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A myeloid-dormant metabolic transcriptome identifies a poor-prognosis subgroup in hyperdiploid multiple myeloma with targetable vulnerabilities.2 weeks agoAberrant metabolism, a hallmark of cancer, reveals vulnerabilities across human tumors. Here, we demonstrate that transcriptomic alterations of metabolism-related genes (metabolic transcriptome) in multiple myeloma (MM), classify patients into six metabolic-transcriptional groups characterized by specific metabolic pathways and cytogenetic alterations, independent of currently described myeloma risk groups. Interestingly, hyperdiploid patients clustered into 2 groups (MM5 and MM6) with significantly distinct Progression-Free and Overall Survival. The MM5 group, with worse prognosis, showed a significant enrichment in myeloid and dormant cell signatures. Regulon analysis identified myeloid transcription factors (TFs) as regulators of metabolic, myeloid, and dormant genes in MM5. In addition to myeloid genes acting as potential biomarkers and therapeutic targets, the metabolic gene ACSL1 plays a crucial role in MM5, decreasing cell proliferation by affecting metabolism and mitochondrial function, sensitizing MM to BCL-2 family inhibitors. These findings highlight ACSL1 as a promising therapeutic target for MM5 and provide new insights into MM metabolic heterogeneity that may guide future precision medicine strategies.CancerCardiovascular diseasesPolicy
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Preparedness, awareness and ownership of young future healthcare professionals are associated with their willingness to contribute to health system resilience in a NATO collective defense scenario: a cross-sectional study among medical, nursing and paramedic students in Germany.2 weeks agoRussia's war against Ukraine has renewed discussion about a possible NATO Article 5 collective defense scenario in Europe. In such a situation, Germany would function as key logistical and medical hub, placing substantial strain on its healthcare system. Experience from the COVID-19 pandemic suggests that health system resilience not only depends on infrastructure but also on availability and commitment of health professionals. This study examined willingness of future health professionals in Germany to contribute beyond routine duties in such a crisis and assessed preparedness, ownership, and awareness as potential determinants.
Between 20 May and 15 July 2025, a cross-sectional online survey was conducted among German medical, nursing, and paramedic students (n = 514). Data were collected on demographics and self-assessed individual preparedness, perceived institutional preparedness, voluntary engagement as major indicator of ownership, and awareness regarding a NATO collective defense scenario. Willingness to contribute beyond routine practice was assessed across preparatory activities, crisis-specific medical tasks, and modified working conditions. Composite scores were calculated for awareness, individual and institutional preparedness, and willingness. Associations with willingness were examined using multivariable linear regression adjusted for predefined covariates.
Overall, 48.8% considered a NATO collective defense scenario by 2030 likely, 83.3% anticipated negative effects on the German healthcare system, and 94.5% perceived the healthcare system as poorly prepared. Individual preparedness was low (median: 3 on 0-12 scale; IQR: 1-5), while recent voluntary engagement, including voluntary work during studies or apprenticeships in general or in civil aid organizations specifically, was common (59.1%). Participants showed high willingness to engage in preparatory measures and to provide care in Germany, but lower willingness to initiate trainings or to provide care for German or allied soldiers abroad. In adjusted regression analyses, higher perceived institutional preparedness, voluntary engagement, and awareness were significantly associated with greater willingness (all: p < 0.01).
Willingness of future health professionals to support the German healthcare system in a NATO collective defense scenario was associated with perceived institutional preparedness, awareness, and voluntary engagement. Widespread perceptions of insufficient preparedness raise concerns about system resilience, and the associated factors might represent potential targets for policy interventions.Chronic respiratory diseaseAccessAdvocacy -
Assessment of Lung Injury Based on the Decompression Scheme of Lung Toxicity Dose Unit and K Value.2 weeks agoThis study aimed to assess hyperoxic lung injury (HLI) during a heliox dive based on the unit pulmonary toxic dose (UPTD), K index, and equivalent surface oxygen time (ESOT).
The UPTD, K index, and ESOT values of each schedule in the Helium-Oxygen Decompression Table of China were calculated. Based on the recommended thresholds, the risk of lung injury was analyzed, and suggestions were proposed to modify certain schedules.
The K index and ESOT were more conservative than UPTD in predicting HLI. After a deeper dive, the UPTD, K index, and ESOT values were generally higher than the recommended thresholds. For schedules in which the UPTD, K index, and ESOT values do not exceed the thresholds, we recommend prolonging time on oxygen with or without reducing time on air, or recommending oxygen inhalation after surfacing, which may improve safety without increasing the risk of lung injury. For most schedules, the lung injury may resolve within 12 hours after surfacing, according to the K index.
