

Metabolomic signatures improved dementia prediction beyond established clinical risk factors and mediated the relationship between these risk factors and dementia. MRS were strongly associated with volume changes in multiple brain regions. This study implicates early metabolic pathobiology in the development of dementia and may inform potential intervention strategies. Future research will employ advanced MR methods to further characterise these complex relationships.