Significant Increase In Mortality Research Articles

Tendência da taxa de mortalidade por sepse em Minas Gerais entre 2010 e 2023: um estudo ecológico

Sepsis is a critical condition with high mortality, responsible for approximately 11 million deaths annually worldwide and 20% of deaths in Brazil. Between 2010 and 2019, Brazil recorded over 1 million cases and around 463,000 deaths due to sepsis, with the highest mortality in the Southeast region. This ecological study analyzed the age-standardized mortality rate for sepsis in Minas Gerais from 2010 to 2023, using data from the Mortality Information System (SIM) and the Brazilian Institute of Geography and Statistics (IBGE). Prais-Winsten linear regression was applied to identify trends, and the correlation between the age-standardized mortality rate for sepsis (TPMS) and the Social Development Index (SDI) was investigated. Results showed a significant increase in sepsis mortality, with the rate rising from 9.16 in 2010 to 17.98 in 2023, reflecting an Annual Percentage Variation (APV) of 12.86%. The analysis revealed a growing trend with an R² of 0.9600. The positive correlation between TPMS and SDI indicates that regions with higher social development may have higher mortality rates due to better diagnostic capabilities, rather than worse health conditions. The study highlights the urgent need for targeted interventions, such as awareness programs and improvements in sepsis management. Public health strategies focused on prevention, early diagnosis, and effective treatment are essential to mitigate the impact of sepsis and improve clinical outcomes in the region.

ThP7.2 - Nonoperative versus Operative Management in Traumatic Liver Injuries: A Prospective LiPTA Multicentre Study

Abstract Aims The liver is the most injured abdominal organ, with subsequent significant morbidity and mortality. Over the last 30-years liver trauma management has changed, with an increase in nonoperative versus operative approaches. However, contemporary UK data on how liver trauma is managed is limited. Methods This prospective, multicentre audit was conducted through the National Trauma Research and Innovation Collaborative at 18 participating major trauma centres and units across the UK between 01/01/2021-01/10/2021. Differences in demographics, physiology, injury mechanisms, complications, length of stay, and 30-day mortality were compared between patients undergoing definitive nonoperative, including interventional radiology, or operative management. Univariable tests were used to compare data where appropriate with adjusted odds ratios of 30-day mortality used to assess definitive management via a multivariable model. Results Of 266 patients, 76.69% underwent nonoperative management. Operative patients were significantly younger, median age 29 (IQR 20-41) vs. 34 (IQR 23-52) p=0.0146, sustained more penetrating compared to blunt injuries (62.90% vs. 9.80%, p<0.0001), had more active bleeding on CT (32.65% vs. 5.97%, p<0.0001), required massive transfusions (27.42% vs. 8.33%, p=0.0001), sustained more inpatient complications (29.03% vs. 1.96%, p<0.001) and more physiologically unstable on admission. Operative compared to nonoperative management resulted in a significant 20-fold increase in 30-day mortality, (aOR 20.21, 95%CI 3.28-124.43, p=0.001). Conclusions These findings highlight the current approach to UK liver trauma management. Patients undergoing operative management have significantly greater morbidity and mortality yet may represent the severest of liver injures. Where appropriate nonoperative management should be used following liver trauma to reduce this.

Temporal Trends in Takotsubo Syndrome: Results From the International Takotsubo Registry

BackgroundThe perception of takotsubo syndrome (TTS) has evolved significantly over the years, primarily driven by increased recognition of acute complications and mortality. ObjectivesThis study aimed to explore temporal trends in demographic patterns, risk factors, clinical presentations, and outcomes in patients with TTS. MethodsPatients diagnosed with TTS between 2004 and 2021 were enrolled from the InterTAK (International Takotsubo) registry. To assess temporal trends, patients were divided into 6 groups, each corresponding to a 3-year interval within the study period. ResultsOverall, 3,957 patients were included in the study. There was a significant demographic transition, with the proportion of male patients rising from 10% to 15% (P = 0.003). Although apical TTS remained the most common form, the diagnosis of midventricular TTS increased from 18% to 28% (P = 0.018). The prevalence of physical triggers increased from 39% to 58% over the years (P < 0.001). There was a significant increase in 60-day mortality over the years (P < 0.001). However, a landmark analysis excluding patients who died within the first 60 days showed no differences in 1-year mortality (P = 0.150). ConclusionsThis study of temporal trends in TTS highlights a transition in patients demographic with a growing prevalence among men, increasing recognition of midventricular TTS type, and increased short-term mortality and rates of cardiogenic shock in recent years. This transition aligns with the rising prevalence of physical triggers, as expression of increased recognition of TTS in association with acute comorbidities.