Decompression schedules can be adjusted in real time according to K or ESOT values, which may improve safety while effectively controlling the risk of HLI.Chronic respiratory diseaseAccessCare/ManagementAdvocacyEducation -
Six anthropometric indicators and their associations with myocardial infarction and death in Swedish automotive industry male workers followed for 28 years.2 weeks agoOverweight, (body mass index (BMI), kg/m2) 25-30 and obesity (BMI 30+) have long been linked to an increased risk of myocardial infarction and mortality. To better assess abdominal adiposity, several indices have been developed. However, the risk associated with each index can vary across different populations.
This study aims to investigate which body measurement, if any, exhibits the strongest associations with MI, and mortality. In 1993, a cohort of 1,000 randomly selected middle-aged Swedish men participated in a nurse-led health examination. Body measurements were recorded together alongside blood pressure readings, and a fasting blood test was conducted. A follow-up study, spanning 28 years, utilized data from the national Myocardial Infarction Register (Swedeheart) and mortality data from the Swedish Cause of Death Register. The obesity indices included body mass index, waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), sagittal abdominal diameter (SAD), and sagittal abdominal diameter-to-height ratio (SADHtR). Cox proportional hazard models were employed to analyze the z-scores of the six body measurements both before and after adjusting for covariates, with outcomes assessed for first-time myocardial infarction (MI) and mortality.
Data were collected for 959 men. Significant correlations were found between the six body measurements, all were associated with cardiovascular disease risk factors, myocardial infarction, and mortality. However, after adjusting for the traditional risk factors, the association with cardiovascular endpoints was diminished or vanished. WHtR emerged as a more reliable indicator, with hazard ratios (HR) of 1.31 (95% CI 1.07-1.62) for myocardial infarction and 1.27 (95% CI 1.08-1.49) for all-cause mortality although the differences were marginal.
There is currently no consensus on which obesity indicator should be the preferred predictor of cardiovascular risk. In this study, the WHtR emerged as the more reliable predictor, albeit with marginal clinical significance.
In this population, after adjustment for traditional risk factors, WHtR proved to be a more reliable predictor for MI and mortality.Cardiovascular diseasesAccessCare/ManagementAdvocacy -
Prognostic value of admission D-dimer in acute pancreatitis: association with disease severity and clinical outcomes in a retrospective cohort study.2 weeks agoEarly risk stratification in acute pancreatitis (AP) is crucial for improving patient outcomes and guiding timely clinical management. D-dimer has emerged as a potential biomarker reflecting activation of coagulation and fibrinolysis and may assist in early risk stratification of patients with acute pancreatitis. However, its prognostic performance remains incompletely validated across different populations.
This retrospective cohort study included 200 adult patients diagnosed with acute pancreatitis between March 2023 and March 2024 at a tertiary care hospital. Disease severity was classified using the Revised Atlanta Classification. Admission serum D-dimer was measured within the first six hours after hospital presentation. Admission D-dimer levels were analyzed in relation to clinical severity, BISAP and Ranson scores, ICU admission, length of hospital stay, and in-hospital mortality. Statistical analyses included non-parametric tests, correlation analysis, logistic regression, and ROC curve analysis to evaluate predictive performance.
Two hundred consecutive patients, with a mean age of 58.1 ± 17.5 years and 54% male patients, were included in this study. Severity distribution showed 68.5% mild, 17% moderately severe, and 14.5% severe AP. Overall mortality was 7% (n = 14), and 56% (n = 112) required ICU admission. Admission D-dimer levels increased significantly with disease severity, with median values of 1534 ng/mL (mild), 1908.5 ng/mL (moderately severe), and 2960 ng/mL (severe). Non-survivors had markedly higher levels than survivors (3776.5 vs. 1663 ng/mL, p < 0.001). D-dimer showed significant positive correlations with BISAP (ρ = 0.6068), Ranson scores (ρ = 0.3425), and hospital length of stay. ROC analysis demonstrated good discriminatory ability for severe AP (AUC = 0.778; cutoff 2035 ng/mL) and good discriminatory performance for mortality prediction (AUC = 0.912; cutoff 2726 ng/mL, sensitivity 85.7%, specificity 80.1%). However, performance for predicting ICU admission was limited (AUC = 0.579). Multivariable analysis demonstrated that each 1-ng/mL increase in admission D-dimer level was independently associated with higher odds of severe AP (OR = 1.001, p < 0.001).
