European Journal of Medical Research最新文献

Background: Timely administration of antibiotics is critical in the management of infectious diseases, particularly in preventing progression to sepsis. Despite the urgency, the appropriate timing of antibiotic treatment, especially in non-septic infections, remains unclear. This study aimed to assess the association between antibiotic timing and progression to sepsis among patients admitted to the Emergency Department (ED) for suspected infection.

Methods: A retrospective cohort study utilized data from three tertiary-care hospital EDs between January 2021 and June 2023. Adult patients hospitalized for clinical infection were included. The primary outcome was sepsis development, while secondary outcomes included hospital mortality, Intensive Care Unit (ICU) admission, ICU length of stay (LOS), and hospital LOS. The main exposure was the duration from ED arrival to initial antibiotic administration. Multivariable logistic and negative binomial regression were employed to adjust for confounders and assess associations.

Results: The study included 1279 infected adult patients, with 20.5% developing sepsis and 10.3% admitted to the ICU, resulting in 3.8% in-hospital deaths. The median time from ED arrival to initial antibiotic administration was 123 min (interquartile range(IQR), 79-241 min). Although per-hour delays in antibiotic administration showed association with sepsis development (Adjusted Odds Ratio(aOR) (95% CI) 1.071(1.044-1.099); P < 0.001), the primary threshold analysis demonstrated that significant associations with sepsis (aOR (95% CI), 3.468 (2.131-5.623); P < 0.001), in-hospital mortality (aOR 2.487, 95% CI 1.083-5.440; P = 0.026), adverse clinical outcomes, and prolonged LOS emerged only when delays exceeded 12 h. These findings were also confirmed by sensitivity analyses.

Conclusions: These hypothesis-generating findings suggest that, in non-severe infections, delays within 12 h might not be associated with significantly increased risks, potentially allowing time for diagnostic clarification without apparent harm. However, due to the observational nature of the study and potential biases, prospective studies are required to confirm these associations.

Introduction: Gallstone disease (GSD) is a common hepatobiliary disorder influenced by bile composition, biliary drainage, and gallbladder motility. Emerging evidence suggests that oral microbiota may contribute to GSD development, but its role remains unclear. This study explores salivary microbiome alterations in GSD patients and their potential clinical relevance.

Methods: This study enrolled 58 GSD patients and 10 age-matched healthy controls. Salivary microbiome profiles were characterized using high-resolution 16S rRNA amplicon sequencing. All participants underwent comprehensive clinical evaluations including physical examinations, oral health assessments, anthropometric measurements, and fasting venous blood sampling for serum biochemical analysis. A multi-dimensional approach was applied to investigate host-microbiome interactions and their potential role in GSD pathogenesis.

Results: Comparative analysis revealed significant microbial divergence between GSD patients and healthy controls, characterized by increased α-diversity indices and distinct β-diversity clustering. The linear discriminant analysis effect size (LEfSe) analysis identified 65 differentially abundant taxonomic features across multiple phylogenetic levels, including 7 phyla, 9 classes, 11 orders, 16 families, and 22 genera, representing 550 operational taxonomic units (OTUs). Notably, Veillonella, Neisseria, Prevotella, and Lachnoanaerobaculum were markedly enriched in the GSD cohort. The developed eXtreme Gradient Boosting (XGBoost) diagnostic model demonstrated exceptional discriminatory capacity, achieving a mean AUC of 0.994 under rigorous fivefold cross-validation. Redundancy analysis (RDA) and Spearman correlation analysis showed strong associations between microbial community structure and key biochemical markers, including chenodeoxycholic acid (CDCA) and alkaline phosphatase (ALP). Functional prediction using PICRUSt2 indicated substantial metabolic pathway alterations in GSD patients, particularly enhanced activity in energy production, amino acid metabolism, and secondary metabolite biosynthesis.

Conclusions: Salivary microbiome dysbiosis in GSD patients demonstrated significant associations with disrupted bile acid homeostasis, suggesting a potential role of the oral microbiota in modulating lithogenic processes. The markedly altered microbial signatures may contribute to GSD pathogenesis, while the XGBoost-based diagnostic model shows considerable promise as a noninvasive tool for GSD detection.

Purpose: To characterize spectrum-dependent changes in Scheimpflug tomographic parameters across normal, keratoconus suspect, and eyes with keratoconus classified using the modified Rabinowitz-McDonnell index.

Methods: This retrospective comparative study included 115 eyes of 115 patients evaluated at a tertiary ophthalmology clinic. Based on the modified Rabinowitz-McDonnell index, eyes were categorized into control (n = 37), keratoconus suspect (n = 51), and keratoconus (n = 27) groups. All eyes underwent Scheimpflug tomography. Anterior and posterior keratometry values, corneal thickness parameters, corneal volume, anterior chamber depth, and pupil diameter were analyzed.

