European Journal of Medical Research最新文献

Background: NUP98 rearrangements (NUP98-r) are rare but overrepresented mutations in pediatric acute myeloid leukemia (AML) patients. NUP98-r is often associated with chemotherapy resistance and a particularly poor prognosis. Therefore, characterizing pediatric AML with NUP98-r to identify aberrations is critically important.

Methods: Here, we retrospectively analyzed the clinicopathological features, genomic and transcriptomic landscapes, treatments, and outcomes of pediatric patients with AML.

Results: Nine patients with NUP98-r mutations were identified in our cohort of 142 patients. Ten mutated genes were detected in patients with NUP98-r. The frequency of FLT3-ITD mutations differed significantly between the groups harboring NUP98-r and those without NUP98-r (P = 0.035). Unsupervised hierarchical clustering via RNA sequencing data from 21 AML patients revealed that NUP98-r samples clustered together, strongly suggesting a distinct subtype. Compared with that in the non-NUP98-r fusion and no fusion groups, CMAHP expression was significantly upregulated in the NUP98-r samples (P < 0.001 and P = 0.001, respectively). Multivariate Cox regression analyses demonstrated that patients harboring NUP98-r (P < 0.001) and WT1 mutations (P = 0.030) had worse relapse-free survival, and patients harboring NUP98-r (P < 0.008) presented lower overall survival.

Conclusions: These investigations contribute to the understanding of the molecular characteristics, risk stratification, and prognostic evaluation of pediatric AML patients.

Background: Post-extubation dysphagia (PED) emerges as a frequent complication following endotracheal intubation within the intensive care unit (ICU). PED has been strongly linked to adverse outcomes, including aspiration, pneumonia, malnutrition, heightened mortality rates, and prolonged hospitalization, resulting in escalated healthcare expenditures. Nevertheless, the reported incidence of PED varies substantially across the existing body of literature. Therefore, the principal objective of this review was to provide a comprehensive estimate of PED incidence in ICU patients undergoing orotracheal intubation.

Methods: We searched Embase, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science, Technology Journal Database (VIP), and SinoMed databases from inception to August 2023. Two reviewers independently screened studies and extracted data. Subsequently, a random-effects model was employed for meta-statistical analysis utilizing the "meta prop" command within Stata SE version 15.0 to ascertain the incidence of PED. In addition, we performed subgroup analyses and meta-regression to elucidate potential sources of heterogeneity among the included studies.

Results: Of 4144 studies, 30 studies were included in this review. The overall pooled incidence of PED was 36% (95% confidence interval [CI] 29-44%). Subgroup analyses unveiled that the pooled incidence of PED, stratified by assessment time (≤ 3 h, 4-6 h, ≤ 24 h, and ≤ 48 h), was as follows: 31.0% (95% CI 8.0-59.0%), 28% (95% CI 22.0-35.0%), 41% (95% CI 33.0-49.0%), and 49.0% (95% CI 34.0-63.0%), respectively. When sample size was 100 < N ≤ 300, the PED incidence was more close to the overall PED incidence. Meta-regression analysis highlighted that sample size, assessment time and mean intubation time constituted the source of heterogeneity among the included studies.

Conclusion: The incidence of PED was high among ICU patients who underwent orotracheal intubation. ICU professionals should raise awareness about PED. In the meantime, it is important to develop guidelines or consensus on the most appropriate PED assessment time and assessment tools to accurately assess the incidence of PED.

Background: Aortic stenosis (AS) is a prevalent and serious valvular heart disease with a complex etiology involving genetic predispositions, lipid dysregulation, and inflammation. The specific roles of lipid and protein biomarkers in AS development are not fully elucidated. This study aimed to elucidate the causal relationships between lipidome, inflammatory proteins, and AS using Mendelian randomization (MR), identifying potential therapeutic targets.

Methods: Utilizing data from large-scale genome-wide association studies (GWAS) and genome-wide protein quantitative trait loci (pQTL) studies, we conducted MR analyses on 179 plasma lipidome and 91 inflammatory proteins to assess their causal associations with AS. Our approach included Inverse Variance Weighting (IVW), Wald ratio, and robust adjusted profile score (RAPS) analyses to refine these associations. MR-Egger regression was used to address directional horizontal pleiotropy.

