Tag: pubmed

Br J Anaesth. 2025 Oct 10:S0007-0912(25)00602-6. doi: 10.1016/j.bja.2025.08.036. Online ahead of print.

ABSTRACT

BACKGROUND: This meta-analysis is the first to compare tracheal intubation conditions and haemodynamic responses produced by various types and doses of neuromuscular blocking agents (NMBAs) in paediatric anaesthesia while also exploring factors associated with variability in outcomes.

METHODS: Randomised controlled and controlled clinical trials involving healthy paediatric participants (0-12 yr) were included. Trials compared intubation conditions using various NMBA interventions or NMBA-free settings under direct laryngoscopy. Outcomes included odds ratios (ORs) for excellent and acceptable intubation conditions, and mean differences for MAP and HR. Bayesian network, pairwise, and cumulative meta-analyses, along with meta-regression, assessed NMBA effectiveness and covariate effects.

RESULTS: Data from 105 trials (8008 participants) were analysed. Suxamethonium ≥1.50 mg kg^-1 and rocuronium ≥0.90 mg kg^-1 provided similar intubation conditions, though not consistently within 60 s. Other NMBAs were, on average, slower and less effective. Opioids decreased MAP and HR but did not improve intubation conditions when combined with suxamethonium ≥1.00 mg kg^-1 or rocuronium ≥0.90 mg kg^-1. Non depolarising NMBAs enhanced excellent (OR: 2.97 [1.82-5.10]) and acceptable intubation conditions (OR: 2.29 [1.14-4.39]) more in younger children (1.64 [1.08-2.20] yr) than in older ones (5.53 [4.04-7.01] yr). Intubation without NMBAs was most difficult in neonates and infants, with conditions improving until about age 4 yr. Beyond this, the difference in intubation quality between groups with and without NMBAs increased with age, indicating a greater benefit of using NMBAs in older children. Values are mean (95% credible interval).

CONCLUSIONS: We present a meta-analytical approach to synthesise and consolidate evidence from previous research and demonstrate how neuromuscular blocking agent type and dose, intubation timing, age, and induction drugs affect the safety and efficacy of paediatric airway management. Low-to-moderate confidence can be assigned to the recommendations from this meta-analysis.

SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42018097146).

PMID:41076411 | DOI:10.1016/j.bja.2025.08.036

Clin Genitourin Cancer. 2025 Sep 11:102432. doi: 10.1016/j.clgc.2025.102432. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the risk of contralateral lymph node involvement (LNI) and the feasibility of safely performing unilateral pelvic lymph node dissection (PLND) in unfavorable-intermediate and high-risk prostate cancer (PCa) patients with cN0 status on preoperative ⁶⁸Ga-PSMA PET/CT, tumor involvement in single lobe, or dominant lobe involvement with worse tumor characteristics on biopsy.

MATERIAL AND METHODS: In this retrospective multicenter study were analyzed 768 patients who underwent RP and bilateral extended-PLND. Patients with cN0 status on PSMA PET/CT and PI-RADS ≥ 3 lesions on multiparametric magnetic resonance imaging(mpMRI) were included. Tumor lobe (single/dominant-prostatic lobe) involvement and LNI status were recorded for all patients. The dominant lobe was determined based on higher ISUP grade group(GG), number and percentage of more positive cores, and more advanced features on MRI, respectively. LNI status was analyzed by tumor side and location. Statistical analysis included univariate and multivariate models to evaluate predictors of contralateral LNI.

RESULTS: LNI was observed in 96(12.5%) of 768 patients, with 61(7.9%) having ipsilateral LNI and 35(4.6%) contralateral LNI with or without ipsilateral LNI. Patients with contralateral LNI had higher preoperative PSA, more frequent EAU high-risk classification, larger-index lesion diameter, higher ISUP GG on both the dominant and nondominant side, and a higher rate of positive percentages in the nondominant side (all P values < .05). Multivariate analysis identified preoperative PSA (HR 1.028, 95% Cl 1.001-1.057, P = .044), ISUP GG 2 (HR 4.325,95% Cl-1.620-14.374,P = .007) and ≥ ISUP-GG 3 (HR 14.004, 95% Cl 3.025-54.773, P < .001) on the nondominant side as independent predictors for contralateral LNI. The ROC-derived AUC for predicting contralateral LNI was 0.873, indicating good predictive accuracy.

