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At least 19 recordsLinked to original sources

Examining Transcriptomic Markers Associated With Neutrophil Extracellular Traps to Predict Mortality Risk in Neonatal Sepsis.

BACKGROUND: Neonates are highly susceptible to sepsis, which is often accompanied by fatal coagulopathy. Anticoagulant therapies have not reduced sepsis-related mortality in clinical trials, possibly due to patient heterogeneity. Neutrophil extracellular traps (NETs) enhance coagulation by activating platelets, suggesting that NET-specific biomarkers may identify patients who may benefit from targeted anticoagulant treatment. This study evaluated the association between NET gene expression and adverse outcomes in neonatal sepsis. METHODS: We analyzed whole blood transcriptomes from 123 neonates with sepsis and developed a predictive model, the NET score, based on NET-related gene expression. Model performance was assessed in two independent validation sets. Mediation and correlation analyses explored the relationship between the NET score and a coagulation score. Temporal transcriptomic data from septic shock cases further tested this interaction. RESULTS: The NET score achieved AUCs of 88.7% and 85.4% in validation Sets 1 and 2, respectively, indicating strong predictive performance. Mediation and temporal analyses supported a sequential relationship between NETosis and coagulation in sepsis. Age-specificity of the model was confirmed using pediatric (n = 163) and adult (n = 86) sepsis transcriptomic datasets. Neonates with disseminated intravascular coagulation exhibited a trend toward elevated NET scores. CONCLUSIONS: Our findings support a novel risk stratification approach using the NET score to identify neonates at increased risk for sepsis-associated coagulopathy and poor outcomes, potentially guiding targeted therapeutic strategies.

neonatal sepsis

Comparison of methods of predicting burn mortality.

Recent suggestions that patients "hopelessly burned" be permitted to die peacefully have refocused attention on the accuracy of different methods of predicting whether an individual burn patient will survive. The purpose of this presentation is to compare the accuracy of mortality predictions based upon four different statistical methods: (1) Baux's rule which adds the patient's age in years to the percentage of his body surface area burned--the original assertion was that values over 75 meant a very poor prognosis. (2) probit analysis, (3) discriminant analysis, and (4) logistic risk function analysis. Each of these methods was applied to data for over three thousand consecutive admissions to St. Mary's Hospital Burn Center in Milwaukee, Wisconsin. This data base and the four statistical models are described. Mortality predictions derived from the four models are compared, and some observations are made concerning the selection of an appropriate model for predicting burn mortality.

Adolescent

Predicting 5-Year Mortality in Non-Small-Cell Lung Cancer Using the Korean Central Cancer Registry: Model Development and Validation Study.

BACKGROUND: Non-small-cell lung cancer (NSCLC) is one of the most common cancers and a leading cause of cancer-related mortality, making prognostic prediction clinically essential. Machine learning models are increasingly used to assess prognosis; however, developing systems that combine high discrimination with clear, clinically interpretable reasoning remains challenging. OBJECTIVE: This study aimed to develop deep learning models that predict 5-year mortality in NSCLC using data from the Korea Central Cancer Registry and quantify feature importance through permutation testing. METHODS: We identified 3144 patients diagnosed between 2014 and 2017 who had complete clinical data, pulmonary function test results, histological information, genomic data, and staging details. After preprocessing, the cohort was divided into stratified training, validation, and test sets in a 70%-15%-15% ratio. Five models were tuned using Hyperband across 10 predefined feature groups. The primary evaluation metric was the area under the receiver operating characteristic curve (AUC); additional metrics included accuracy, F1-score, precision, and recall. Groupwise permutation importance was calculated for each model, and the concordance of importance rankings was assessed using the Friedman test. RESULTS: All 5 models yielded comparable discrimination values on the test set (AUC=0.875-0.879). Model A was selected as the primary model and achieved an AUC of 0.879, an accuracy of 0.806, an F1-score of 0.824, and a Brier score of 0.142. Permuting the stage resulted in the largest decrease in AUC (0.217), followed by the pulmonary function test (0.016). Gene mutation had a modest overall impact but became more influential within the adenocarcinoma subset. The Friedman test showed no statistically significant differences in importance rankings across the models (P=.93). CONCLUSIONS: A grouped-input deep learning framework achieved discrimination comparable to a conventional Cox proportional hazards model using the same routine clinical variables for 5-year mortality prediction in NSCLC. Group-level permutation importance provided stable and reproducible insights into the clinical factors influencing risk, which may guide future model refinement and clinical decision-making.