Admission D-dimer is a simple and rapid biomarker associated with disease severity and mortality in acute pancreatitis. While it should not replace established scoring systems, it can serve as a valuable adjunct for early risk stratification, particularly for identifying high-risk patients. Prospective multicenter studies are needed to validate its clinical utility and define standardized cutoff values.Cardiovascular diseasesAccessCare/ManagementAdvocacy -
Neurological prognostication after cardiac arrest: evidence review and institutional protocol proposal.2 weeks agoCardiac arrest (CA) is associated with high mortality and neurological morbidity, mainly due to hypoxic-ischemic encephalopathy. Accurate neurological prognostication in CA survivors is essential to guide therapeutic decisions and provide appropriate care.
To review the current evidence on neurological prognostication after CA and to propose an institutional protocol adapted to the resources of Hospital de Clínicas de Porto Alegre (HCPA).
The current narrative review was conducted in two stages: a literature review and the development of an institutional protocol. Articles were selected according to their clinical relevance and their contribution to current evidence on neurological prognostication after CA. The PubMed, Scopus, Web of Science, Embase, and SciELO databases were searched. The protocol was developed considering the clinical tools available at HCPA, including neurological examination, electroencephalography (EEG), and neuroimaging.
Brain injury after CA occurs in three stages: intra-arrest ischemia, immediate reperfusion, and delayed postreperfusion injury. Prognostic modalities include neurological examination, EEG, somatosensory-evoked potentials (SSEPs), serum biomarkers, and neuroimaging. Reliable predictors of poor outcome include absent brainstem reflexes at 72 hours, persistent EEG suppression, bilateral absence of cortical N20 potentials, and diffuse abnormalities on magnetic resonance imaging. The proposed protocol organizes assessments from admission to the Intensive Care Unit through day 5 after the return of spontaneous circulation.
A standardized post-CA neurological prognostication protocol at HCPA may improve care quality, enhance communication with families, and support ethically-sound decision-making.Cardiovascular diseasesAccessCare/Management -
Aneurysmal subarachnoid hemorrhage: predictive score for angiographic vasospasm.2 weeks agoAneurysmal subarachnoid hemorrhage is a condition resulting from the rupture of a cerebral aneurysm, sometimes leading to delayed cerebral ischemia, primarily due to angiographic vasospasm; its prediction is crucial to improve patient management and outcomes.
To assess the predictive value of clinical, analytical and imaging parameters for vasospasm in aneurysmal subarachnoid hemorrhage and to develop a clinical practical score.
The current single-center retrospective study included 115 patients with aneurysmal subarachnoid hemorrhage who underwent a computed tomography scan within 24 hours of ictus. Clinical and analytical data were collected, and Hounsfield unit (HU) measurements were independently assessed. Statistical analyses were conducted to identify predictors of vasospasm.
Vasospasm occurred in 40% of patients (46/115). The multivariate analysis identified intracerebral hemorrhage (odds ratio [OR] = 2.482; 95%CI = 1.019-6.046; p = 0.045), interpeduncular HU value (per 5 HU increase: OR = 1.253; 95%CI = 1.044-1.504; p = 0.016), and serum chloride ≥ 106 mEq/L (OR = 3.545; 95%CI = 1.457-8.621; p = 0.005) as independent predictors (p < 0.05) of vasospasm. The model, combined as a simplified score including these 3 variables, demonstrated excellent discriminative capacity (area under the curve [AUC] = 0.886; bootstrapped AUC = 0.885).
We identified significant predictors of vasospasm in patients with aneurysmal subarachnoid hemorrhage, namely interpeduncular HU value, intracerebral hemorrhage, and serum chloride levels. A practical 5-point score based on these factors offers a potentially-robust, easy-to-use tool for early risk stratification, which may guide personalized follow-up and timely interventions. Further prospective multicenter studies are recommended to validate these findings.Cardiovascular diseasesAccessCare/ManagementAdvocacy -
Time-Dependent Efficacy of Hyperbaric Oxygen Therapy in Central Retinal Artery Occlusion.2 weeks agoTo determine the effect of the timing of hyperbaric oxygen (HBO₂) treatment on functional and structural outcomes in central retinal artery occlusion (CRAO).
This single‑center retrospective cohort study analyzed 101 eyes with CRAO treated with HBO₂. Eyes were stratified by symptom‑to‑treatment interval: ≤12 hours (Group 1), 12-24 hours (Group 2), 24-36 hours (Group 3), and >36 hours (Group 4). Best‑corrected visual acuity (BCVA-logMAR), central macular thickness (CMT), and inner retinal hyperreflective band thickness (IRHBT) were recorded at presentation, week 1, and month 6.