CONCLUSION: In cases where preoperative ⁶⁸Ga-PSMA PET/CT indicates a negative LN status, contralateral PLND may not be necessary in intermediate-risk patients with negative biopsy or ISUP GG 1 tumor on the nondominant side.

PMID:41076397 | DOI:10.1016/j.clgc.2025.102432

Chin J Traumatol. 2025 Sep 17:S1008-1275(25)00114-2. doi: 10.1016/j.cjtee.2025.03.002. Online ahead of print.

ABSTRACT

PURPOSE: Hidden blood loss (HBL) during the perioperative period significantly impacts postoperative recovery and complications, yet it is frequently disregarded. This study aimed to investigate the effects of tip-apex distance (TAD) and calcar-referenced tip-apex distance (calTAD) on HBL in the treatment of intertrochanteric fractures utilizing proximal femoral nail antirotation (PFNA). The study also seeks to evaluate the possible decrease in HBL subsequent to PFNA treatment by optimizing nail positioning.

METHOD: A historical cohort study was conducted from January 2020 to December 2022. Patients diagnosed with unilateral acute closed femoral intertrochanteric fracture and who underwent PFNA internal fixation surgery met the inclusion criteria, and were grouped according to the value of calTAD and TAD. The participants were divided into low TAD group (TAD<20 mm) and high TAD group (TAD≥20 mm); low calTAD group (calTAD<7.625 mm) and high calTAD group (calTAD≥7.625 mm), respectively. The primary outcome measures were intraoperative blood loss (including HBL, overt blood loss, and total blood loss). Continuous data were analyzed using an independent sample t-test or Mann-Whitney U test, and categorical data were analyzed using the Pearson Chi-square test. Univariate analysis was used to evaluate the association between various indicators and perioperative HBL. A stepwise multiple linear regression analysis model was used to determine the independent factors affecting perioperative HBL. A p value less than 0.05 was considered statistically significant.

RESULTS: A total of 131 patients were initially included, of which 80 were assigned to the calTAD group (with 61 in the high calTAD group and 19 in the low calTAD group), and 80 were assigned to the TAD group (with 34 in the high TAD group and 46 in the low TAD group). The average HBL for the low TAD group was 772.85 mL, whereas for the high TAD group it was 919.68 mL (p>0.05). The average HBL for the low calTAD group was 611.42 mL, whereas for the high calTAD group it was 904.97 mL (p<0.05). Subsequent analysis revealed that the patient’s height, preoperative hemoglobin levels, changes in hemoglobin and hematocrit levels from pre- to post-surgery, and calTAD are independent risk factors influencing HBL.

CONCLUSION: In summary, our investigation revealed a significant correlation between the positioning of nails in PFNA and HBL during the perioperative period. By optimizing the placement of the cephalic nail, specifically by ensuring a calTAD of less than 7.625 mm, a significant decrease in HBL can be attained. Additionally, we identified that height, preoperative hemoglobin, differences in preoperative and postoperative hemoglobin and hematocrit, and the positioning of the cephalic nail were independent risk factors for HBL.

PMID:41076394 | DOI:10.1016/j.cjtee.2025.03.002

J Natl Cancer Inst. 2025 Oct 11:djaf289. doi: 10.1093/jnci/djaf289. Online ahead of print.

ABSTRACT

BACKGROUND: Tumor-infiltrating lymphocytes (TILs), assessed by visual examination (VE), are prognostic and predictive in early-stage triple-negative breast cancer (TNBC). Computational assessment (CA) may provide a complementary approach. We evaluated the prognostic value of TILs by VE and CA.