Results: Anterior and posterior corneal curvature parameters increased progressively from control group to keratoconus suspect group and were highest in eyes with keratoconus (all p < 0.001). While anterior keratometric parameters and posterior corneal curvature differed significantly between control and keratoconus suspect groups, pachymetric measurements remained comparable, with significant thinning observed only in the keratoconus group (all p < 0.001). Corneal volume was higher in keratoconus suspect group compared with both control and keratoconus groups (p = 0.001). Anterior chamber depth was greater in keratoconus group, while pupil diameter was smaller in keratoconus suspect group (both p < 0.01).

Conclusion: When keratoconus is classified using central keratometry, Scheimpflug tomography demonstrates a clear, stage-dependent pattern of corneal change. Curvature-related alterations precede measurable thinning, highlighting that curvature-based classification remains clinically relevant and that tomographic parameters can enhance disease characterization across the keratoconus spectrum.

Background: The management of refractory pleural effusion presents a significant clinical challenge. This study aims to compare the outcomes of thoracoscopic talc pleurodesis (TP) and indwelling pleural catheter (IPC) insertion, focusing on survival, complications, and healthcare utilization, while accounting for baseline performance status.

Methods: We conducted a prospective cohort study in 2024 at a single tertiary care center, enrolling 101 patients with refractory pleural effusion. Patients were allocated to either the IPC group (n = 72, 71.3%) or the TP group (n = 29, 28.7%). Primary outcomes included overall survival, length of hospital stay, and total treatment duration. Secondary outcomes were pleurodesis success rate, effusion recurrence, and procedure-related complications. Multivariate analysis was performed to adjust for confounders including age, ECOG performance status, and etiology.

Results: The IPC group had a significantly shorter median hospital stay (1 day vs. 7 days; p < 0.001). Unadjusted survival was significantly lower in the IPC group compared to the TP group at 12 months (13.3% vs. 62.1%; p < 0.001). However, after adjusting for ECOG performance status and age in a multivariate Cox regression, the treatment modality was no longer an independent predictor of mortality (HR 0.78, 95% CI 0.41-1.48; p = 0.45), whereas ECOG score remained a strong predictor (HR 1.65, 95% CI 1.32-2.06; p < 0.001). TP achieved a 100% pleurodesis success rate, compared to 25.4% for IPC (p < 0.001). IPC patients reported less chest pain (13.9% vs. 48.3%; p < 0.001) and bleeding (1.4% vs. 20.7%; p = 0.002).

Conclusion: A significant trade-off exists between the two procedures. IPC is associated with shorter hospitalization and fewer acute complications, while TP offers definitive effusion control. The observed survival difference in the TP group appears to be driven by the selection of fitter patients with better performance status for the more invasive procedure, rather than a direct therapeutic benefit of talc. Treatment decisions must be individualized, weighing patient prognosis and performance status.

Objective: Ankylosing spondylitis (AS) is an inflammatory rheumatic disease, in which an imbalance between loss and formation of bone can lead to ligamentous calcification or osteoporosis. Patients with severe spinal deformities are typically treated with long-segment pedicle screw (PS) internal fixation after bone resection; however, issues with the operation, such as fracture and screw loosening or pulling out, might arise. For patients with low bone quality, the cortical bone trajectory (CBT) has been suggested and developed.

Methods: In order to cure AS, this study set out to look at the biomechanical reactions to PS and CBT fixation. Preoperative and postoperative three-dimensional spine models were reconstructed. A finite element analysis was performed to simulate the motion of the spine under six conditions: flexion, extension, left lateral bending, right lateral bending, left axial rotation, and right axial rotation. The analysis model predicted the stiffness, T12-S1 range of motion (ROM), and Von Mises stress of the vertebra, screw-rod systems, and ligaments.

Results: Axial stiffness was greater in the PS than in the CBT model, while the PS model performed better than the CBT model in terms of bending stiffness, except for the PS model under extension conditions. Under the conditions of bending, extension, and left and right lateral bending, the stress borne by the screws and rods in the PS model was greater than that in the CBT model; whereas, under the conditions of left and right rotation, the stress borne by the CBT model was greater than that in the PS model. The stress was concentrated at the bone resection level. Calcified ligaments experience significant stress during spinal movement. After implantation of the internal fixation, the stress values of the anterior longitudinal ligament, posterior longitudinal ligament, interspinous ligament, and supraspinous ligament decreased, whereas the stress values of some intervertebral ligaments increased.

