Category: Statistics

Clin Transl Oncol. 2026 Mar 10. doi: 10.1007/s12094-026-04301-z. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to construct and validate a dedicated prognostic model for patients with RAS-mutant metastatic colorectal cancer (mCRC) using real-world data from two centers and explore the differences in the efficacy of first-line standard chemotherapy regimens in this population to provide an evidence-based foundation for individualized prognostic assessment and the selection of first-line treatment strategies.

METHODS: Clinical, pathological, and follow-up data from 275 patients with RAS-mutant mCRC treated in two hospitals from January 2016 to December 2023 were retrospectively collected. Prognosis-related candidate variables were screened by univariate Cox regression and LASSO regression, and a prognostic model was constructed using a stepwise multivariate Cox proportional hazards model. For variables violating the proportional hazards assumption, a time-dependent Cox model was further used for correction. Model performance was evaluated by the concordance index (C-index), time-dependent receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Leave-one-out cross-validation (LOOCV) was used to test its stability, and the tercile method was adopted for stratified validation to assess the stratification efficiency. In addition, 129 patients receiving first-line standard chemotherapy were selected from the total cohort to form an efficacy analysis cohort. The Kaplan-Meier method and the Cox proportional hazards regression model combined with multivariate adjustment were used to explore the differences in efficacy of different chemotherapy regimens with or without bevacizumab.

RESULTS: The final prognostic model included four independent prognostic factors: lesion resection status, number of metastatic organs, CA19-9 level, and serum ALB concentration. The C-index of the model was 0.730 (95% CI: 0.689-0.771), and the pooled C-index verified by LOOCV was 0.705 (95% CI: 0.662-0.747). Time-dependent ROC analysis at 1, 2, and 3 years revealed that the AUC values of the model were 0.806, 0.781, and 0.772, respectively. The calibration curve had a good fit, and DCA confirmed that the model had clinical net benefit over a wide threshold range. There were significant differences in survival among patients in the high-, medium-, and low-risk groups (P < 0.001), indicating good stratification efficiency of the model. Exploratory efficacy analysis revealed that compared with single two-drug chemotherapy, two-drug chemotherapy combined with bevacizumab significantly prolonged the median progression-free survival (mPFS) of patients (9.61 vs. 6.74 months, P = 0.025), and this benefit remained stable after multivariate adjustment (HR = 0.437; 95% CI: 0.241-0.791; P = 0.006), but there was no significant difference in overall survival (OS) between the two groups. No statistically significant differences were observed in the objective response rate (ORR), PFS, or OS between patients receiving oxaliplatin-based or irinotecan-based two-drug chemotherapy combined with bevacizumab.

CONCLUSION: The prognostic model and the corresponding nomogram constructed in this study can be used to conveniently evaluate the 1- to 3-year survival probability of patients with RAS-mutant mCRC. Exploratory analysis using real-world data revealed that two-drug chemotherapy combined with bevacizumab can significantly prolong the PFS of this population, providing a reference for the selection of first-line treatment regimens for this group. Both oxaliplatin- and irinotecan-based two-drug regimens combined with bevacizumab can be used as options for first-line treatment, and clinical selection can be made comprehensively on the basis of the individual conditions of patients. This study has several limitations, such as its retrospective design, unbalanced sample size in efficacy subgroups, and lack of external validation of the model, and the conclusions need to be further verified by large-sample prospective multicenter studies.

PMID:41806240 | DOI:10.1007/s12094-026-04301-z

Clin Transl Oncol. 2026 Mar 10. doi: 10.1007/s12094-026-04296-7. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Cervical carcinoma, exhibits distinctive hallmarks, including sustained proliferation and replicative immortality. Ki-67 is a well-established marker of cell proliferation, while the presence of telomerase, particularly its catalytic subunit human Telomerase Reverse Transcriptase (hTERT), is associated with the uncontrolled proliferation seen in many cancers.

