Background: Prediabetes is characterized by impaired glucose regulation and altered redox homeostasis, which may contribute to progression to type 2 diabetes. Polyphenol-rich foods may improve metabolic and redox balance. Methods: Fifty-four women aged 30-60 years with prediabetes were randomly assigned to an intervention group (IG) or control group (CG); 50 completed the 12-week study (25 per group). Both groups received Mediterranean diet recommendations. The IG additionally consumed 100 mL/day of chokeberry juice, providing 457 mg GAE of total polyphenols and 9.7 mmol antioxidant capacity (FRAP), whereas the CG received no study product. Fasting plasma glucose (FG), HbA1c, 2 h plasma glucose (2h-PG), total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) were assessed at baseline and 12 weeks. Between-group differences in individual changes were analyzed using the Mann-Whitney U test with Benjamini-Hochberg false discovery rate correction. The randomized substudy reported here was conducted within the broader single-group parent study registered at ClinicalTrials.gov (NCT06435130), which enrolled a larger mixed-sex cohort; the present analysis concerns only the nested 12-week randomized comparison in women with prediabetes. Results: Compared with the CG, the IG showed greater reductions in FG, HbA1c, 2h-PG, TOS, and OSI and a greater increase in TAS. All between-group differences remained significant after FDR correction (adjusted p < 0.001), with large Cliff's delta values. Conclusions: Adding 100 mL/day of chokeberry juice to Mediterranean diet recommendations for 12 weeks was associated with modest but statistically significant improvements in glycemic and redox-related outcomes in women with prediabetes. The small sample, short follow-up, and lack of placebo control limit generalizability; larger, longer placebo-controlled trials are warranted.

Serrated polyposis syndrome (SPS) is the most common form of colorectal polyposis syndrome. Most SPS cases are sporadic, and the environmental factors underlying its pathogenesis remain poorly defined. Intestinal spirochaetosis (IS), an infection of the colonic epithelium by Brachyspira species, is frequently asymptomatic and its clinical relevance is uncertain. Here, we examined the potential association between IS and SPS.

In this retrospective case-control study at two centres in Japan, IS prevalence was assessed in 64 patients with SPS and 382 non-SPS controls who underwent colonoscopic polypectomy. Controls were classified as having only conventional adenomas (Ctrl-CA) or serrated polyps not meeting the diagnostic criteria of SPS (Ctrl-SP).

Histologically confirmed IS was detected in 12/64 (18.8%) SPS cases and 6/382 (1.6%) controls (OR 14.5, 95% CI 5.2 to 40.2; p<0.001). IS prevalence increased stepwise across Ctrl-CA, Ctrl-SP and SPS groups (1/274 (0.4%), 5/108 (4.6%) and 12/64 (18.8%), respectively; OR 6.5, 95% CI 3.1 to 13.8; p for trend <0.001). Among the 12 IS-positive SPS cases, all had a history of cigarette smoking and altered bowel habits were common. Furthermore, IS detection rates did not differ based on anatomical locations of polyps, but considerable intraindividual variability was observed across serial colonoscopies, suggesting possible episodes of clearance and reinfection. Real-time PCR and sequencing analyses demonstrated that all IS-positive cases were attributable to Brachyspira aalborgi, a species commonly found in developed countries.

This study reveals a novel association between IS and SPS with distinct clinical characteristics in Japan. Considering the retrospective design and small sample size from a single geographic region, further investigation is required to clarify the significance and generalisability of this association.

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is the only curative approach for adult T-cell leukemia-lymphoma (ATL). However, preventing post-transplant relapse remains challenging. While pre-transplant disease status is known to be associated with post-transplant outcomes, the impact of residual disease (RD) localization at the time of allo-HCT has not been well described. In this retrospective study of 33 patients with aggressive ATL who underwent allo-HCT, patients were classified into two risk groups based on RD sites: a low-risk group (no lymph node [LN] or extranodal [EN] disease, regardless of the presence of peripheral blood disease) and a high-risk group (presence of LN and/or EN disease). The low-risk group had significantly superior overall survival (OS) and progression-free survival (PFS) compared to the high-risk group, with longer median survival times (OS: 1953 vs. 245 days; PFS: 1177.5 vs. 72 days) and higher 2-year survival rates (OS: 65.0% vs. 11.3%; PFS: 50.0% vs. 8.3%) (p = 0.012 and p = 0.013, respectively). Furthermore, even among patients who had not achieved complete response, RD localization stratified the survival outcomes: the 2-year OS and PFS were 75.0% and 75.0% in the low-risk group, compared with 11.3% and 8.3% in the high-risk group, respectively. In conclusion, RD localization at the time of allo-HCT is a novel prognostic factor, highlighting the need for tailored pre-transplant management for ATL.