Conclusion: Under conditions of flexion, extension, and left and right lateral bending, the PS technique provided better biomechanical strength. Whereas, under conditions of left and right rotation, the CBT technique provided better biomechanical strength. Overall, compared to CBT, the current PS technique was sufficiently effective in maintaining spinal fusion stability after bone resection for AS.

Background: The long-term functional prognosis after ischemic stroke (IS) plays a crucial role in rehabilitation planning, yet it remains challenging to predict in clinical practice. Existing prognostic models primarily focus on short-term outcomes and lack integration of multidimensional determinants. Although elevated serum globulin levels have been associated with acute neuroinflammation and short-term disability, their prognostic significance for 1-year functional outcomes within a comprehensive biopsychosocial framework has not yet been established. To address these gaps, this study aimed to develop and validate a multidimensional prognostic model that integrates serum globulin as a key inflammatory biomarker into the International Classification of Functioning, Disability and Health (ICF) framework of the World Health Organization (WHO), with the objective of predicting 1-year functional outcome in patients with acute ischemic stroke (AIS).

Methods: This prospective study consecutively enrolled 1,562 AIS patients at a Grade A tertiary hospital from 2021 to 2023; after data cleaning and screening, 1,356 cases were included for analysis. Baseline data were collected within 1 week of hospital admission. The study cohort was randomly divided into a training set (70%, n = 949) for model development and a validation set (30%, n = 407) for internal validation. The primary outcome was the patients' functional status assessed using the modified Rankin Scale (mRS), 1-year post-admission. Predictors significant (p < 0.05) in univariate analysis within the training set were entered into backward stepwise multivariable logistic regression. The performance of the model was comprehensively evaluated using the area under the curve (AUC), Hosmer-Lemeshow test, calibration curve, and decision curve analysis (DCA).

Results: Multivariable analysis identified six independent predictors (all p < 0.05): age, occupational status, BI, serum globulin, number of stroke episodes and NIHSS. A nomogram incorporating these predictors demonstrated excellent discrimination in both training (AUC = 0.90, 95% CI 0.88-0.93) and validation sets (AUC = 0.85, 95% CI 0.80-0.89). Calibration was good, with predicted probabilities (training: 22.23%; validation: 21.72%) closely matching the observed incidence of 22.20%, nonsignificant Hosmer-Lemeshow test results (p > 0.05), and well-aligned calibration curves. DCA confirmed the model's superior net benefit over "treat-all" and "treat-none" strategies across clinically relevant high-risk thresholds (20-80%) in both training and validation cohorts.

Conclusions: This study successfully integrated serum globulin into the ICF framework and constructed a prognostic model for the 1-year prognosis after AIS. It enables early identification of high-risk individuals and personalized rehabilitation strategies to improve long-term recovery.

Purpose: This study aimed to comparatively evaluate the therapeutic effects of Autologous Cytokine-Rich Serum (ACRS) and Platelet-Rich Plasma (PRP) in a rat model of endometriosis, focusing on inflammation, angiogenesis, and myofibroblast activity.

Methods: A total of 36 adult female Wistar Albino rats were randomly assigned to six groups: healthy control, ACRS-only, PRP-only, endometriosis (EM), EM + ACRS, and EM + PRP. Endometriosis, modeled as lesion formation on the peritoneal wall, was surgically induced in the relevant groups. ACRS and PRP were prepared from autologous blood and administered intraovarianly and intraperitoneally. Lesions were excised for histopathological and immunohistochemical analysis of TNF-α, IL-6 (inflammation), VEGFA (angiogenesis), and α-SMA (fibrosis).

Results: Histopathological scores decreased in both EM + ACRS and EM + PRP groups compared to the EM group. ACRS showed stronger anti-inflammatory effects, with lower TNF-α and IL-6 expression. However, ACRS-treated tissues also exhibited elevated VEGFA and α-SMA expression, suggesting increased angiogenesis and stromal activity.

Conclusions: Both ACRS and PRP showed therapeutic effects. ACRS more effectively suppressed inflammation but may promote lesion stabilization through enhanced angiogenesis and fibrotic remodeling. These findings highlight the complex biological activity of ACRS, which requires further investigation before clinical translation.

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) has emerged as the leading cause of liver dysfunction and poses a significant risk for progression to cirrhosis. In this study, we aimed to compare the ability of various metabolic indices and identify those most effective for the prediction of MAFLD.

Methods: This cross-sectional study included 1471 patients (69.6% MAFLD) between 2011 and 2024. Specific metabolic indices were calculated. The associations between indices and MAFLD were analyzed via logistic regression analysis and restricted cubic splines. The prediction ability of the indices was evaluated via receiver operating characteristic (ROC) analysis in different subgroups.