776. THREE-FIELD LYMPHADENECTOMY IN ESOPHAGEAL CANCER: EXPERIENCE OF A PORTUGUESE TERTIARY CENTER

Abstract Background The American Joint Committee for Cancer (AJCC) and the Japanese Esophagus Society (JES) differ in the N classification for esophageal cancer, with the former considering the presence of disease in the supraclavicular lymph nodes as M1, and the latter classifying it as loco-regional disease in thoracic esophageal tumors. Patients who would be excluded from a curative intent treatment strategy by the AJCC classification may be candidates for surgery with lymphadenectomy of nodal groups 101 and 104 (JES). Our goal is to understand the impact of three-field lymphadenectomy on morbidity, loco-regional control and overall survival in patients with esophageal cancer. Methods A retrospective cohort study was conducted using data from a prospective database from a single center, which included all consecutive patients undergoing esophagectomy for cancer with either two-field total thoracic lymphadenectomy or three-field lymphadenectomy, between January 2019 and December 2023. Three-field lymphadenectomy was performed for clinical supraclavicular and recurrent nerve nodal involvement and for proximal third tumors. We assessed the morbidity and mortality of both types of surgery, and loco-regional and distant recurrence and overall survival for both groups. Results Of the 279 esophagectomies for cancer, 137 were included for analysis. The median age was 65 years, with 84% males. 58,4% had squamous cell carcinoma and 41,6% adenocarcinoma. 34.3% of the patients had a 3-field lymphadenectomy, 27,7% of these for supraclavicular N+ and 34% for recurrent nerve N+. Conclusion In this large single-center cohort, patients with significant lymph node involvement, treated with esophagectomy and three-field lymphadenectomy, demonstrated comparable loco-regional control and overall survival to more favorable cases, with no statistically significant increase in morbidity and mortality.

Israeli Acute Paralysis Virus Is an Emerging Pathogen Contributing to Brood Disease of Apis cerana

Larval mortality is the primary symptom of diseased Apis cerana colonies, often attributed to sacbrood virus (SBV) and Melissococcus plutonius. However, the impact of other common honeybee viruses is frequently overlooked, and their pathogenicity to A. cerana remains poorly understood. To investigate the causes of the increasing disease incidence in A. cerana brood, we conducted an epidemiological survey, collecting 70 samples from 19 sites across nine provinces in China. Furthermore, we examined the pathogenicity of Israeli acute paralysis virus (IAPV) in A. cerana brood through artificial inoculation experiments. Our results demonstrate that, besides SBV and M. plutonius, the infection rate and viral load of IAPV in diseased brood are significantly high. Brood artificially inoculated with high concentrations of IAPV exhibited a significant increase in mortality and displayed clinical symptoms similar to those observed in naturally infected colonies. Moreover, a limited resistance to IAPV was observed in A. cerana brood, with some individuals able to restrict viral proliferation. Our study highlights the previously unrecognized pathogenicity of IAPV to A. cerana brood, demonstrating that IAPV poses a significant threat similar to SBV and M. plutonius. We emphasize that IAPV should be recognized as an emerging pathogen causing brood disease in A. cerana and managed accordingly in beekeeping practices.

Characteristics, predictors and outcomes of early postoperative cerebral infarction on computed tomography in spontaneous intracerebral hemorrhage

Early postoperative cerebral infarction (ePCI) is a serious complication of spontaneous intracerebral hemorrhage (SICH). Yet, no study has specifically focused on ePCI among SICH patients. Our study aims to investigate the characteristics, predictors, and outcomes of ePCI observed on computed tomography (CT) within 72 h after surgery in patients with supratentorial SICH. Data from a single-center SICH study conducted from May 2015 to September 2022 were retrospectively analyzed. We described the characteristics of ePCI. Predictors were identified through logistic regression analysis, and the impact of ePCI on six-month mortality was examined using a Cox regression model. Subgroup analyses and the “E-value” approach assessed the robustness of the association between ePCI and mortality. A retrospective analysis of 637 out of 3938 SICH patients found that 71 cases (11.1%) developed ePCI. The majority of ePCI cases occurred on the bleeding side (40/71, 56.3%) and affected the middle cerebral artery (MCA) territory (45/71, 63.4%). Multivariable analysis showed that the Glasgow Coma Scale (GCS) score (odds ratio (OR), 0.62; 95% CI, 0.48–0.8; p < 0.001), bleeding volume (per 100 ml) (OR, 1.17; 95% CI, 1.03–1.32; p = 0.016), hematoma volume (per 10 ml) (OR, 1.14; 95%CI, 1.02–1.28; p = 0.023) and bilateral brain hernia (OR, 6.48; 95%CI, 1.71–24.48; p = 0.006) independently predicted ePCI occurrence. ePCI was significantly associated with increased mortality (adjusted hazard ratio (HR), 3.6; 95% CI, 2.2—5.88; p < 0.001). Subgroup analysis and E-value analysis (3.82—6.66) confirmed the stability of the association. ePCI is a common complication of SICH and can be predicted by low GCS score, significant bleeding, large hematoma volume, and brain hernia. Given its significant increase in mortality, ePCI should be explored in future studies.

