Tag: statistics

Oncologist. 2026 Jul 9:oyag224. doi: 10.1093/oncolo/oyag224. Online ahead of print.

ABSTRACT

BACKGROUND: HER2 amplification identifies a subgroup of colorectal cancer with poorer prognosis and resistance to anti-EGFR therapy. We conducted a systematic review and a metaanalysis of available data on anti-HER2 treatments (HER2Tx) in mCRC patients (pts).

METHODS: A systematic literature search was performed, encompassing phase II/III clinical trials (CTs) investigating HER2Tx in HER2-overexpressed mCRC. CTs reporting HER2Tx plus chemotherapy were excluded. Primary endpoints were objective response rate (ORR) and disease control rate (DCR). Fixed and random-effect models were applied according to heterogeneity assessed through I 2 statistics. Progression free survival (PFS) and overall survival (OS) were compared descriptively and pooled using the weighted median of medians (WM) with approximated 95% CIs. Subgroup analyses by HER2Tx were carried out.

RESULTS: The analysis included 10 CTs evaluating Trastuzumab-Pertuzumab (T + P, 5 CTs,), Trastuzumab Deruxtecan (T-DXd, 2 CTs), Trastuzumab-Lapatinib (T + L, 1 CT), Pertuzumab-TDM1 (P+TDM1, 1 CT), and Trastuzumab-Tucatinib (T-Tu, 1 CT), for a total of 467 pts. The pooled ORR was 33.7% (29.6%-38.1%), and the pooled DCR was 68.5% (58.1%-77.4%). The WM OS was 13.4 months (10-24.1) and WM PFS was 5.5 months (4.1-6.9). The T-DX and T-Tu groups showed higher ORR and DCR (38% and 39% respectively, 85.1% and 73.2% respectively) compared to the T + P group (ORR: 30%, DCR: 52.6%).

CONCLUSIONS: HER2Tx demonstrated efficacy in pretreated CRC pts, exhibiting good DCR and ORR alongside promising PFS and OS. T-DXd and T-Tu appears to outperform T + P; however, further studies are needed.

PMID:42426557 | DOI:10.1093/oncolo/oyag224

Eur Heart J Qual Care Clin Outcomes. 2026 Jul 10:qcag108. doi: 10.1093/ehjqcco/qcag108. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the impact of Continuity of Care (COC)-care provided by the same Primary Care Physician (PCP)-on outcomes in patients with atrial fibrillation (AF).

METHODS: We conducted a retrospective cohort study including all patients with AF referred by PCPs (n=17,889) between January 2010 and December 2023 in the Santiago de Compostela healthcare area (Spain). COC was categorized as “PCP stability” (care by the assigned PCP) or “interrupted COC” (care by multiple rotating PCPs). The association between COC and outcomes (hospitalization, mortality, stroke, and haemorrhage) was estimated using Cox regression and Fine-Gray competing risk models, adjusted for potential confounders.

RESULTS: Patients with PCP stability had a significantly lower annual referral rate (1.5 vs. 1.8, p<0.001) and a higher rate of adequate Oral Anticoagulation (OAC) indication according to the CHA2DS2-VASc score (79.5% vs. 69.1%, p<0.001). COC was independently associated with reduced all-cause mortality (Hazard Ratio [95% CI]: 0.79 [0.69-0.91]), a benefit that remained robust after sensitivity analyses. No significant differences were observed in stroke or haemorrhagic complications; however, competing risk analysis suggests that the higher mortality rate in the interrupted COC group likely precluded the observation of non-fatal events in this high-risk subset.

CONCLUSIONS: Longitudinal COC in Primary Care is associated with improved clinical management, including better OAC indication, and a significant reduction in all-cause mortality among patients with AF. The survival benefit of seeing the same physician appears to extend beyond anticoagulation optimization, highlighting the pleiotropic value of the patient-physician relationship.

PMID:42426552 | DOI:10.1093/ehjqcco/qcag108

Metabolomics. 2026 Jul 9;22(4):123. doi: 10.1007/s11306-026-02504-7.