Results: Triglyceride glucose (TyG) index, homeostatic model assessment for insulin resistance (HOMA-IR), and estimated glucose disposal rate (eGDR) had the strongest associations with MAFLD (final adjusted ORs for TyG = 3.60, HOMA-IR = 3.35, eGDR = 2.97 per unit change). According to the ROC curve analysis, TyG index and hepatic steatosis index (HSI) had the highest area under the curve (AUC) for the prediction of MAFLD in females (AUC = 0.832) and males (AUC = 0.848), respectively. TyG also performed the best in lean/normal-weight and overweight/obesity individuals, with AUCs of 0.890 and 0.787, respectively. TyG in those ≥ 65 years old (AUC = 0.844) and eGDR in those < 65 years old (AUC = 0.843) had the highest prediction performance for MAFLD.

Conclusion: Insulin resistance markers, including TyG, HOMA-IR, and eGDR, had the strongest associations with MAFLD. For predicting MAFLD, TyG had the highest performance across all subgroups, except for males and those < 65 years, where HSI and eGDR performed better, respectively.

Background: Colorectal cancer (CRC) persists as one of the most lethal malignancies worldwide, with therapeutic resistance representing a significant obstacle in clinical management. Ferroptosis, a form of programmed cell death triggered by iron accumulation and lipid peroxidation, has recently emerged as a promising target for cancer therapy. Although low-density lipoprotein receptor-related protein 8 (LRP8) has been implicated in oncogenic processes across cancer types, its involvement in CRC progression and ferroptosis regulation has not been fully elucidated.

Methods: This study utilized an integrative multi-omics approach, incorporating transcriptomic profiling across the colorectal carcinogenesis spectrum (normal mucosa, adenoma, carcinoma; n = 5 each) and proteomic analysis via 4D-DIA mass spectrometry. LRP8 expression patterns were examined in 40 paired CRC and adjacent normal tissues and a tissue microarray comprising 94 cases. Functional investigations were conducted in CRC cell lines following LRP8 knockdown or overexpression. Xenograft models were employed for in vivo validation. Mechanistic insights were gained through co-immunoprecipitation, redox assays, and transmission electron microscopy.

Results: Transcriptomic data revealed a stepwise increase in LRP8 expression during CRC development. Clinical analyses demonstrated that elevated LRP8 levels correlated significantly with advanced tumour stage, lymphatic metastasis, and poorer patient prognosis. Functional assays indicated that LRP8 enhances oncogenic behaviors by interacting with SLC3A2. Reintroducing SLC3A2 in LRP8-depleted cells restored glutathione peroxidase 4 (GPX4) expression and mitigated oxidative stress, thereby rescuing ferroptosis resistance. In vivo, silencing LRP8 inhibited tumour growth and induced ferroptosis-associated alterations, including disrupted iron homeostasis and increased lipid peroxidation.

Conclusion: LRP8 facilitates CRC progression by antagonizing ferroptosis via modulation of the SLC3A2/GPX4 signalling axis. These findings highlight LRP8 as a previously unrecognized regulator of ferroptotic vulnerability and a potential therapeutic target in CRC.

Background: Bronchial challenge testing with methacholine was applied to evaluate and quantify bronchial hyperresponsiveness (BHR) in asthma patients. We aimed to compare the clinical effectiveness between methacholine chloride and methacholine for methacholine challenge testing (MCT) in clinical practice, and investigate the adverse events associated with methacholine chloride.

Methods: Patients who received methacholine and inhaled methacholine chloride for MCT were included in this retrospective study. All participants completed pulmonary function tests and MCT between January 2022 and February 2024. The provocative dose of methacholine that results in a 20% fall in FEV₁ (PD20-FEV₁) was used as quantitative measure of bronchial hyperresponsiveness. The primary outcome of the study was the proportion of positive MCT results and the degree of BHR, while the secondary outcome was the incidence rate of respiratory adverse events during methacholine chloride administration.

Results: A total of 17,352 participants were included. In patients with bronchial symptoms, those administrated methacholine chloride for MCT demonstrated a significantly higher percentage of positive results compared with those administrated conventional methacholine (36.7% vs. 30.8%, P < 0.001). Moreover, PD20-FEV₁ values were significantly lower in methacholine chloride group than methacholine group (P < 0.001). Chest tightness was the most prevalent adverse symptom affecting 30.8% of patients who received methacholine chloride, followed by cough at 27.2%. No serious adverse events were reported in these patients.

Conclusions: The data indicated that methacholine chloride yielded a higher positive test rate than methacholine in MCT. Given that only mild adverse symptoms of chest tightness and cough were observed, with no serious adverse events reported, it represents a safe and effective alternative for clinical BHR assessment.