Serum Homocysteine Levels and All-Cause and Cause-Specific Mortality in Korean Adult Men: A Cohort Study.

Hyperhomocysteinemia can increase the risk of cardiovascular disease (CVD), cancer, and neurological disorders; however, hypohomocysteinemia is generally not considered harmful. This study aimed to evaluate the relationship between all levels of homocysteine, both low and high homocysteine levels, and the risk of all-cause and cause-specific mortality in adult Korean men. Adult Korean men (n = 221,356) were categorized into quintiles based on their homocysteine levels. The primary endpoints were all-cause, CVD, cancer, and dementia mortality. Hazard ratios were calculated using Cox proportional hazards models, and the dose-response relationship between homocysteine levels and mortality risk was further explored using restricted cubic spline models. Compared with the reference category (Q2, 8.8-9.9 µmol/L), there was a significant increase in all-cause mortality associated with both low and high levels after multivariable adjustment (Pinteraction = 0.002). Additionally, in spline regression, a U-shaped association between homocysteine levels and all-cause and CVD mortality was observed (inflection point = 9.1 µmol/L). This association was not observed in the vitamin supplementation subgroup. Among Korean adult men, both low and high homocysteine levels increased the risk of all-cause and CVD mortality, indicating a U-shaped relationship. However, this relationship was not statistically significant with vitamin supplementation, suggesting a potential protective role for vitamins.

Efficacy of Prophylactic Cranial Irradiation in Early to Mid-stage Small Cell Lung Cancer Patients in the Era of Magnetic Resonance Imaging

BackgroundRecent advancements in magnetic resonance imaging (MRI) for staging have highlighted the critical question of the need for prophylactic cranial irradiation (PCI) in managing early to mid-stage small cell lung cancer (SCLC). This study assesses the impact of PCI on overall survival (OS) and intracranial control among patients with stage I-IIB SCLC. MethodsData from 148 stage I-IIB SCLC patients treated with thoracic radiation therapy (TRT) at two centers were examined. Patients were categorized based on PCI administration: 63 received PCI, while 85 did not. All underwent pretreatment MRI, achieving at least a partial response to therapy. A 1:1 propensity score matching analysis corrected for potential biases. ResultsPropensity scores were generated to 116 patients, considering patient demographics, disease progression, and treatment methods. Death was included as a competing risk. The 3-year brain metastases (BM) occurrence rate was significantly higher in patients who did not receive PCI (30.0%) compared to those who did (14.8%), however, the difference was not statistically significant (No PCI vs. PCI, hazard ratio [HR]: 2.08, 95% CI [0.93-4.55], P = .07). No significant effect of PCI on OS was observed [PCI vs. No PCI, HR: 0.80, 95% CI (0.45-1.43), P = .45]. A subgroup analysis of stage IIB patients showed a significant increase in BM risk and mortality for those not receiving PCI (No PCI vs. PCI, BM risk HR: 5.85, 95% CI: 1.83-18.87, P = .003; mortality HR: 2.78, 95% CI: 1.14-6.67, P = .02), with less pronounced effects in stages I-IIA. ConclusionWith modern MRI-based screening, PCI may markedly benefit stage IIB SCLC patients by reducing BM and improving OS after initial sensitive treatment. This benefit does not appear to extend to stage I-IIA patients.

Two Decades of CABG in the UK: A Propensity Matched Analysis of Outcomes by Conduit Choice.