Humans

Social isolation and 59 common health conditions: insights from observational and genetics analyses.

BACKGROUND: The impacts of social isolation on diverse health conditions and how it contributes to health risks remain unclear. We aimed to investigate the associations of social isolation with 59 health conditions among older adults. METHODS: Participants from the UK Biobank without baseline diagnosis of the included diseases were selected. Social isolation was assessed with three questions. The 59 health conditions included all-cause mortality, 5 cause-specific mortalities, and 53 diseases. We used an instrumental variable from multivariable common factor GWAS in Mendelian randomization (MR) to explore causal links of social isolation with diseases. Omics analyses were conducted to assess the roles of Olink plasma proteins and metabolomics, and PERM was calculated to evaluate the influence of other factors. RESULTS: A total of 489,741 individuals [266,706 (54.5%) women; mean age 56.5 years (SD 8.1)] were included. During a median follow-up of 12.5 years, social isolation was uncorrelated with the majority of 59 health conditions. Significantly, it was associated with increased risks of all-cause [adjusted HR (aHR) 1.28, 95% CI 1.25-1.32], 5 cause-specific mortalities (aHR range, 1.18-1.38), and 11 specific diseases (aHR range, 1.08-1.17). Living alone was the strongest item of isolation in predicting mortality (aHR range, 1.18-1.45) and selected diseases. MR analyses offered little evidence to support a causal link between social isolation and these diseases. The proteins involved in these associations are predominantly related to "response to stimulus". Proteomic signatures (PERM, 36%-49%), health behaviours (32%-59%), and socioeconomic factors (22%-42%) were the main explanatory factors linking social isolation to 8 health outcomes. CONCLUSIONS: Social isolation is associated with elevated risks of 17 out of the 59 examined adverse health outcomes, predominantly mortality-related conditions; however, MR analyses indicate an absence of evidence supporting causality for these associations.

Humans

Wilms' tumor: prognostic factors for patients without metastases at diagnosis: results of the National Wilms' Tumor Study.

Multivariate statistical analyses are used to evaluate a wide range of factors in predicting relapse and survival for 429 children enrolled in the National Wilms' Tumor Study. Anaplastic or sarcomatous histology, specimen weight over 250 grams, positive regional lymph nodes, treatment with only a single drug and age over two years are the most important predictors of relapse. The first three factors also predict mortality. Laterality, capsular penetration, intrarenal vascular invasion, direct regional extension and operative spillage have lesser effects which do not contribute significantly to the multivariate prediction equations, while sex, race and the presence of a tumor thrombus in the renal vein have essentially no effect. Treatment with combination chemotherapy is confirmed to be efficacious regardless of what prognostic factors are operating. A statistical model allows prediction of relapse and death for each of 24 patient subgroups, with the estimates of percentage relapsed ranging from 3% to 100%.

Child

Acute hydrocephalus and death one month after non-surgical treatment for acute cerebellar hemorrhage. Case report.

Acute cerebellar hemorrhages, treated medically with subsequent complete recovery, have been designated "benign cerebellar hemorrhages." Ordinarily, acute cerebellar hemorrhage does require early surgical intervention and reported surgical mortality is relatively low (17%) in awake patients with this lesion. Clinical studies have shown that, after a period of approximately 2 weeks, the predicted mortality for this disorder becomes less than the operative mortality, and patients are then expected to recover. The author reports a case, with serial computerized tomography scanning, in which deterioration and death occurred 4 weeks after acute cerebellar hemorrhage. It is concluded that surgical intervention should be considered early in the clinical course of all cases of acute cerebellar hemorrhage.

Acute Disease

Serum Albumin on Admission: A Prognostic Marker of Morbidity and Mortality in Burns? A Systematic Review and Meta-Analysis.