Results: Our MR analysis showed that genetically predicted 50 lipids were associated with AS, including 38 as risk factors [(9 Sterol ester, 18 Phosphatidylcholine, 4 Phosphatidylethanolamine, 1 Phosphatidylinositol and 6 Triacylglycerol)] and 12 as protective. Sterol ester (27:1/17:1) emerged as the most significant risk factor with an odds ratio (OR) of 3.11. Additionally, two inflammatory proteins, fibroblast growth factor 19 (FGF19) (OR = 0.830, P = 0.015), and interleukin 6 (IL-6) (OR = 0.729, P = 1.79E-04) were significantly associated with reduced AS risk. However, a two-step MR analysis showed no significant mediated correlations between these proteins and the lipid-AS pathway.

Conclusion: This study reveals complex lipid and protein interactions in AS, identifying potential molecular targets for therapy. These results go beyond traditional lipid profiling and significantly advance our genetic and molecular understanding of AS, highlighting potential pathways for intervention and prevention.

Purpose: For women with locoregionally advanced cervical cancer, the standard of care treatment is the curatively intended chemoradiation therapy (CRT). A relationship between bone marrow (BM) dose-volume histograms (DVHs) and acute hematological toxicity (HT) has been debated recently. Aim of this study was the evaluation of BM dose constraints and HT in a contemporary patient cohort.

Methods: Radiation treatment plans of 31 patients with cervical cancer (FIGO stage IIB-IVB) treated with intensity-modulated radiotherapy and simultaneous chemotherapy were explored retrospective. Pelvic bones (PB) and femoral heads (FH) were contoured and DVHs were correlated with white blood cells (WBC), hemoglobin levels and platelets.

Results: Comparing the absolute blood levels with the dose volumes of both FH and PB the data showed a significant correlation between WBC and the median dose of the FH and the median dose, V_30Gy, V_40Gy and V_50Gy of the PB. A correlation between the toxicity grade of anemia and mean dose, maximum dose and V_5Gy of the PB was found. Counting the highest grade of HT of all three blood levels of each patient, significant correlations were found for the mean and median dose, V_30Gy, V_40Gy and V_50Gy of the PB.

Conclusion: The results show that blood levels may correlate with distinct dosimetric subvolumes of critical bone marrow compartments with a potential impact on therapeutic outcome and treatment-related toxicity. The data presented are in line with the previous findings on the relevance of dosimetric exposure of pelvic bony subvolumes.

Introduction: This study aims to construct a mortality prediction model for patients with non-variceal upper gastrointestinal bleeding (NVUGIB) in the intensive care unit (ICU), employing advanced machine learning algorithms. The goal is to identify high-risk populations early, contributing to a deeper understanding of patients with NVUGIB in the ICU.

Methods: We extracted NVUGIB data from the Medical Information Mart for Intensive Care IV (MIMIC-IV, v.2.2) database spanning from 2008 to 2019. Feature selection was conducted through LASSO regression, followed by training models using 11 machine learning methods. The best model was chosen based on the area under the curve (AUC). Subsequently, Shapley additive explanations (SHAP) was employed to elucidate how each factor influenced the model. Finally, a case was randomly selected, and the model was utilized to predict its mortality, demonstrating the practical application of the developed model.

Results: In total, 2716 patients with NVUGIB were deemed eligible for participation. Following selection, 30 out of a total of 64 clinical parameters collected on day 1 after ICU admission remained associated with prognosis and were utilized for developing machine learning models. Among the 11 constructed models, the Gradient Boosting Decision Tree (GBDT) model demonstrated the best performance, achieving an AUC of 0.853 and an accuracy of 0.839 in the validation cohort. Feature importance analysis highlighted that shock, Glasgow Coma Scale (GCS), renal disease, age, albumin, and alanine aminotransferase (ALP) were the top six features of the GBDT model with the most significant impact. Furthermore, SHAP force analysis illustrated how the constructed model visualized the individualized prediction of death.