Background/Objectives: Grafting of LIMA to LAD has long been considered the gold-standard conduit choice for patients undergoing CABG. Despite this, the LSV remains the most used conduit by volume and some patients may not receive even a single arterial conduit. However, the outcomes in this group are not frequently explored. This study, therefore, compares in-hospital outcomes of patients who underwent CABG without any arterial conduits to those who received at least one arterial conduit. Methods: Retrospective propensity-matched database analysis of consecutive patients undergoing CABG in the UK between 1996 and 2019 using data from the National Adult Cardiac Surgery Audit. Results: 335,144 patients underwent CABG, with 6% receiving venous conduits only; matched outcomes are reported for 39,812 patients. In both unmatched and matched groups, we found a significant increase in mortality with the use of veins only (matched mortality 5.3% vs. 3.8%, p < 0.001) with estimated treatment effect for mortality OR 1.43, p < 0.001 (95% CI: 1.31-1.57). We also identified greater rates of post-operative dialysis, IABP insertion, and length of hospital stay in this group. Conclusions: We identified a significant increase in in-hospital mortality with the use of veins only compared to using at least one arterial graft to the LAD. While a single arterial graft should be prioritised wherever possible, venous revascularisation retains a critical role for specific patients. We must, therefore, continue to conduct research addressing the mechanisms underlying and propagating vein graft disease in order better to optimise outcomes for this niche patient group after CABG.

Redefining urine output thresholds for acute kidney injury criteria in critically Ill patients: a derivation and validation study

IntroductionThe current definition of acute kidney injury (AKI) includes increased serum creatinine (sCr) concentration and decreased urinary output (UO). Recent studies suggest that the standard UO threshold of 0.5 ml/kg/h may be suboptimal. This study aimed to develop and validate a novel UO-based AKI classification system that improves mortality prediction and patient stratification.MethodsData were obtained from the MIMIC-IV and eICU databases. The development process included (1) evaluating UO as a continuous variable over 3-, 6-, 12-, and 24-h periods; (2) identifying 3 optimal UO cutoff points for each time window (stages 1, 2, and 3); (3) comparing sensitivity and specificity to develop a unified staging system; (4) assessing average versus persistent reduced UO hourly; (5) comparing the new UO-AKI system to the KDIGO UO-AKI system; (6) integrating sCr criteria with both systems and comparing them; and (7) validating the new classification with an independent cohort. In all these steps, the outcome was hospital mortality. Another analyzed outcome was 90-day mortality. The analyses included ROC curve analysis, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and logistic and Cox regression analyses.ResultsFrom the MIMIC-IV database, 35,845 patients were included in the development cohort. After comparing the sensitivity and specificity of 12 different lowest UO thresholds across four time frames, 3 cutoff points were selected to compose the proposed UO-AKI classification: stage 1 (0.2–0.3 mL/kg/h), stage 2 (0.1–0.2 mL/kg/h), and stage 3 (< 0.1 mL/kg/h) over 6 h. The proposed classification had better discrimination when the average was used than when the persistent method was used. The adjusted odds ratio demonstrated a significant stepwise increase in hospital mortality with advancing UO-AKI stage. The proposed classification combined or not with the sCr criterion outperformed the KDIGO criteria in terms of predictive accuracy—AUC-ROC 0.75 (0.74–0.76) vs. 0.69 (0.68–0.70); NRI: 25.4% (95% CI: 23.3–27.6); and IDI: 4.0% (95% CI: 3.6–4.5). External validation with the eICU database confirmed the superior performance of the new classification system.ConclusionThe proposed UO-AKI classification enhances mortality prediction and patient stratification in critically ill patients, offering a more accurate and practical approach than the current KDIGO criteria.

Clot lysis time and thrombin generation in patients undergoing transcatheter aortic valve implantation.

Aortic valve stenosis (AS) is the most prevalent valvular heart disease and is associated with a significant increase in mortality. AS has been shown to be linked with numerous coagulation system abnormalities, including increased fibrin deposition on the stenotic aortic valves. Transcatheter aortic valve implantation (TAVI) is the primary treatment method for patients at high surgical risk. The aim of the study was to assess the impact of treating severe AS with TAVI on thrombin generation and clot lysis time (CLT). We studied 135 symptomatic AS patients recommended for TAVI by the local Heart Team. All measurements were performed before and 5-7 days after TAVI. Alongside clinical assessment and echocardiographic analysis, we assessed clot lysis time (CLT) and thrombin generation parameters, including lag time, peak thrombin generation, time to peak thrombin generation (ttPeak), and endogenous thrombin potential (ETP). 70 patients were included in the final analysis. After TAVI, there was a significant 9% reduction in CLT despite a 12% increase in fibrinogen concentration. We observed significant increase in lag time and ttPeak (20% and 12%, respectively), and 13% decrease in peak thrombin concentration compared to pre-procedural levels. Multivariable linear regression analysis demonstrated that baseline CLT and C-reactive protein (CRP) levels were independent predictors of significant reduction in mean aortic gradient, defined as TAVI procedure success. CLT and peak thrombin concentration decreased, while Lag time and ttPeak increased significantly after TAVI. Multivariable linear regression analysis demonstrated CLT and CRP levels as independent predictors of achieving a reduction in mean aortic gradient, defining TAVI procedure success.