Albumin is essential for maintaining oncotic pressure and vascular integrity. In burn injuries, increased capillary permeability leads to hypoalbuminemia, which is a recognized marker of poor outcomes in critical illness. However, its prognostic value in acute burn care remains underexplored. This study evaluated the prognostic value of admission serum albumin in predicting mortality, acute kidney injury (AKI), hospital and intensive care unit length of stay, ventilatory requirements, sepsis, and pulmonary infection in patients with burn injuries. A systematic search of PubMed, Scopus, Cochrane Library, Web of Science, MEDLINE, and Embase was conducted. Of 5587 studies screened, 19 were included in the systematic review and 9 in the meta-analysis. Statistical analysis was performed using RStudio, with pooled outcomes reported as odds ratios (ORs), standardized mean differences, and hierarchical summary receiver operating characteristic curves. Heterogeneity was assessed using Cochran's Q, I2, and tau2. Hypoalbuminemia on admission was significantly associated with increased mortality during admission (OR 9.51; 95% CI, 3.04-29.78; I2 49.3%). Admission hypoalbuminemia was also associated with an increased risk of AKI (OR 2.83; 95% CI, 2.49-3.22; I2 0%). Evidence for other outcomes was limited and heterogeneous. Admission serum albumin appears to be a valuable prognostic marker in patients with burn injuries, particularly for mortality and AKI. Further research is required to support its integration into burn-specific risk models, characterize albumin trends within the first 24 h postinjury, and establish optimal cut-off values.

Humans

Hypoxaemia and mortality in children with lower respiratory infection in low-income and middle-income countries: systematic review and meta-analysis.

BACKGROUND: Hypoxaemic lower respiratory infections (LRIs) are a leading cause of childhood mortality, with the highest burden in low-income and middle-income countries (LMICs). Hypoxaemia-low peripheral capillary oxyhaemoglobin saturation (SpO2)-is a marker of severity, and WHO recommends hospitalisation and oxygen administration for patients with SpO2 <90%. We aimed to update estimates from a 2015 systematic review and meta-analysis examining the association between hypoxaemia and mortality among children with LRIs in LMICs by incorporating studies published over the subsequent decade and evaluating mortality risk across multiple SpO2 thresholds. METHODS: We conducted a systematic review with meta-analysis by searching PubMed, Embase, LILACS, Global Index Medicus, Web of Science, and Scopus for peer-reviewed studies published between Jan 1, 2015, and June 18, 2025, with combined terms related to pneumonia, children, mortality, and LMICs. We also included selected earlier studies through citation checking. Eligible studies reported associations between hypoxaemia and mortality in children younger than 5 years with LRIs in LMICs. We excluded case reports and case series with fewer than five deaths, studies focused exclusively on the neonatal period, and those limited to children with specific comorbidities or to postoperative patients, for consistency with the original review. Two reviewers independently screened studies, extracted data, and assessed quality. Eligible studies were combined with those from the original review and analysed using random-effects models to estimate odds ratios (ORs) by hypoxaemia threshold subgroup. The protocol was registered on PROSPERO (CRD42023433946). FINDINGS: We identified 7734 records; 26 new studies met inclusion criteria and were combined with 18 from the original review. The 44 studies were published between 1993 and 2024 and were primarily from Africa (25 [57%] of 44) or Asia (19 [43%]); some studies spanned multiple locations. Data from 33 studies including 155&#x2009;633 participants were included in the primary meta-analysis. Hypoxaemia of any threshold was associated with higher odds of LRI mortality (OR 4&#xb7;36 [95% CI 3&#xb7;52-5&#xb7;39]) compared with no hypoxaemia. For SpO2 <90% versus 90-100%, OR for death was 4&#xb7;75 (95% CI 3&#xb7;42-6&#xb7;58). For SpO2 90-94% versus 95-100%, mortality risk was more than twice as high (OR 2&#xb7;27 [95% CI 1&#xb7;22-4&#xb7;25]). Heterogeneity was substantial (I2 64-85% across analyses), and eight (24%) of 33 studies in the primary meta-analysis had a high overall risk of bias; however, a sensitivity analysis restricted to studies with low or moderate risk of bias yielded similar results. INTERPRETATION: SpO2 <90% strongly predicts mortality in children with LRIs in LMICs. Children with SpO2 90-94% also have elevated risk, suggesting that paediatric LRI and pneumonia treatment algorithms should consider management at this hypoxaemia threshold. FUNDING: None.