METHODS: TBCRC 030 was a randomized phase II trial enrolling patients with BRCA1/2-proficient stage I-III TNBC to receive preoperative cisplatin or paclitaxel. The primary endpoint was pathologic response at surgery. TILs were visually scored on digitized pre-treatment biopsies per International TILs Working Group recommendations. CA used the 4D QPOR platform to generate TILs, immune heterogeneity index (IHI), and a combined immune/cell cycle biomarker (CmbI). Predictive performance for residual cancer burden (RCB) 0/1 was assessed using ROC curves and odds ratios (ORs) with 95% CIs; all statistical tests were two-sided.

RESULTS: Of 139 response-evaluable patients, 121 had matched VE and CA data (59 cisplatin, 62 paclitaxel). Median VE TILs were higher in responders (40.0% vs. 10.0%, p = .002) and predicted response (OR 1.86, 95% CI 1.24-2.87, AUC 0.69, 95% CI 0.57-0.80). CA CmbI differed by response group and predicted RCB 0/1 (OR 3.20, 1.05-11.07; AUC 0.62, 0.51-0.73). CA TILs and IHI were not predictive. VE TILs and CA CmbI predicted response to paclitaxel (OR 2.91, 1.56-6.14; OR 9.17, 2.01-66.39, respectively), but not to cisplatin.

CONCLUSION: VE TILs and CA CmbI were each associated with response to NAC in TNBC in the overall cohort and the paclitaxel arm. CA CmbI did not outperform visual assessment. Further validation is needed before clinical implementation of computational approaches.

PMID:41075163 | DOI:10.1093/jnci/djaf289

Bioinformatics. 2025 Oct 11:btaf570. doi: 10.1093/bioinformatics/btaf570. Online ahead of print.

ABSTRACT

MOTIVATION: Differential expression analysis plays a vital role in omics research enabling precise identification of features that associate with different phenotypes. This process is critical for uncovering biological differences between conditions, such as disease versus healthy states. In proteomics, several statistical methods have been used, ranging from simple t-tests to more advanced methods like DEqMS, limma and ROTS. However, a flexible method for reproducibility-optimized statistics tailored for clinical omics data has been lacking.

RESULTS: In this study, we developed LimROTS, a hybrid method that integrates a linear regression model and the empirical Bayes approach with the Reproducibility-Optimized Statistics, to create a novel moderated ranking statistic, for robust and flexible analysis of proteomics data. We validated its performance using twenty-one proteomics gold standard spike-in datasets with different protein mixtures, MS instruments, and techniques for benchmarking. This hybrid approach improves accuracy and reproducibility of complex proteomics data, making LimROTS a powerful tool for high-dimensional omics data analysis.

AVAILABILITY: LimROTS has been implemented as an R/Bioconductor package, available at https://bioconductor.org/packages/LimROTS/. Additionally, the code used in this study is available in GitHub repository https://github.com/AliYoussef96/LimROTSmanuscript.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:41075160 | DOI:10.1093/bioinformatics/btaf570

Bioinformatics. 2025 Oct 11:btaf561. doi: 10.1093/bioinformatics/btaf561. Online ahead of print.

ABSTRACT

MOTIVATION: Understanding the genetic basis of drug-induced toxicity is crucial for drug development. In-silico analysis of toxicogenomics datasets facilitates early detection of toxicity biomarkers. However, existing tools struggle with the complex interdependencies among hierarchically structured variables, leading to inaccurate biomarker identification. To address this limitation, we developed a Hierarchical Linear Model (HLM) and implemented it in the R package ToxAssay, offering extensive functionality for comprehensive toxicity assessment.

RESULTS: ToxAssay outperforms existing methods by improving biomarker detection and computational efficiency. Applied to glutathione depletion-induced toxicity, it prioritized 71 key genes and identified 26 core genes with high discriminative accuracy (AUC = 0.97) and strong cross-correlation (Pearson’s r = 0.88) with external datasets. Additionally, our advance outcome pathway (AOP) analysis algorithm uncovered disease outcomes linked to glutathione depletion. These findings provide precise insights into the molecular mechanisms driving drug-induced toxicity.

AVAILABILITY: ToxAssay is available as an open-source R package at https://github.com/Fun-Gene/toxassay.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:41075158 | DOI:10.1093/bioinformatics/btaf561

Clin Rheumatol. 2025 Oct 11. doi: 10.1007/s10067-025-07736-x. Online ahead of print.