ABSTRACT

INTRODUCTION: Saliva biomarker research requires understanding of how saliva collection and processing techniques affect results and reproducibility. Direct comparison of the effect of processing and storage conditions on downstream assay outcomes is important to understanding the ways that delay in freezing, methods of freezing, filtration protocols, and other factors can affect results and thus, interpretations about stress response and adaptation. This type of study compliments the work that is required to understand how saliva compares to tissue and blood responses and what the implications of changes in saliva biomarkers mean to our understanding of biomarkers of stress during exercise and environmental stress exposures.

OBJECTIVE: In this pilot study, we evaluated the effects of different processing methods on metabolomics results and discuss the implications of these findings for future experimental design.

METHODS: We assessed the effects of centrifugation, time-of-day collection, filtration, and mucinase treatments and determined that there are quantifiable differences in metabolomics results with different treatments.

RESULTS: Adding processing steps did not increase the number of metabolites detected or the sensitivity and specificity of results.

CONCLUSION: Comprehensive descriptions of methods in this area will support better interpretation and reproducibility in this field.

PMID:42426550 | DOI:10.1007/s11306-026-02504-7

Acta Neurol Belg. 2026 Jul 10. doi: 10.1007/s13760-026-03134-5. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The predictive value of the atherogenic index of plasma (AIP) and high-sensitivity C-reactive protein (hsCRP) for stroke is established; however, evidence is largely derived from diabetic cohorts, limiting the generalizability of findings to non-diabetic populations. We therefore conducted this study to specifically assess their combined and interactive associations with stroke in individuals without diabetes.

METHODS: This study included 8,721 participants from the CHARLS baseline (wave1) with no history of stroke or diabetes at baseline. The AIP was calculated as lg[Triglycerides (mmol/L)/HDL-C(mmol/L)]. In a subset of 5,763 participants with repeated measurements, we further analyzed the associations of CumAIP and CumhsCRP with incident stroke.

RESULTS: The results showed that compared to individuals with both low AIP and low hsCRP, those with elevated levels of both had the highest overall risk of stroke (adjusted Hazard Ratio [aHR]: 1.715; 95% Confidence Interval (CI): 1.380-2.130). Compared with the traditional risk factor model, the model adding AIP and hsCRP improved the AUC from 0.664 to 0.673 (P < 0.05), with a continuous Net Reclassification Improvement (NRI) of 0.182 (95% CI: 0.075-0.289) and Integrated Discrimination Improvement (IDI) of 0.009 (95% CI: 0.003-0.015).A total of 435 stroke events were observed during the 5-year follow-up subanalysis, individuals with high levels of both cumulative exposures also had a significantly increased risk (aHR: 1.421; 95% CI: 1.133-1.783).Furthermore, using repeated measurements, mediation analyses demonstrated no statistically significant mediating effect of hsCRP in the association between AIP and stroke. In contrast, AIP exerted a significant mediating effect, accounting for 11.6% of the total effect of hsCRP on stroke.

CONCLUSIONS: The study findings confirm that AIP and hsCRP exert combined effects on stroke risk among non-diabetic middle-aged and older adults. Notably, AIP plays a significant mediating role in the association between elevated hsCRP and stroke. Therefore, integrating both markers into risk assessment is recommended to refine primary stroke prevention and address residual risk among non-diabetic populations, particularly middle-aged adults.

PMID:42426492 | DOI:10.1007/s13760-026-03134-5

Aesthetic Plast Surg. 2026 Jul 9. doi: 10.1007/s00266-026-06144-z. Online ahead of print.

NO ABSTRACT

PMID:42426478 | DOI:10.1007/s00266-026-06144-z

Methods Mol Biol. 2026;2999:183-201. doi: 10.1007/978-1-0716-5050-9_15.

ABSTRACT

The purpose of this chapter is to provide a comprehensive, step-by-step methodology for the analysis of circulating tumor cell (CTC) interactions within the blood microenvironment, from the acquisition of CTCs to single-cell transcriptomic sequencing and subsequent data analysis. Our methodological approach involved the following steps: (1) Data Preprocessing: The raw sequencing data were subjected to stringent quality control and preprocessing to remove artifacts and outliers that could potentially skew the analysis. (2) Seurat analysis: Utilizing the Seurat package, we performed dimensionality reduction techniques such as principal component analysis (PCA), t-Distributed Stochastic Neighbor Embedding (t-SNE), and uniform manifold approximation and projection (UMAP) to visualize and cluster CTCs based on their gene expression profiles. (3) CellphoneDB integration: We employed CellphoneDB to analyze the interactions between CTCs and other cell types within the blood, elucidating potential interaction pairs that could be targeted for therapeutic intervention. (4) Statistical graphics: The ggplot2 package was used to create informative and visually appealing graphs that summarized the results of our analysis, facilitating the interpretation of complex data for both oncologists and biologists. By following this methodological framework, we were able to provide a comprehensive analysis of CTC interactions, offering valuable insights that could inform the development of targeted therapies in oncology.