Journal Article

Prognostic value of exercise testing soon after myocardial infarction.

The prognostic value of a limited treadmill exercises test performed one day before hospital discharge after acute myocardial infarction was studied in 210 consecutive patients who had no over heart failure and had been free of chest pain for at least four days. No complications occurred. During a one-year follow-up period 28 of 43 patients (65 per cent) who had chest pain during the test reported angina, as compared with 60 of 167 (36 per cent) who had no chest pain during test (P less than 0.001). The one-year mortality rates were 2.1 per cent (three of 146) in patients without changes in the S-T segment during exercise and 27 per cent (17 of 64) in those with depression of the S-T segment (P less than 0.001). Sudden death occurred in one of 146 (0.7 per cent) patients who showed no change in the S-T segment and in 10 of 64 (16 per cent) with depression of the segment (P less than 0.001). Thus, a limited treadmill exercise test performed before hospital discharge after acute myocardial infarction is safe and can predict mortality in the subsequent year.

Adult

Sex-Chromosome-Dependent Ageing in Female Heterogametic Methylomes.

Recent research in humans and both model and non-model animals has shown that DNA methylation (DNAm), an epigenetic modification, is one of the mechanisms underlying the ageing process. DNAm-based indices predict mortality and provide valuable insights into biological ageing mechanisms. Although sex-dependent differences in lifespan are ubiquitous and sex chromosomes are thought to play an important role in sex-specific ageing, they have been largely ignored in epigenetic ageing studies. We characterised the genome-wide distribution of age-related CpG (Cytosine-phosphate-Guanine) sites from longitudinal samples in two avian species (zebra finch and jackdaw), including for the first time the avian sex chromosomes (Z and the female-specific, haploid W). In both species, we find a small fraction of the CpG sites to show age-related changes in DNAm with the majority of them being located on the haploid, female-specific W chromosome, where DNAm levels predominantly decrease with age. Age-related CpG sites were over-represented on the zebra finch but under-represented on the jackdaw Z chromosome. Our results highlight distinct age-related changes in sex chromosome DNAm compared to the rest of the genome in two avian species, suggesting this previously understudied feature of sex chromosomes may be instrumental in sex-dependent ageing. Moreover, studying the DNAm of sex chromosomes might be particularly useful in ageing research, facilitating the identification of shared (sex-dependent) age-related pathways and processes between phylogenetically diverse organisms.

Animals

QT time in patients treated with alprenolol or placebo after myocardial infarction.

Studies were made on the effects of long-term beta-blockade on the QT interval in patients discharged alive from hospital after myocardial infarction. The patients (n = 230) in this study constituted all those who participated in the alprenolol study on postmyocardial patients in Göteborg, Sweden. The study was double-blind (alprenolol 200 mg b.i.d. or placebo) and randomised. The patients were divided into 4 risk groups (1-4) with different predicted mortality. The electrocardiograms before and after 8 weeks of treatment were analysed with respect to heart rate and QT time. There was a decrease in heart rate of about 10% in the alprenolol treated patients. The QT time was not significantly influenced by alprenolol. The rate corrected QT time (QTc) decreased in the subgroup of the most severely diseased patients (subgroup 4) treated with alprenolol.

Aged

Systematic review of machine learning approaches for predicting sickle cell crisis and mortality risk at the climate-health nexus.