Safety assessment of high doses of vaporized oxalic acid on honey bee worker health and queen quality

IntroductionThe honey bee ectoparasitic mite, Varroa destructor, is one of the main causes of honey bee colony loss worldwide. Synthetic acaricides are the most commonly used strategy for varroa control, however, resistance to these acaricides has emerged. Consequently, the use of organic acids for varroa control is gaining more interest among beekeepers. For example, oxalic acid (OA) is a natural compound that has been shown to be an effective acaricide against varroa mites, however, the potential toxicity of OA to adult bees and queens is poorly understood. The objective of the study was to evaluate the toxicity of incremental doses of vaporized OA on honey bee workers and queens.MethodsWe exposed 32 colonies to incremental doses (0, 5, 10 or 20 g per colony) of vaporized OA once per week over four consecutive weeks and we monitored the acute and long-term toxicity. We investigated the short-term effects of OA administration by evaluating adult bee mortality, brood production, and population size. Next, we evaluated the long-term effects of OA application on both worker bees and queens. Regarding workers, we investigated their ability to rear new queens. As for queens, we measured acceptance, performance, and sperm quality.ResultsWe found that colonies treated with 20 g OA (20 times the label dose) had a statistically significant increase in worker bee mortality, with a non-significant, 23% decrease in brood relative to controls. No significant differences were observed in queen performance nor sperm quality.DiscussionWe found that repeated application of vaporized OA, at up to 20 times the label dose, had no significant short-term nor long-term, negative effects on colony or queen health, with the exception of a short-term increase in adult bee mortality in the 20 g OA-treated group. The results of this study support the safety of higher-than-label doses of OA for honey bee colonies. The observed increase in adult bee mortality in the 20 g OA dose group in this study suggests that OA doses should be maintained below 20 g per brood chamber.

The influence of air masses on human mortality in the contiguous United States.

Temperature-related mortality is the leading cause of weather-related deaths in the United States. Herein, we explore the effect of air masses (AMs) - a relatively novel and holistic measure of environmental conditions - on human mortality across 61 cities in the United States. Geographic and seasonal differences in the effects of each AM on deseasonalized and detrended anomalous lagged mortality are examined using simple descriptive statistics, one-way analyses of variance, relative risks of excess mortality, and regression-based artificial neural network (ANN) models. Results show that AMs are significantly related to anomalous mortality in most US cities, and in most seasons. Of note, two of the three cool AMs (Cool and Dry-Cool) each show a strong, but delayed mortality response in all seasons, with peak mortality 2 to 4days after they occur, with the Dry-Cool AM having nearly a 15% increased risk of excess mortality. Humid-Warm (HW) air masses are associated with increases in deaths in all seasons 0 to 1days after they occur. In most seasons, these near-term mortality increases are offset by reduced mortality for 1-2weeks afterwards; however, in summer, no such reduction is noted. The Warm and Dry-Warm AMs show slightly longer periods of increased mortality, albeit slightly less intensely as compared with HW, but with a similar lag structure by season. Meanwhile, the most seasonally consistent results are with transitional weather, whereby passing cold fronts are associated with a significant decrease in mortality 1day after they occur, while warm fronts are associated with significant increases in mortality at that same lag time. Finally, ANN modeling reveals that AM-mortality relationships gleaned from a combined meta-analysis can actually lead to more skillful modeling of these relationships than models trained on some individual cities, especially in the cities where such relationships might be masked due to low average daily mortality.

Demographic and Prognostic Factors of the Columnar Cell Variant of Papillary Thyroid Carcinoma: A National Cancer Database Study.