METHOD: The expression of Ki-67 and the hTERT component of telomerase was investigated in various cervical lesions. Tissue microarray blocks were prepared from a total of 586 paraffin-embedded cervical tissue specimens received at Sultan Qaboos University Hospital and Royal Hospital between January 2010 and December 2018. Immunohistochemistry was performed to assess the expression of both markers.

RESULTS: The results showed that Ki-67 expression increased significantly with the severity of cervical lesions (p < 0.05), with SCC displaying high Ki-67 expression in more than 50% of tumor cells. However, statistical analysis revealed no significant correlation between Ki-67 expression and lesion prognosis. On the other hand, hTERT showed a significantly higher expression in low-grade LSIL (p < 0.05), whereas high-grade squamous intraepithelial lesions and SCC predominantly showed negative hTERT expression. hTERT staining was mainly localized to the nucleus across all cervical lesions, with some cytoplasmic and combined expressions, and it was generally of mild intensity; however, this correlation was not statistically significant. Additionally, the percentage of hTERT-positive cells was mostly below 10% in all lesion types, with no statistically significant differences observed.

CONCLUSION: Our findings suggest that the use of Ki-67 and hTERT component of telomerase combination might not be sufficient to predict the prognosis of cervical lesions. Nonetheless, the observed expression patterns of each biomarker indicate a potential role in early carcinogenesis.

PMID:41806237 | DOI:10.1007/s12094-026-04296-7

Eur J Pediatr. 2026 Mar 10;185(3):171. doi: 10.1007/s00431-026-06828-3.

ABSTRACT

To evaluate whether implementation of a multidisciplinary care pathway was associated with changes in unplanned emergency department (ED) visits in children with musculoskeletal infections, and to assess its impact on readmissions, reoperations, and key process measures. We conducted a single-centre quality-improvement study of children with septic arthritis (SA) or acute osteomyelitis (AO) treated at a tertiary paediatric hospital in Canada. A pathway introduced in September 2021 standardised C-reactive protein (CRP) monitoring, discharge documentation, and coordinated in-person and virtual follow-up. Consecutive post-pathway patients (September 2021-July 2022) were compared with a pre-pathway cohort (June 2018-August 2021). The primary outcome was unplanned ED visits within three months of discharge. Secondary outcomes included readmission, reoperation, and predefined process measures. Analyses used regression models and statistical process control (SPC) p-charts. A total of 122 children were included (77 pre-pathway, 45 post-pathway). Median age was similar between groups (4.0 vs 6.5 years, p = 0.25). Unplanned ED visits decreased from 28.6% to 17.8% (RR 0.62, 95% CI 0.30-1.28; p = 0.18). However, this difference was not statistically significant, and SPC analysis demonstrated common-cause variation. Pathway phase was not independently associated with ED visits after adjustment (OR 1.46, 95% CI 0.53-4.04; p = 0.47). Readmissions and reoperations were unchanged. Several process measures improved, including day-3 CRP measurement (61.0 vs 86.7%; p = 0.003), number of follow-up visits (median 3 vs 5; p < 0.001), and fewer missed appointments (median 1 vs 0; p < 0.001).

LEVEL OF EVIDENCE: Level III (Prospective comparative quality improvement study).

CONCLUSION: Implementation of a multidisciplinary care pathway was associated with improved process reliability and follow-up adherence. Although unplanned ED visits were lower in the post-pathway cohort, this difference did not reach statistical significance. These findings support coordinated, team-based approaches to optimise care processes for paediatric musculoskeletal infections.

WHAT IS KNOWN: • Children with septic arthritis and acute osteomyelitis frequently have unplanned emergency department visits after discharge, despite relatively low readmission and reoperation rates. • Care delivery often varies across the inpatient-outpatient continuum, with inconsistent inflammatory marker monitoring and limited multidisciplinary coordination.

WHAT IS NEW: • Implementation of a multidisciplinary care pathway was associated with improved CRP monitoring, follow-up adherence, and appointment reliability. • Although unplanned ED visits were numerically lower post-pathway, this difference did not reach statistical significance; however, process reliability and continuity of care improved without increases in readmissions or reoperations.