ABSTRACT

INTRODUCTION/OBJECTIVE: Respiratory muscle function may be impaired in axial spondyloarthritis (axSpA) due to mechanical limitations of the thoracic spine and chest wall. However, the extent of respiratory muscle weakness and its clinical associations remain largely underexplored.

METHODS: This comparative cross-sectional study included 51 patients with radiographic axSpA (r-axSpA) and 52 healthy controls. Maximal inspiratory (PI_max) and expiratory (PE_max) pressures were measured using standardized protocols. Patients with r-axSpA also underwent assessments of pulmonary functions (forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁)), spinal pain, disease activity, spinal mobility, functional status, physical performance, quality of life, anxiety/depression, and fatigue. Subgroup analyses were performed based on the presence of respiratory muscle weakness (< 80% of predicted PI_max and PE_max), and stepwise multiple regression was used to identify clinical predictors of PI_max.

RESULTS: Although the PI_max (mean difference: – 8.6% [95% CI: – 21.7% to 4.6%]) and PE_max (mean difference: – 4.6% [95% CI: – 16.7% to 7.5%]) were lower in the r-axSpA group, the differences were not statistically significant (p > 0.05). Seventeen patients (33.3% of the total sample) with r-axSpA exhibited inspiratory muscle weakness. This subgroup demonstrated significantly poorer FVC, spinal pain at rest, spinal mobility, and quality of life (p < 0.05). Regression analysis revealed that pain at rest (β = – 0.317, p = 0.013) and FVC (β = 0.296, p = 0.022) independently predicted 19.2% of the variance in PI_max.

CONCLUSION: Although respiratory muscle strength was mostly preserved in r-axSpA, a substantial subgroup exhibited inspiratory muscle weakness associated with adverse clinical outcomes. Identifying these patients may guide tailored interventions for optimal care.

KEY POINTS: A substantial proportion of patients with radiographic axSpA demonstrate inspiratory muscle weakness despite preserved average respiratory pressures. Patients with inspiratory muscle weakness exhibit diminished lung volumes, decreased spinal mobility, higher pain levels, and poorer quality of life compared to those without weakness. Inspiratory muscle strength is independently predicted by spinal pain at rest and forced vital capacity.

PMID:41075137 | DOI:10.1007/s10067-025-07736-x

Clin Rheumatol. 2025 Oct 11. doi: 10.1007/s10067-025-07715-2. Online ahead of print.

ABSTRACT

OBJECTIVE: Axial spondyloarthritis (AxSpA) and Behçet’s disease (BD) have clinical and HLA locus overlap and have been grouped under MHC-I-opathy. This study aimed to identify overlapping loci between AxSpA and BD to help elucidate MHC-I-opathy pathogenesis.

METHODS: Association clustering methods, such as OASIS, reduce the multiple-testing burden and are more powerful than single variant analysis for identifying modest genetic effects. Two large publicly available genome-wide association studies (GWAS) of AxSpA (921 cases, 907 controls) and BD (1215 cases and 1278 healthy controls) from Turkiÿe were subjected to OASIS meta-analyses to identify common non-HLA loci. Statistics used to identify significant loci included the novel OASIS locus index (OLI). Expression analysis was performed using GEO datasets, GSE181364 for AxSpA and GSE209567 for BD. STRING network analysis was performed.

RESULTS: GWAS for both diseases had the highest significance at the HLA-I locus. Of the 234 independent modestly significant non-HLA loci, there were 15 loci common to both AxSpA and BD. These included known MHC-I-opathy loci, 1p31.3 for IL23R (P = 5.37 × 10^-6, OLI = 52.7) and 13q14.11 for LACC1 (P = 7.41 × 10^-6, OLI = 65.3). A novel locus identified in this study is 3p21.31 containing CXCR6 (P = 2.46 × 10^-5, OLI = 25.8). The locus 3p22.3 had the highest overall OLI (81.3), and the most significant SNP at this locus (rs2291897; P = 1.82 × 10^-5) is an intronic variant in the gene FBXL2. However, this association was specific for BD only.