Presentation BCVA was 2.16 ± 1.04, improving to 1.77 ± 1.02 at month 6 (p = 0.03). The mean BCVA gain was greatest in Group 1: -0.85 ± 0.96, and declined markedly with delayed treatment initiation (Group 2: -0.48 ± 1.38; Group 3: -0.10 ± 1.50; Group 4: -0.08 ± 1.77). In Group 1, the mean BCVA improved significantly from 2.04 ± 0.78 logMAR at presentation to 1.19 ± 0.56 logMAR at the 6-month follow-up (p = 0.02). Early treatment was also associated with more pronounced reductions in CMT and IRHBT, whereas anatomical changes were negligible when therapy was initiated beyond 24 hours. Baseline CMT and IRHBT showed modest but significant correlations with final BCVA (r = 0.37, p = 0.03 , and r=0.34, p=0.04, respectively).
HBO₂ provides a significant, time-sensitive benefit for CRAO; initiating treatment within 12-24 hours maximizes recovery and retinal remodeling, validating HBO₂ as a critical adjunct and necessitating rapid triage in ophthalmic emergencies.Cardiovascular diseasesAccessCare/ManagementAdvocacy -
Cell-resolved testing of network-pharmacology candidates in dilated cardiomyopathy: PI3K-AKT-associated transcriptional differences are distributed across cardiac lineages and are not enriched above a genome-wide background.2 weeks agoNetwork pharmacology nominates targets but cannot show that they are altered in the relevant cell, distinguishable from a hypothesis-free analysis of the same data, or linked to disease. Taking the candidates nominated for Yangxin Decoction in dilated cardiomyopathy (DCM) and viral myocarditis, we asked how many survive independent functional-genomic testing. Few did. A direct-evidence intersection returned 61 genes, but across four bulk cardiac datasets the set was differentially expressed no more often than the transcriptome-wide background in any human cohort, and AKT1 was significant in none. Donor-pseudobulk single-nucleus RNA sequencing of 52 DCM and 18 control donors showed higher AKT1 (log2 fold change 0.351, adjusted P = 3.32 × 10- 4), PIK3CA and GSK3B and lower STAT3 in cardiomyocytes; no fold-change threshold was applied, and the AKT1 difference is small. These differences were robust to nucleus depth, sex, age, ventricle and DCM genotype; in an independent single-nucleus DCM cohort AKT1 (0.530) and STAT3 (- 0.771) replicated at FDR < 0.05, PIK3CA was directionally consistent, and GSK3B did not replicate. Three further tests constrain the interpretation. A disease × cell-type interaction model showed that PIK3CA is altered in most cardiac lineages and significantly more in fibroblasts than in cardiomyocytes, endothelial or immune populations, whereas the AKT1 difference, although significant only in cardiomyocytes, could not be shown to differ from that in most other lineages, so it reflects detection rather than demonstrated restriction. A whole-heart pseudobulk of the same donors still detected AKT1 (adjusted P = 6.8 × 10- 3), so cellular dilution does not explain the negative bulk-microarray result. Benchmarked against an unbiased genome-wide analysis of the same cardiomyocyte comparison, the nominated 61-gene set was not enriched (46.7% versus a 41.3% background, P = 0.281) and AKT1 ranked 2,182 of 14,586. A prespecified screen found no cis-eQTL instrument for AKT1; a single whole-blood MTOR Wald ratio was not supported by colocalization. These are cell-type-resolved transcriptional differences in dilated cardiomyopathy, not evidence that Yangxin Decoction engages PI3K-AKT signalling and not a validated therapeutic mechanism.Cardiovascular diseasesCare/Management
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Vascular-device suit concordance: a tri-ecological framework for eco-rebalancing.2 weeks agoPanvascular intervention can restore lumen patency, exclude structural defects, or replace diseased valves, but procedural success does not reestablish ecological stability within the treated vessel. We propose eco-rebalancing as a tri-ecological framework in which durable device performance depends on coordinated recovery across three domains: the mechanical, cellular, and physicochemical-immune ecologies. Vascular-device suitcordance denotes the spatiotemporal match between a device's mechanical behavior, biological interface, and material persistence, and the healing trajectory of a specific vascular bed, lesion, and patient; we introduce the Suitcordance Score (Su-Score) as a conceptual metric of that match. This perspective reinterprets restenosis, thrombosis, fibrosis, calcification, and structural degeneration as signatures of incomplete eco-rebalancing, providing a translational basis for device design and patient-device matching.Cardiovascular diseasesCare/Management