PMID:41806202 | DOI:10.1007/s00431-026-06828-3

J Gastroenterol. 2026 Mar 10. doi: 10.1007/s00535-026-02382-9. Online ahead of print.

ABSTRACT

BACKGROUND: MicroRNAs (miRNAs) enclosed within extracellular vesicles (EVs) have emerged as crucial players in carcinogenesis and are increasingly recognized as potential cancer biomarkers. However, their significance in pancreatic ductal adenocarcinoma (PDAC) and their utility for early detection remain unclear.

METHODS: We utilized microarray analysis to identify the miRNAs highly expressed in PDAC cells compared to immortalized pancreatic ductal cells. Functional studies investigated the effect of miRNA overexpression and inhibition on PDAC cells invasion/migration and associated signaling pathways. Additionally, we examined the transfer of miRNA via EVs and their potential impact on the recipient PDAC cells. Serum samples from 30 healthy individuals, 30 patients with intraductal papillary mucinous neoplasm, and 30 PDAC were analyzed for EV miRNA expression using digital PCR.

RESULTS: MiR-425 emerged as an oncogenic miRNA upregulated in PDAC, suppressing phosphatase and tensin homolog (PTEN) while activating phosphatidylinositol 3-kinase (PI3K)/Akt and epithelial-to-mesenchymal transition (EMT) pathways. Treatment with miR-425-enriched EVs induced EMT in PDAC cells by suppressing PTEN, enhancing invasion and migration. Serum EV miR-425 levels tended to be higher in PDAC patients, particularly in Stage I/II compared to Stage III/IV, although the difference was not statistically significant. Combining EV miR-425 with CA19-9 improved diagnostic performance over CA19-9 alone, achieving a sensitivity 93%, specificity 91%, and AUC of 0.98.

CONCLUSION: Our finding suggested the role of intercellular transfer of EV miR-425 in inducing EMT via PTEN/PI3K/Akt pathway modulation, thereby promoting invasion and migration of PDAC cells. Serum EV miR-425 holds promise as a potential biomarker for early diagnosis of PDAC.

PMID:41806200 | DOI:10.1007/s00535-026-02382-9

Paediatr Anaesth. 2026 Mar 10. doi: 10.1002/pan.70163. Online ahead of print.

ABSTRACT

BACKGROUND: Sacrococcygeal teratomas (SCT), although rare, are the most common teratomas found in neonates. Anesthetic management of neonates undergoing SCT resection surgery is challenging, given the risk of massive hemorrhage and high mortality rate.

AIMS: The primary aim of this single center retrospective study was to analyze neonates undergoing SCT resection over the last decade and report on perioperative outcomes, including blood product transfusion practices. The secondary aim was to describe patient and tumor characteristics that might place neonates undergoing SCT resection surgery at elevated risk for morbidity and mortality.

METHODS: Retrospective chart review of neonates who underwent sacrococcygeal teratoma resection at Boston Children’s Hospital between January 2012 and April 2024. Demographic data, tumor characteristics, transfusion data, perioperative respiratory and hemodynamic data, and 30-day outcomes were collected. Descriptive statistics for patient and tumor characteristics are reported. Univariate analyses using Fisher’s exact test and the Wilcoxon rank sum test were used for analysis of transfusion data and clinically significant postoperative events.

RESULTS: Seventeen patients were identified. The median age at the time of surgery was day of life 4 with a median weight of 3.3 kg. Thirty-nine percent of neonates experienced a clinically significant postoperative event within 30 days of surgery, defined as a composite outcome event. One patient died within 30 days of surgery. Fifty-nine percent of neonates received an intraoperative blood transfusion. The median transfusion volume of RBCs was 24.8 mL/kg (0, 43). Those transfused had a larger median tumor volume [947.3 cm³ (interquartile range: 354.2, 2048)] and tumor volume-to-weight ratio [0.31 (0.10, 0.77)] compared to those who were not transfused [48.6 cm³ (24.2, 367.5)] and [0.02 (0.01, 0.07)] respectively. The median duration of anesthesia in transfused patients was 7.8 h (6.4, 9.2) versus 5.8 h (3.7, 6.7) in patients not transfused. Although more neonates with non-cystic tumors got transfused (70% vs. 30%), there was no statistically significant difference in median volume of red blood cells transfused intraoperatively for cystic [28.1 mL/kg (0, 40)] versus non-cystic tumors [24.8 mL/kg (0, 60)].