Objective The columnar cell variant of papillary thyroid carcinoma (PTC-CC) is a rare, malignant tumor of the thyroid gland. This study uses the National Cancer Database (NCDB) to analyze demographic and prognostic factors affecting the overall survival rates of PTC-CC. Methods From 2004 to 2020, 7,079 patients diagnosed with columnar cell papillary thyroid carcinoma were identified in the NCDB. Patient demographics were reviewed based on categories listed in the NCDB participant user file data dictionary. Kaplan-Meier curves, log-rank tests, and multivariable Cox hazard regression models were used to analyze the significance of demographic and prognostic factors on overall survival rates of PTC-CC. Results Multivariate analysis demonstrated each five-year increment in age was associated with a 30% increase in mortality (hazard ratio (HR) = 1.30, 95% confidence interval (CI): 1.25-1.36, P < 0.001). Charlson-Deyo scores displayed similar incremental increases, such that patients with a score ≥ 3 had a 154% increase in mortality risk relative to a score of 0 (HR = 2.54; 95% CI: 1.75-3.68, P < 0.001). Black individuals had a 70% increase in mortality compared to White individuals (HR = 1.70, 95% CI: 1.25-2.30, P < 0.001), while all Other races had the highest 10-year survival rate of 92.7%. Females had a significant 37% decrease in mortality compared to males (HR = 0.63, 95% CI: 0.54-0.73, P < 0.001). Patients in the lowest income quartiles were found to have a significant increase in mortality compared to the highest income group (HR = 0.54; 95% CI: 0.41-0.71, P < 0.001). Survival rates were negatively correlated with NCDB Analytic Staging increases. Conclusion In general, age, sex, race, education, income, comorbidities, and cancer staging were found to be predictive factors of overall survival rates of PTC-CC. However, insurance status and education levels did not result in significant differences.

Anesthetic key points in a patient with a terminal ileum neuroendocrine tumor and a rare carcinoid left heart disease presented for non-cardiac surgery: case report

BackgroundCarcinoid tumors are rare neuroendocrine malignancies presenting in an increasing number in our center. The incidence of carcinoid tumors is approximatively between 2.5 and 5 cases per 100,000 people of whom about 50% develop carcinoid syndrome. Once the carcinoid syndrome has developed, a carcinoid cardiomyopathy can occur. Carcinoid heart disease (CaHD) remains a serious and rare complication associated with a significant increase in morbidity and mortality. Although carcinoid tumors have been known and studied for several years, there are still scarce data on the anesthetic management and the peri operative period.Case presentationWe describe a case of a Caucasian 44-year-old woman with an unusual presentation of left CaHD with an ileal neuroendocrine tumor and liver metastases. Our preoperative somatostatin administration protocol, limit the cardiac damage. The maintenance of stable hemodynamics, the use of balanced anesthetic technique, all along with a good understanding of the pathology, played a major role in the successful management of anesthesia. This case report allows us to introduce our decision algorithm for the management of this type of pathology in our tertiary hospital, Cliniques Universitaires Saint-Luc.ConclusionDespite the paucity of data, anesthetic management of patients with carcinoid tumor can be safely performed with effective hemodynamic monitoring and a good understanding of the pathophysiology. Knowledge and application of a clear institutional algorithm for octreotide administration and multidisciplinary consultation at a referral center are essential for the management of these patients.

Enhancing Trauma Care: A Machine Learning Approach with XGBoost for Predicting Urgent Hemorrhage Interventions Using NTDB Data.

Trauma is a leading cause of death worldwide, with many incidents resulting in hemorrhage before the patient reaches the hospital. Despite advances in trauma care, the majority of deaths occur within the first three hours of hospital admission, offering a very limited window for effective intervention. Unfortunately, a significant increase in mortality from hemorrhagic trauma is primarily due to delays in hemorrhage control. Therefore, we propose a machine learning model to predict the need for urgent hemorrhage intervention. This study developed and validated an XGBoost-based machine learning model using data from the National Trauma Data Bank (NTDB) from 2017 to 2019. It focuses on demographic and clinical data from the initial hours following trauma for model training and validation, aiming to predict whether trauma patients require urgent hemorrhage intervention. The XGBoost model demonstrated superior performance across multiple datasets, achieving an AUROC of 0.872 on the training set, 0.869 on the internal validation set, and 0.875 on the external validation set. The model also showed high sensitivity (77.8% on the external validation set) and specificity (82.1% on the external validation set), with an accuracy exceeding 81% across all datasets, highlighting its high reliability for clinical applications. Our study shows that the XGBoost model effectively predicts urgent hemorrhage interventions using data from the National Trauma Data Bank (NTDB). It outperforms other machine learning algorithms in accuracy and robustness across various datasets. These results highlight machine learning's potential to improve emergency responses and decision-making in trauma care.