Conclusions: Patient data from the MIMIC database were leveraged to develop a robust prognostic model for patients with NVUGIB in the ICU. The analysis using SHAP also assisted clinicians in gaining a deeper understanding of the disease.

Context: Polycystic ovary syndrome (PCOS), a common endocrine disorder in women of reproductive age, is closely associated with chronic low-grade inflammation and metabolic disturbances. In PCOS mice, dietary inulin has been demonstrated to regulate intestinal flora and inflammation. However, the efficacy of dietary inulin in clinical PCOS remains unclear.

Objective: The intestinal flora and related metabolic indexes of obese patients with polycystic ovary syndrome (PCOS) after 3 months of inulin treatment were analyzed.

Setting and design: To analyze the intestinal flora and related metabolic indexes in healthy controls and obese patients with polycystic ovary syndrome after 3 months of inulin treatment.

Results: The results showed that dietary inulin improved sex hormone disorders, reduced BMI and WHR levels in obese women with PCOS. In addition, the inulin intervention reduced plasma TNF-α, IL-1β, IL-6, and MCP-1levels. Inulin intervention increased the abundance of Actinobacteria, Fusobacteria, Lachnospira, and Bifidobacterium, as well as decreased the ratio of F/B and the abundance of proteobacteria, Sutterella, and Enterobacter. Correlation analyses showed a strong relationship among plasma inflammatory factors, sex steroid hormones, and the intestinal flora of patients.

Conclusions: Dietary inulin may improve obese PCOS women disease through the gut flora-inflammation-steroid hormone pathway.

The clinical trial registration number: ChiCTR-IOR-17012281.

Background: Previous studies on PCT for urinary tract infections (UTI) have focused primarily on minors. This study investigated the predictive value of the neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP) level and procalcitonin (PCT) level in adult patients with bacteriuria in IUC.

Methods: This case‒control study included 85 patients with bacteriuria (PB) in the ICU from March 2021 to Jan 2024 based on positive urine culture results and a control group (n = 136) from Jan 2024 to March 2024. Patient data were collected using a hospital information management system. ROC curves of the NLR, CRP and PCT were use to predict the PB.

Results: The AUCs of the NLR, CRP and PCT for the prediction of PB in ICU were 0.711 (95% CI 0.644-0.772), 0.855 (95% CI 0.800-0.900), and 0.884 (95% CI 0.832-0.924), respectively; the optimal thresholds were 8.02, 18.52 mg/L, and 0.215 ng/mL, respectively; the sensitivities were 69.0 (95% CI 56.9-79.5), 90.1 (95% CI 80.7-95.9), and 83.1 (95% CI 72.3-91.0), respectively; and the specificities were 67.6 (95% CI 59.1-75.4), 68.4 (95% CI 59.9-76.1), and 80.9 (95% CI 73.3-87.1), respectively. The negative predictive value (NPV) of CRP is greater than that of PCT. In bacteriuria caused by Candida infections, CRP and PCT have higher sensitivity and NPV.

Conclusions: Combined CRP and PCT testing is more helpful for diagnosing bacteriuria. CRP and PCT have higher sensitivity and NPV in diagnosing bacteriuria caused by Candida infection.

Background: Activation of the IL-33/ST2 axis leads to the production of proinflammatory cytokines and thus to the triggering of osteoclastogenesis, which is why it plays an important role in the immunopathogenesis of periodontitis. The aim of this study was to compare IL-33 levels in serum, plasma, saliva and gingival crevicular fluid (GCF) of subjects with chronic periodontitis (CP) in comparison with the control group (CG).

Methods: This systematic review and meta-analysis followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and was registered in the Open Science Framework (OSF): https://doi.org/10.17605/OSF.IO/YHUWA . Six electronic databases were used for study identification; PubMed, Google Scholar, ScienceDirect, Web of Science, Scopus and Dentistry & Oral Sciences Source from March 10, 2012 to April 30, 2024. The Joanna Briggs Institute (JBI) tool was used to assess the quality of the included cross-sectional articles and clinical trials.