PMID:42426458 | DOI:10.1007/978-1-0716-5050-9_15

Pharm Res. 2026 Jul 9. doi: 10.1007/s11095-026-04143-y. Online ahead of print.

ABSTRACT

PURPOSE: Systematic covariate modeling in nonlinear mixed-effects (NLME) analysis is computationally intensive due to repeated refitting to concentration-time data. Although empirical Bayes estimates (EBEs) facilitate screening, η-shrinkage attenuates between-subject variability and distorts covariance structures, leading to shrinkage bias. We propose a variance-consistent framework enabling covariate modeling from a single base-model fit.

METHODS: The proposed approach incorporates subject-specific posterior means and covariances from an NLME base model. A variance-matching penalty enforces consistency between the total between-subject covariance (model-explained and unexplained) and the base model estimates, preserving the covariance structure without refitting. Performance was compared with EBE regression, two-stage Bayesian estimation, and NLME covariate modeling. Stepwise covariate selection was evaluated using likelihood ratio tests, with the resulting structure compared against the NLME-identified structure as the gold-standard reference.

RESULTS: Under substantial η-shrinkage of approximately 30%, EBE regression and two-stage Bayesian estimation attenuated covariate-effect parameter estimates. The proposed method provided unbiased estimates, mitigating shrinkage bias and recovering covariate-effect parameter estimates obtained with NLME. It also reproduced NLME-based stepwise covariate selection with high computational scalability by avoiding repeated refitting to time-course data.

CONCLUSIONS: Variance-consistent posterior-based covariate modeling provides a statistically coherent and computationally scalable framework for systematic covariate identification in population PKPD analysis.

PMID:42426415 | DOI:10.1007/s11095-026-04143-y

Arch Orthop Trauma Surg. 2026 Jul 9;146(1):251. doi: 10.1007/s00402-026-06411-3.

ABSTRACT

INTRODUCTION: Periprosthetic joint infections (PJIs) complicate 1-2% of primary and up to 4% of revision arthroplasties, and their diagnosis remains challenging due to the lack of a diagnostic gold standard. Differentiating PJI from aseptic failure is particularly difficult in low-grade or biofilm-related infections. Routine intraoperative microbiological screening is not recommended in presumed aseptic revisions. This study aimed to evaluate the association between routine intraoperative microbiological screening and implant survival in presumed aseptic revision arthroplasty. A secondary objective was to identify preoperative predictors of unexpected PJIs.

METHODS: Retrospectively collected data of patients undergoing presumed aseptic THA and TKA revisions between 2013 and 2019 were included. Two matched cohorts were compared: a screened group (2016-2019) undergoing routine intraoperative microbiological sampling, and an unscreened one (2013-2015) without systematic screening. Kaplan-Meier survival analysis with log-rank testing assessed overall and infection-free survival. Univariate conditional logistic regression and receiver operating characteristic (ROC) analyses evaluated potential associations between preoperative serum markers and unexpected PJI.

RESULTS: A total of 559 patients were included, of whom 295 underwent screening and 264 did not. Unexpected infections occurred in 20.3% (n = 60) of screened patients. No significant differences in implant survival were observed between groups. Although overall and infection-free survival were numerically higher in the screened cohort, these differences were not statistically significant (p = 0.168 and p = 0.118, respectively). Stratified analyses by joint and failure mechanism showed comparable findings. C-reactive protein and erythrocyte sedimentation rate were associated with unexpected PJI (p = 0.004 and p = 0.046), but ROC analysis suggested limited discrimination of individual markers, whereas a combined serum model improved diagnostic performance (AUC = 0.833).