Patients with cervical cancer or High-Grade Squamous Intraepithelial Lesion (HSIL) often experience mental problems such as anxiety and depression. Online mindfulness-based interventions offer accessible mental health support. However, evidence for cervical cancer or HSIL patients remains scarce, and evaluations often rely solely on self-reported scales, with a lack of neurophysiological assessments. This study aimed to assess the effectiveness of a 6-week online mindfulness-based intervention on mental health outcomes in this population by using scales, with exploratory frontal electroencephalogram (EEG) biomarkers as supplementary neurophysiological indicators.

A single-center randomized controlled trial enrolling 151 cervical cancer or HSIL patients was conducted. The intervention group received a 6-week online mindfulness-based intervention, while the control group received general mental health education. Primary outcomes were depressive and anxiety symptoms assessed by validated scales. Frontal EEG metrics were collected as exploratory supplementary neurophysiological indicators. Assessments were conducted at baseline and post-intervention. Independent samples t-tests and Mann-Whitney U tests were used for intergroup comparisons, with Benjamini-Hochberg FDR correction applied to control for multiple testing.

A total of 149 patients completed the study. After the intervention, the intervention showed significantly lower symptoms of depression (t = 12.238, FDR-q < 0.001), anxiety (t = 11.150, FDR-q < 0.001), and higher levels of resilience, mindfulness, and perceived social support than the control group. Exploratory EEG analysis revealed that the intervention group exhibited higher relative theta and alpha power, higher time-domain standard deviation, and lower relative beta and gamma power than the control group.

This study demonstrates that a 6-week online mindfulness-based intervention effectively alleviates depressive and anxiety symptoms among patients with cervical cancer or HSIL. Exploratory EEG findings provide preliminary neurophysiological support for these psychological benefits, though further validation with larger samples is warranted.

The trial was prospectively registered on the Chinese Clinical Trial Registry (ID: ChiCTR2400087926, https://www.chictr.org.cn/) on August 07, 2024.

To investigate the incidence and risk factors of myocardial injury after noncardiac surgery (MINS) in oncology patients undergoing surgery for medication-related osteonecrosis of the Jaw (MRONJ).

This retrospective study analyzed 65 patients with oncology-related MRONJ who underwent surgical treatment between October 2024 and May 2025. High-sensitivity cardiac troponin I (hs-cTn I) levels were measured preoperatively and within 72 h postoperatively. MINS was diagnosed according to established criteria. Clinical characteristics were compared and analyzed between patients with and without MINS to evaluate associations among relevant variables.

Among the 65 patients, 7 (10.8%) developed MINS. Compared with patients without MINS, those with MINS had a significantly lower body mass index (BMI; P = 0.003), a higher prevalence of preoperative myocardial injury (P = 0.005), lower preoperative serum albumin levels (P = 0.039), and a significantly more severe anemia (P = 0.029). Spearman correlation analysis demonstrated a moderate positive correlation between MINS and preoperative myocardial injury (ρ = 0.435, P < 0.001) and a negative correlation between MINS and BMI (ρ = - 0.366, P = 0.003). Significant correlations were also observed among BMI, serum albumin levels, and anemia severity, suggesting an interaction between nutritional status and postoperative myocardial injury in MRONJ patients.

In this exploratory study, MINS in oncology-related MRONJ patients was observed to be associated with preoperative myocardial injury, low BMI, hypoalbuminemia, and anemia. These preliminary findings suggest that incorporating nutritional assessment and cardiac biomarker surveillance into perioperative evaluation may support risk stratification. However, these observed associations require confirmation in larger, prospective studies.