BACKGROUND: Sickle cell anemia (SCA) is a severe genetic blood disorder characterized by recurrent vaso-occlusive crises and increased mortality, with the greatest burden occurring in low- and middle-income countries. Climatic and environmental conditions, including temperature variability, humidity, rainfall, air pollution, and seasonal changes, have been associated with disease exacerbation. However, the extent to which these factors have been incorporated into predictive models remains unclear. This study systematically reviews the application of machine learning (ML) models for predicting SCA crises and mortality in relation to climate and environmental factors. METHODOLOGY: The PRISMA guidelines were used, and 34 peer-reviewed studies published between 2005 and 2026 were analyzed to identify the climate variables, ML approaches employed, and predictive performance. The reviewed studies applied a range of ML techniques, including artificial neural networks, random forests, support vector machines, decision trees, logistic regression, and deep learning models. Temperature, humidity, rainfall, wind speed, air quality indicators, and seasonal patterns were the most frequently examined environmental variables. RESULTS: The findings indicate that most existing models rely predominantly on clinical and demographic data, with limited integration of climate information and inadequate representation of high-burden regions, especially Sub-Saharan Africa. Studies incorporating environmental variables reported improved predictive performance and highlighted the potential of climate-informed early warning systems for SCA management. CONCLUSION: The review recommends development of interdisciplinary, climate-aware ML frameworks, expansion of longitudinal environmental datasets, and increased research in underrepresented regions to support climate-resilient and patient-centered SCA care.

Humans

The effects of tildrakizumab in the epigenetic aging deviation of psoriasis: A 52-week open-label study.

BACKGROUND: While biologic therapies targeting interleukin-23 control cutaneous inflammation in psoriasis, their impact on epigenetic aging has not been previously demonstrated. OBJECTIVES: To evaluate the effects of tildrakizumab treatment in the epigenetic aging deviation of moderate-to severe psoriasis. METHODS: In an open-label 52-week clinical trial, 20 adults with psoriasis were treated with tildrakizumab-asmn 100 mg injections until week 28. Ten age-matched controls without psoriasis were enrolled. Genome-wide DNA methylation was profiled in peripheral blood leukocyte DNA (MethylationEPICv2.0, Illumina) to calculate epigenetic aging clocks predictive of all-cause-mortality, phenotypic age, chronological age, pace of aging, and telomere length. Epigenetic age deviation was calculated as the residuals against chronological age. RESULTS: Psoriasis patients had increased epigenetic age deviation in clocks predictive of mortality: PCGrimAge (P = .008), cytosine-phosphate-guanine (CpG) PTPCGrimAge3 (P = .019), CpGPTGrimAge3 (P = .019), GrimAge2 (P = .049). PCGrimAge was reversed by 0.3 years (week 28, P = .005) and 0.5 years (week 52, P = .04) after the use of tildrakizumab-asmn. The pace of aging was increased in psoriasis patients: DunedinPACE (P = .049). LIMITATIONS: Pilot study (small sample size). CONCLUSIONS: Psoriasis patients presented accelerated epigenetic aging in mortality-predictive clocks. Treatment with tildrakizumab-asmn (interleukin-23 inhibition) showed partial reversal of those clocks in 28 weeks. (Funded by Sun Pharmaceutical Industries, Inc; ClinicalTrials.gov number, NCT05110313).

DNA methylation clocks

Echocardiography in acute myocardial infarction.

Sixty-four patient with acute transmural myocardial infarction had daily echocardiograms while in the coronary care unit. Patients with previous infarction were excluded. The electrocardiographic site of infarction was anterior wall in 28, inferior wall in 33 and both anterior and inferior wall in 3 patients. Echocardiograms satisfactory for interpretation were obtained in 92 percent of cases. Abnormal left ventricular wall motion corresponding to the electrocardiographic site of infarction was seen in the echocardiogram in 84 percent of cases. Exaggerated normal motion in noninfarcted areas was seen in 30 percent. The left ventricular internal dimension correlated with clinical heart failure (P less than 0.005) and was increased in 50 percent. Abnormal mitral valve closure, which reflects increased left ventricular end-diastolic pressure, was present in 33 percent. This finding did not correlate significantly with clinical heart failure. By combining the measurements of left ventricular internal dimension and mitral valve closure, it was possible to predict hospital mortality from the echocardiograms. The results indicate that echocardiography is a useful technique in the study and management of patients with acute myocardial infarction.