CONCLUSIONS: Neonates undergoing SCT surgery had a high rate of blood transfusion (59%), replacing on average over a quarter of their blood volume, and a high composite adverse outcome rate (39%). Predictors of blood product transfusion include immature tumors, gestational age less than 37 weeks, larger median tumor volume, greater tumor volume-to-weight ratio, higher intraoperative estimated blood loss, and longer time under anesthesia. Predictors of clinically significant postoperative events within 30 days of surgery include Altman type 2 tumors, gestational age less than 37 weeks, and longer anesthesia times.

PMID:41806167 | DOI:10.1002/pan.70163

Ann Clin Transl Neurol. 2026 Mar 10. doi: 10.1002/acn3.70357. Online ahead of print.

ABSTRACT

Paramagnetic rim lesions (PRLs) are a subset of chronic active multiple sclerosis (MS) lesions marked by iron-laden microglia and macrophages. Ocrelizumab, a monoclonal antibody targeting CD20+ B cells, suppresses acute MS activity, but its effect on PRLs remains unclear. In a longitudinal study of 29 ocrelizumab-treated patients with at least one PRL on quantitative susceptibility mapping (QSM), 97 PRLs were identified. Before treatment, PRLs showed higher QSM values than non-PRLs (p = 0.001), indicating iron enrichment. After treatment, PRLs demonstrated a greater QSM reduction (p < 0.001), with an accelerated decline in susceptibility. These findings suggest ocrelizumab may attenuate iron-related inflammation in PRLs.

PMID:41806161 | DOI:10.1002/acn3.70357

Int J Gynaecol Obstet. 2026 Mar 10. doi: 10.1002/ijgo.70930. Online ahead of print.

ABSTRACT

OBJECTIVE: This study evaluates the association between obesity and the presence of bowel endometriosis in patients undergoing surgery.

METHODS: A retrospective cross-sectional observational study was conducted with patients treated between September 2023 and December 2024, at a specialized endometriosis outpatient clinic of a tertiary hospital in Rio de Janeiro, Brazil. Women who underwent surgery for histopathological confirmation of deep endometriosis were included. The outcome was bowel endometriosis, defined as a lesion >1 cm located in the rectosigmoid region. Preoperative weight and height were measured, and obesity was defined according to World Health Organization body mass index (BMI) criteria. The association between obesity and the outcome was assessed using multivariable logistic regression, adjusting for potential confounders. A P-value <0.05 was considered statistically significant.

RESULTS: A total of 223 women with histologically confirmed deep endometriosis were included, of whom 24.2% had bowel involvement. In the multivariable logistic regression, after adjusting for age and number of cesarean deliveries, body weight was independently associated with a lower likelihood of bowel lesions (odds ratio [OR]: 0.97; 95% confidence interval [CI]: 0.94-0.99; P = 0.031). The number of cesarean deliveries was also inversely associated with the outcome (OR: 0.39; 95% CI: 0.21-0.71; P = 0.002).

CONCLUSION: Although higher body weight was associated with a lower chance of bowel involvement, these results should be interpreted cautiously given the cross-sectional nature of the study and the limitations of BMI and body weight as measures of adiposity. Future studies incorporating more precise anthropometric assessments (e.g., bioimpedance, body fat percentage, or abdominal circumference) are warranted.

PMID:41806155 | DOI:10.1002/ijgo.70930

Adv Biotechnol (Singap). 2026 Mar 10;4(1):9. doi: 10.1007/s44307-025-00093-5.