Results: Of the 949 articles identified, 14 were included according to the inclusion and exclusion criteria. The total number of individuals studied in the included investigations was 814 of whom 445 had CP and 369 were healthy. The reported age range was from 20 to 50 years, with a mean age ± standard deviation of 40.29 ± 7.83 years. Four hundred and twenty-six (52%) patients were men and 388 (48%) were women. Meta-analysis revealed that there is an increase in IL-33 levels in plasma, saliva and GCF of subjects with CP compared to CG (p = * < 0.05).

Conclusions: This study found a significant increase in IL-33 levels in different biological samples (plasma, saliva and GCF) of individuals with CP compared to CG, thus IL-33 has potential to be a biomarker in the diagnosis of periodontitis.

Objectives: A correlation exists between lipids and osteoporosis (OP), as well as between lipids and rheumatoid arthritis (RA). However, lipids, the relationship between RA and OP is still unclear. This study mainly investigates the relationship between lipid levels and OP risk in RA patients.

Methods: Retrospective collection of RA patient data from July 2017 to May 2022, encompassing baseline demographics, treatment regimens, laboratory results, and bone mineral density (BMD) measurements. Analyses, stratified by BMD subgroups, were conducted using propensity score matching (PSM) based on age, sex, and baseline duration, and binary logistic regression to examine the interplay between lipoprotein levels and other risk factors. The relationship between continuous variables and OP risk was assessed using restricted cubic spline (RCS), followed by a reanalysis of the correlation between varying lipoprotein levels and different factors, segmented according to RCS-determined cutoffs.

Results: The study included 2673 RA patients. Binary logistic regression revealed significant associations between high-density lipoprotein (HDL), low-density lipoprotein (LDL), and RA-OP (p < 0.01). Specifically, HDL emerged as a protective factor against OP (OR = 0.40, 95% CI 0.250-0.629; p < 0.001), whereas LDL was identified as a risk factor (OR = 1.56, 95% CI 1.290-1.890; p < 0.001). Furthermore, HDL (RCS cutoff point 1.28 mmol/L) showed a negative, linear correlation with RA-related OP, while LDL (RCS cutoff point 2.63 mmol/L) demonstrated a positive, linear correlation.

Conclusions: The levels of HDL and LDL may be indicators of OP occurrence in RA patients.

Tuberculosis is a serious global health burden, resulting in millions of deaths each year. Several circulating cell subsets in the peripheral blood are known to modulate the host immune response to Mycobacterium tuberculosis (Mtb) infection in different ways. However, the characteristics and functions of these subsets to varying stages of tuberculosis infection have not been well elucidated. Peripheral blood immune cells (PBICs) were isolated from healthy donors (HD group), individuals with mild tuberculosis (MI group), and individuals with severe tuberculosis (SE group). CD4+ naive T cells and CD8+ T cells were decreased in the SE and MI groups, while CD14+ monocytes were increased in the SE group. Further analysis revealed increased activated CD4+ T cells, transitional CD8+ T cells, memory-like NK cells, and IGHG3^highTTN^highFCRL5^high B cells were increased in all patients with tuberculosis (SE and MI group). In contrast, Th17 cells, cytotoxic NK cells, and cytotoxic CD4+ T cells were decreased. Moreover, the increase of CD14+CD16+ monocytes correlated with severe tuberculosis, and the GBP5^highRSAD2^high neutrophils were unique to patients with severe tuberculosis. Cellular communication analysis revealed that CD8+ T cells exhibited the highest incoming interaction strength in the SE group. The increased CD8+ T cell incoming interactions are associated with the MHC-I and LCK pathways, with HLA-(A-E)-CD8A, HLA-(A-E)-CD8B, and LCK-(CD8A+CD8B) being ligand-receptor pairs. Patients with tuberculosis, especially severe tuberculosis, have profound changes in peripheral blood immune cell profiles. CD8+ T cells showed the highest incoming interaction strength in patients with severe tuberculosis, with the main signals being MHC-I and LCK pathways.