Comprehensive analysis of aberrantly methylated differentially expressed genes and validation of CDC6 in melanoma

BackgroundSkin Cutaneous Melanoma (SKCM) is a highly aggressive malignant tumor with a significant increase in mortality upon metastasis. The molecular mechanisms driving melanoma progression remain largely unclear. Recent studies have highlighted the importance of epigenetic alterations, especially DNA methylation, in melanoma development. This study aims to identify and analyze methylation-regulated differentially expressed genes (MeDEGs) in genome-wide profiles between primary and metastatic melanoma.MethodsGene expression profiling datasets GSE8401 and gene methylation profiling datasets GSE86355 were collected from the GEO database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were systematically identified. Integration of DEGs and DMGs yielded a set of MeDEGs, which subsequently underwent functional enrichment analysis. The protein-protein interaction (PPI) network was constructed using STRING and visualized using Cytoscape software. Survival analysis was used to select prognostic hub genes. In addition, 37 SKCM and 37 normal skin tissues from the First Affiliated Hospital of Soochow University (FAHSU) were collected for immunohistochemical (IHC) staining and evaluation. Furthermore, DNA methylation patterns of CDC6 were analyzed. To validate these findings, SKCM cell cultures were utilized to elucidate the expression and behavioral characteristics of CDC6. Additionally, gene set enrichment analysis (GSEA) and immune infiltration analysis were conducted for CDC6.ResultsIn our study, we discovered 120 hypomethylated-upregulated genes and 212 hypermethylated-downregulated genes. The hypomethylated-upregulated genes were notably associated with biological processes such as spindle assembly checkpoint signaling, mitotic spindle assembly, and negative regulation of mitotic metaphase/anaphase transition. Our pathway analysis revealed significant enrichment in pathways related to dilated cardiomyopathy, amino sugar metabolism, progesterone-mediated oocyte maturation, and chemical carcinogenesis. Conversely, hypermethylated-downregulated genes were found to be enriched in processes like epidermis development, keratinocyte differentiation, and skin development. Additionally, pathway analysis highlighted associations with estrogen signaling, Staphylococcus aureus infection, axon guidance, and arachidonic acid metabolism. Following the establishment of PPI networks and survival analysis, we identified 11 prognostic hub genes: CCNA2, CDC6, CDCA3, CKS2, DTL, HJURP, KRT5, KRT14, KRT15, KRT16, and NEK2. Notably, among the 11 hub genes, our findings indicate that CDC6 plays a pivotal role in enhancing the proliferation, migration, and invasion capabilities of melanoma cells in vitro.ConclusionsOur comprehensive genomic analyses reveal that genes with aberrant methylation exhibit differential expression during the transition from primary to metastatic melanoma. The identified genes, especially CDC6, which plays a crucial role in enhancing melanoma cell proliferation, migration, and invasion, provide valuable insights into potential methylation-based biomarkers. These findings could contribute significantly to advancing precision medicine in SKCM.

Identification of ASMTL-AS1 and LINC02604 lncRNAs as novel biomarkers for diagnosis of colorectal cancer

PurposeColorectal cancer is one of the major leading causes of death worldwide, and available treatments for advanced colorectal cancer are not successful. Therefore, early detection of colorectal cancer is essential to improve patient survival, and biomarkers are potential tools to achieve this goal. Considering the key role of lncRNAs in cancers, the aim of this study is to identify lncRNAs involved in colorectal cancer as new potential prognosis biomarkers for CRC.MethodsIn this observational study, gene expression data obtained from the TCGA database were analyzed, Identification of differentially expressed mRNAs, miRNAs, and lncRNAs was performed, and ceRNA network was drawn. Also, survival analysis of patients was performed in order to identify potential biomarkers related to the diagnosis and prognosis of colon cancer. After confirming the results using the GSE39582 dataset, the expression of target lncRNAs in colorectal tumor tissues was also investigated to confirm the bioinformatic data.ResultsAnalysis of the TCGA data showed that the expression of three lncRNAs—SNHG7, ASMTL-AS1, and LINC02604—that had the highest interaction with other miRNAs and mRNAs identified based on the ceRNA network was increased in colorectal cancer. Also, based on the ceRNA network, three microRNAs, hsa-let-7d-5p, hsa-mir-92a-3p, and hsa-mir-423-5p, and eight mRNAs, including CPA4, MSI2, RRM2, IGF2BP1, ONECUT2, HMGA1, SOX4, and SRM, were associated with all three mentioned lncRNAs, the expression of microRNAs was decreased and the expression of mRNAs was increased. By enrichment analysis, it was found that the target lncRNAs are involved in the processes of cell proliferation, apoptosis, and metastasis, indicating their importance in the development and malignancy of colorectal cancer. Furthermore, Kaplan–Meier analysis showed a significant increase in mortality in patients with higher expression levels of these lncRNAs. Analysis of the GSE39582 dataset, and real-time RT-PCR analysis, confirmed our bioinformatic results. Also, ROC analysis showed that SNHG7 was a relatively good promising biomarker (AUC = 0.73, p value = 0.02), while ASMTL-AS1 (AUC = 0.92, p value < 0.0001) and LINC02604 (AUC = 1.00, p value < 0.0001) emerged as excellent diagnostic biomarkers in colorectal cancer.ConclusionIt seems that increased expression of lncRNAs ASMTL-AS1 and LINC02604 can serve as molecular biomarkers for CRC, possibly through the sponge hsa-let-7d-5p, hsa-mir-92a-3p, and hsa-mir-423 5p, which increases target mRNAs, which are effective in the carcinogenesis process.