ABSTRACT

Recent advancements in sequencing technologies have transformed the characterization of genomic and transcriptomic complexity. In this review, we present a comprehensive overview of Oxford Nanopore Technologies (ONT), emphasizing its unique capability for real-time, long-read, and direct RNA sequencing. We begin by outlining the core ONT analytical workflow-base calling, alignment, re-squiggling, and quality control-and summarize the major computational tools applied at each stage. Then extensive illustrations of various RNA modification detection techniques are provided, spanning from statistical models, machine learning and deep learning frameworks to advanced strategies incorporating large language models. To assess methodological performance, additional benchmark analyses of m6A and pseudouridine (Ψ) are carried out across two publicly available datasets. These results demonstrate substantial variability across different tools, underscoring the inherent difficulties in reliably detecting modifications from ONT signals. We further examine the biological roles of key RNA modifications and contrast ONT-based approaches with conventional detection technologies. Finally, we discuss persistent limitations such as sequencing error rates, data and computational demands, and the complexity of multi-modification inference, and further propose future directions aimed at improving accuracy, robustness, and biological interpretability in ONT-based epitranscriptomic research.

PMID:41806147 | DOI:10.1007/s44307-025-00093-5

Eur J Clin Microbiol Infect Dis. 2026 Mar 10. doi: 10.1007/s10096-026-05433-4. Online ahead of print.

NO ABSTRACT

PMID:41806099 | DOI:10.1007/s10096-026-05433-4

Eur J Orthop Surg Traumatol. 2026 Mar 10;36(1):136. doi: 10.1007/s00590-026-04691-4.

ABSTRACT

BACKGROUND: The Peroneus longus graft has not been assessed till now in All-Inside Anterior Cruciate Ligament Reconstruction (AI-ACLR). The purpose of this study was to compare the PLT and STT autograft in terms of graft characteristics (e.g. graft diameter, length, etc.) as primary outcome and clinical scores (IKDC, Tegner-lysholm and KOOS scores) as secondary outcomes in AI-ACLR using our modified surgical technique.

MATERIALS AND METHODS: This retrospective, non-randomised case-control study was conducted from January 2021 to October 2023. Patients with ACL tears, aged between 18 and 50 years, were included. Patients having multiligament injuries, fractures, meniscal injuries, pre-existing osteoarthritis of the knee or a BMI of ≥30 kg/m2 were excluded. Patients were non-randomly divided into two groups according to autograft source. Group 1: PLT; Group 2: STT. 70 patients underwent AI-ACLR using our modified technique: Group 1, n = 35; Group 2, n = 35. Mean follow-up duration was 24 ± 3.4 (range 18-28) months.

RESULTS: Mean age was 28 (17-36) years. The harvested tendon length was significantly longer in group 1 (31.51 ± 2.41 mm vs. 29.0 ± 2.49 mm; P = 0.004). Group 1 also had significantly thicker graft diameter (8.9 ± 0.16 mm vs. 8.1 ± 0.3 mm; P = 0.021), longer graft (69.74 ± 1.54 mm vs. 68.18 ± 2.52 mm; P = 0.039), better followup KOOS (68.86 ± 6.1 vs. 60.09 ± 5.65; P < 0.001), Tegner-Lysholm score (69.46 ± 4.62 vs. 65.73 ± 6.25; P = 0.038) and IKDC score (59.26 ± 3.81 vs. 56.18 ± 5.65; P = 0.045). The mean surgical time was slightly less in group 1 (59.89 ± 9.32 min vs. 61.64 ± 6.82 min), but the difference was not statistically significant (P = 0.506).

CONCLUSION: Our modified technique of AI-ACLR using Peroneus longus (PLT) provides better graft characteristics for AI-ACLR as compared to Semi-tendinosis (STT). The functional outcome scores were comparable in both the groups with no major complications reported, at a mean of 24 months of follow-up.

LEVEL OF EVIDENCE III: (Retrospective comparative study).

PMID:41806080 | DOI:10.1007/s00590-026-04691-4