Acute Disease

Immature Neutrophil Programs Associate With Burn Mortality and Extend Across Critical Illnesses.

Severe burns provoke a systemic "genomic storm," yet cell states associated with divergent outcomes remain unclear. We profiled blood cells by single-cell RNA-Sequencing (73&#x2009;014 cells) from adult patients with burn injuries within postburn day 17 (n&#x2009;=&#x2009;4) and healthy donors (n&#x2009;=&#x2009;5), integrated data with bulk signatures of burn size, inhalation injury, and mortality, and evaluated clinical associations in the American Burn Association National Burn Repository. Burn was associated with emergency hematopoiesis marked by expansion of hematopoietic stem/progenitor-like cells, immature neutrophils, and plasmablast/plasma cell states, alongside depletion of na&#xef;ve CD4+/CD8+ T cells and dendritic cells. Larger burns (>20% TBSA) showed enrichment of humoral transcriptional programs, including plasmablast/plasma cell activation and suppression of cytotoxic CD8+ T-cell states. In multivariable models, inhalation injury was a stronger predictor of death (adjusted odds ratio [OR] 1.9) than burn size (adjusted OR 1.1) and shared greater overlap with the most perturbed single cells in non-survivors; 55% of co-perturbed cells were neutrophils, implicating granulocyte dysregulation as a common lethal axis. We identified a neutrophil-specific 5-gene panel (OLFM4, RETN, LCN2, ARG1, and BTNL3) that discriminated survivors vs non-survivors after burns (area under the curve [AUC] > 0.9) and generalized to trauma (n&#x2009;=&#x2009;158; AUC 0.81) and intensive care unit COVID-19 (n&#x2009;=&#x2009;103; AUC 0.75), providing information orthogonal to conventional biomarkers and severity scores. Cytomorphology corroborated transcriptomic immaturity, with ~2-fold higher band neutrophils and larger neutrophil size in a fatal case. Computational drug-reversal analysis highlighted galectin-1 inhibition as a candidate modulator of mortality-associated neutrophil programs. Together, our findings suggest that immature neutrophils represent a shared immune feature across severe burns and other forms of critical illness.

Humans

Pulmonary artery catheters or central venous catheters for cardiac surgery: the PUMA Pilot randomised clinical trial.

INTRODUCTION: Pulmonary artery catheters are used widely in cardiac surgery despite observed associations with worse outcomes and guidelines that recommend against their routine use. No adequately powered randomised trials are available. METHODS: The PUMA Pilot was a multicentre, randomised, parallel assignment, open-label, pilot and feasibility trial conducted at three tertiary cardiac surgery centres. Eligible patients were adults undergoing coronary artery bypass grafting, aortic valve replacement or surgery on the aortic root or ascending aorta with or without aortic valve replacement, with a predicted surgical mortality of <&#x2009;2%. Patients were allocated randomly to receive a pulmonary artery catheter or a central venous catheter inserted immediately before surgery. The primary feasibility outcome was protocol compliance, defined as receiving the assigned intervention without crossover. Secondary feasibility outcomes were eligibility rate; recruitment proportion and rate; data completeness; and rate of clinician refusal. RESULTS: We screened 480 patients and 206 (43%) were eligible; 150/203 (74%) approached provided informed consent. Three of 206 (1%) eligible patients were not included due to clinician refusal. Of 149 patients who were randomised, 76 were assigned to the pulmonary artery catheter group and 73 to the central venous catheter group. For the primary feasibility outcome, 147 patients (99%) received the allocated intervention. Data were complete for 144 (97%) patients. Median (IQR [range]) days alive and at home at 30&#x2009;days was 23.7 (21.9-24.7 [7.0-26.0]) in the pulmonary artery catheter group and 22.9 (20.8-23.9 [8.6-25.8]) in the central venous catheter group. Acute kidney injury occurred in 26/76 (34%) patients in the pulmonary artery catheter group and 14/73 (19%) in the central venous catheter group. DISCUSSION: A randomised trial of pulmonary artery catheters compared with central venous catheters in low-risk cardiac surgery is feasible. Such a trial would address significant practice variability and inform international guidelines.

Humans