CONCLUSIONS: Routine intraoperative microbiological screening in presumed aseptic revision arthroplasty was not associated with a significant improvement in implant survival. Future studies should investigate whether selective screening improves outcomes. Level III retrospective cohort study.

PMID:42426411 | DOI:10.1007/s00402-026-06411-3

Surg Endosc. 2026 Jul 9. doi: 10.1007/s00464-026-13107-7. Online ahead of print.

ABSTRACT

BACKGROUND: The Area Deprivation Index (ADI) is an important measure of neighborhood-level socioeconomic status (SES). Our study evaluates the correlation of ADI scores to post-operative clinic follow up compliance and completion of pre-operative high-resolution manometry (HRM) in patients with Achalasia undergoing Peroral Endoscopic Myotomy (POEM).

METHODS: We conducted a retrospective cohort study of adult patients undergoing POEM at a single tertiary care center between March 2017 and December 2024 (N = 193). ADI was assigned using 2023 national rankings based on patient residential addresses. Analyses were restricted to patients with available ADI data (n = 181). Multivariable logistic regression was performed adjusting for age, travel distance, sex, body mass index (BMI), and smoking status.

RESULTS: Patients who did not complete pre-operative HRM had higher ADI scores (89 [IQR 21]) compared to those who did (85 [IQR 29]), (p = 0.015). Patients who did not attend initial or overall post-operative follow-up also had higher ADI scores compared to those who completed follow-up. Median ADI was higher among patients with incomplete initial follow-up (90 [IQR 17] vs 85 [IQR 28]; p = 0.068) and overall follow-up (91 [IQR 18] vs 85 [IQR 27]; p = 0.064); however, these differences did not reach statistical significance on non-parametric testing. Mean values demonstrated similar patterns but were statistically significant on parametric analysis (p = 0.010 and p = 0.013, respectively). In multivariable logistic regression analysis, higher ADI rank was independently associated with increased odds of failing to complete pre-operative HRM (OR 1.04, 95% CI 1.01-1.07, p = 0.005). Age, travel distance, sex, BMI, and smoking status were not significantly associated with HRM completion (all p > 0.05).

CONCLUSION: Patients with higher ADI scores were less likely to complete HRM pre-operative testing. ADI scores can be used as a measure to risk stratify Achalasia patients undergoing POEM.

PMID:42426394 | DOI:10.1007/s00464-026-13107-7

Surg Endosc. 2026 Jul 9. doi: 10.1007/s00464-026-13090-z. Online ahead of print.

ABSTRACT

BACKGROUND: Oligometastatic prostate cancer (omPC) represents a specific state with improved outcomes following cytoreductive radical prostatectomy (cRP). Prognostic factors that guide disease progression are yet to be fully elucidated, and the role of pelvic lymph node dissection (LND) in this setting is controversial. This study aimed to evaluate the impact of LND on biochemical progression and castration-resistant prostate cancer (CRPC) in patients with omPC.

METHODS: A total of 169 omPC patients who underwent cRP with (n = 123) or without LND (n = 46) between January 2015 and February 2024 at multiple centers were retrospectively analyzed. Biochemical progression-free survival (bPFS) and time to CRPC were analyzed using Kaplan-Meier curves and Cox proportional hazards models. Subgroup analysis stratified by nodal status was performed to explore differential treatment effects.

RESULTS: In the overall cohort, multivariable analysis identified initial PSA > 30 ng/mL as an independent predictor of biochemical progression (HR = 2.53, 95% CI: 1.40-4.58, p = 0.002). For CRPC progression, no variable reached conventional statistical significance in the multivariable model. Stratified analysis revealed that among patients with node-positive disease (N1, n = 40), LND was associated with significantly prolonged bPFS (p = 0.018) and delayed progression to CRPC (p = 0.014). Notably, within the LND cohort (n = 123), N1 patients had significantly higher Gleason scores and T stages, and experienced worse CRPC than N0 patients (p = 0.02).

CONCLUSION: In omPC patients undergoing cRP, high baseline PSA independently predicted biochemical recurrence. Nodal involvement was associated with more aggressive disease features and worse outcomes within the population. An exploratory subgroup analysis suggested that node-positive patients may be associated with improved outcomes after LND; however, this finding was limited by a very small sample size and requires prospective validation.

PMID:42426390 | DOI:10.1007/s00464-026-13090-z