CONCLUSION: Several loci containing pathologically relevant genes for MHC-I-opathy were identified here, using a cluster-based approach in AxSpA and BD GWAS, with CXCR6 being a novel target. Key Points • MHC-I-opathy immunopathogenesis is incompletely understood and challenged by risk genes of modest effect. • This meta-analysis identified 15 loci common to both AxSpA and BD that may provide diagnostic and therapeutic targets for MHC-I-opathy. • Major candidate genes for MHC-I-opathy identified here are IL23R, LACC1, and CXCR6. • FBXL2 was associated strongly with BD by OASIS analysis.

PMID:41075136 | DOI:10.1007/s10067-025-07715-2

Med Biol Eng Comput. 2025 Oct 11. doi: 10.1007/s11517-025-03460-5. Online ahead of print.

ABSTRACT

Minimally invasive neurosurgery presents specific challenges due to the limited operative space and complex cranial anatomy, requiring highly precise and safe surgical guidance. Augmented Reality (AR) technology offers the potential to improve surgical accuracy and safety by overlaying critical digital information onto real-world surgical environments. In this study, we present a study that aims to compare four AR visualization methods-2D flat display, smart tablet, head-mounted display (HMD), and 3D autostereoscopic display-in guiding minimally invasive neurosurgical procedures, specifically focusing on ventriculocentesis. The effectiveness of the AR methods was evaluated through comprehensive user studies involving 32 participants (including 11 experienced surgeons), with assessment focused on critical performance metrics including accuracy, completion time, usability, and cognitive workload during simulated surgical procedures. Results demonstrated that 3D visualization methods significantly outperformed traditional 2D approaches in terms of puncture accuracy and angular precision. Specifically, surgeons showed a statistically significant improvement in localization accuracy, with mean error reduced from 2.69 mm to 1.67 mm, and angular deviation from 5.62° to 1.54°. In comparing the two 3D visualization systems, the HMD exhibited superior task completion efficiency, while the 3D autostereoscopic display demonstrated higher usability scores and lower perceived workload ratings. Notably, the 3D systems effectively reduced the performance disparity between novice and experienced practitioners, suggesting their potential to accelerate the learning curve for less experienced users. We conclude that AR holds significant potential to enhance performance and decision-making in minimally invasive neurosurgical guidance.

PMID:41075112 | DOI:10.1007/s11517-025-03460-5

Cancer Causes Control. 2025 Oct 11. doi: 10.1007/s10552-025-02046-8. Online ahead of print.

ABSTRACT

PURPOSE: This study evaluated the feasibility, acceptability, usability, and HPV vaccine completion rate of the Now I Know (NIK) mHealth intervention to promote HPV vaccine completion among minority and low-income young women.

METHODS: This quasi-experimental pilot study recruited 35 women aged 18-26 at two federally supported outpatient clinics in a large city in the Northeastern United States. Participants were allocated to two groups: 24 received the NIK intervention plus usual care and 11 received usual care only. After completing a baseline assessment, intervention group participants launched the NIK mobile app, which entailed HPV vaccine education, self-managed vaccine record & reminder, and Q&A features. Follow-up visits were conducted at 2 and 6 months. Feasibility was assessed through screening, recruitment, fidelity, and retention. Acceptability and usability were evaluated via survey and exit interview. The primary outcome-HPV vaccine 3-dose series completion-was analyzed using descriptive statistics.

RESULTS: This study demonstrated feasibility by reaching the recruitment target (n = 35) and high retention rate (89%). Participants reported the app was acceptable, appreciating reliable information, convenient access, providing a personal touch, and raising awareness. Regarding usability, users found the app easy to navigate, accessible, well organized, and user-friendly. The HPV vaccine completion rate was higher in the intervention group (55%) than in the usual care group (45.5%).

CONCLUSION: Findings showed improved vaccination completion among those using the Now I Know mHealth intervention (compared to usual care), acceptability of the intervention, and feasibility of recruiting, retaining, and delivering the intervention to promote HPV vaccine completion among young women in federally subsidized healthcare settings.

PMID:41075078 | DOI:10.1007/s10552-025-02046-8