Effects of α-olefin sulfonate (AOS) on Tubifex tubifex: toxicodynamic-toxicokinetic inferences from the general unified threshold (GUTS) model, biomarker responses and molecular docking predictions.

We investigated the potential ecological risks and harm to aquatic organisms posed by anionic surfactants such as α-olefin sulfonate (AOS), which are commonly found in industrial and consumer products, including detergents. This study assessed acute (96-h) and subchronic (14-day) responses using antioxidant activity, protein levels, and histopathological changes in Tubifex tubifex exposed to different AOS concentrations (10% of the LC50, 20% of the LC50, and a control). Molecular docking was used to investigate the potential interactions between the key stress biomarker enzymes (superoxide dismutase, catalase, and cytochrome c oxidase) of Tubifex tubifex. Acute AOS exposure showed a concentration-dependent decrease in survival, and the general unified threshold (GUTS) model revealed that survivorship is linked to individual response patterns rather than random (stochastic) fluctuations. The GUTS model also revealed dose-dependent toxicity patterns in Tubifex tubifex exposed to α-olefin sulfonate (AOS), with adaptive mechanisms at lower concentrations but significant increases in mortality beyond a certain threshold, emphasizing the role of the AOS concentration in shaping its toxicological impact. Exposure to AOS disrupted antioxidant activity, inducing oxidative stress, with GST and GPx showing positive associations with surfactant concentration and increased lipid peroxidation (elevated MDA levels); moreover, AOS exposure decreased protein concentration, signifying disturbances in vital cellular processes. Histopathological examinations revealed various tissue-level alterations, including cellular vacuolation, cytoplasmic swelling, inflammation, necrosis, and apoptosis. Molecular docking analysis demonstrated interactions between AOS and enzymes (-catalase, superoxide dismutase, and cytochrome c oxidase) in Tubifex tubifex, including hydrophobic and hydrogen bond interactions, with the potential to disrupt enzyme structures and activities, leading to cellular process disruptions, oxidative stress, and tissue damage. According to the species sensitivity distribution (SSD), the difference in toxicity between Tilapia melanopleura (higher sensitivity) and Daphnia magna (low sensitivity) to AOS suggests distinct toxicokinetic and toxicodynamic mechanisms attributable to more complex physiology in Tilapia and efficient detoxification in Daphnia due to its smaller size.

Aprotinin in high-risk isolated coronary artery bypass graft patients: a 3-year propensity matched study

BackgroundAprotinin, a serine protease inhibitor, has been used variably in cardiac surgery amidst ongoing debates about its safety following several previous studies. This study assesses the outcomes of aprotinin in high-risk isolated Coronary Artery Bypass Graft (iCABG) patients.MethodsThe study retrospectively analysed a cohort of 1026 iCABG patients, including 51 patients who underwent aprotinin treatment. Logistic regression powered score matching was employed to compare aprotinin patients with a control group, in a propensity-matched cohort of 96 patients. The primary outcome measured was in-hospital death, with secondary outcomes including renal dysfunction, stroke, myocardial infarction, re-exploration for bleeding or tamponade, and postoperative stay durations.ResultsThe aprotinin cohort had high-risk preoperative patients with significantly higher EUROSCORE II values, 7.5 (± 4.2), compared to 3.9 (± 2.5) in control group. However, aprotinin group showed no statistically significant increase (p-value: 0.44) in hospital mortality with OR 2.5 [95% CI 0.51, 12.3]. Major secondary outcome rates of renal replacement therapy and postoperative stroke compared to the control group were also statistically insignificant between the two groups.ConclusionThis study suggests that aprotinin may be safely used in a select group of high-risk iCABG patients. The reintroduction of aprotinin under specific conditions reflects its potential benefits in managing bleeding in high-risk surgeries, but also underscores the complexity of its risk-benefit profile in such critical care settings. Nonetheless, it highlights the importance of carefully selecting patients and conducting additional research, including larger and more controlled studies to fully comprehend the potential risks and benefits of aprotinin.