Osteosarcoma remains challenging in metastatic, recurrent, or therapy-resistant disease. This study aimed to identify senescence-related prognostic genes and characterize their spatial contexts. Paired differential expression analysis was performed in GSE99671 using DESeq2, followed by intersection with the CellAge senescence gene set. Transcriptomic data from the TARGET-OS cohort were obtained from UCSC Xena. Candidate genes were evaluated using univariate Cox regression, Kaplan-Meier analysis, time-dependent receiver operating characteristic analysis, LASSO Cox regression, repeated LASSO analysis, and random survival forest modeling, with clinical covariates incorporated into adjusted Cox models. Functional enrichment, immune microenvironment analysis, single-cell transcriptomics, SP_BS3 spatial transcriptomics, GSE36001 expression validation, and qRT-PCR and Western blot validation in osteosarcoma 143B cells and osteoblast cells were used to characterize it. In GSE99671, 2,248 genes were differentially expressed with adjusted P < 0.05, and their intersection with the 866 CellAge genes yielded 105 senescence-related differentially expressed genes. In TARGET-OS, lower PPARG expression was associated with a higher mortality risk (univariate HR = 0.603, 95% CI = 0.454-0.802, P = 0.000494; adjusted HR = 0.224, 95% CI = 0.085-0.589, P = 0.00241). Adding PPARG to the clinical model increased the C-index from 0.707 to 0.829. PPARG was downregulated in both GSE99671 and GSE36001, and qRT-PCR and Western blotting confirmed lower PPARG mRNA and protein expression in osteosarcoma 143B cells than in osteoblast cells. Single-cell analysis localized PPARG to endothelial cells, pericytes, macrophages/monocytes, and tumor-associated stromal cells. Spatial transcriptomic analysis showed weak but significant positive correlations between PPARG expression and the CellAge senescence, endothelial-related, and pericyte-related scores. These findings nominate PPARG as a candidate CellAge-derived prognostic biomarker associated with unfavorable survival and vascular microenvironmental features in osteosarcoma and support investigation of its potential relevance to risk stratification and the senescence-related tumor microenvironment. GSE36001 provided external expression validation only; independent survival validation was not performed.

Stomach cancer (SC) is the third leading cause of cancer-related death in China, imposing a substantial burden on the healthcare system. Nutritional risk is common among patients with SC, yet evidence on associated medical costs and their composition remains limited in China. This retrospective observational study estimated SC-related medical costs and cost composition by preoperative nutritional status. Medical treatment costs were obtained for inpatients aged ≥18 years who were primarily diagnosed with SC and underwent surgical treatment between 2020 and 2023 at a tertiary hospital in Ningbo, China. Preoperative nutritional status was assessed using Nutrition Risk Screening 2002, classifying patients as at nutritional risk or well-nourished. Total treatment costs were categorized into five components: examination, surgery, medication, material, and hospital service costs. All costs were converted to 2020 Chinese yuan. Among 1,102 patients, 69.51% were male, 69.06% had stage I-II disease, and 50.18% were at nutritional risk. Materials, medications, and examinations accounted for 70%-75% of total costs, depending on year and nutritional status. From 2020 to 2023, the proportions of examination, surgery, and hospital service costs increased, while material costs declined at comparable rates in both groups. Medication cost proportions decreased in both groups; descriptively, the annual decrease was larger among well-nourished patients (-2.85% vs. -0.96%), although this between-group difference was not formally tested. In conclusion, SC-related medical costs varied across preoperative nutritional statuses. Subsidies for essential medications and medical materials may be considered to reduce the economic burden of SC treatment. The economic implications of nutritional support should be further evaluated in future studies with detailed information on nutritional interventions and their costs.

The premise of personalized medicine is that patients exhibit significant heterogeneity and respond differently to treatments. The best treatment for one patient may not be suitable for another. In this paper, we propose a Bayesian adaptive design for an avatar-driven clinical trial, using mouse or laboratory animal grafts to create personalized tumor models that guide individualized patient treatment while accounting for translational discrepancy between avatars and patients. We jointly model the tumor growth of avatars and the clinical outcomes of patients, including toxicity and progression-free survival, to capture the interplay between avatars and their source patients. This joint model enables us to leverage both avatar treatment responses and patient data to predict the treatment utility for each patient and inform the selection of personalized optimal treatments, thereby serving as a digital twin of the patient. To address the fact that avatars may only serve as valid surrogates for treatment effects in a subset of patients, we incorporate a latent-class model that accounts for this translational discrepancy. Through simulation studies, we demonstrate that the proposed design outperforms conventional clinical trials lacking avatar information. Under this design, patients are significantly more likely to receive personalized optimal treatments, leading to improved treatment outcomes.

Long-term overall survival (OS) extrapolations underpin cost-effectiveness appraisals, projecting survival beyond trial follow-up. We aimed to compare extrapolations presented in manufacturer submissions and appraisals published by the Swedish Dental and Pharmaceutical Benefits Agency (TLV) with extrapolations using OS data with longer follow-up available after the original appraisal.

We retrieved publicly available appraisals for oncology compounds from 2009 to 2019. For each appraisal, Kaplan-Meier curves of OS and base case extrapolation assumptions were collected. Longer-term OS data were identified through literature review and supplemented by manufacturers, then digitized to create pseudo-individual patient data. The extrapolation approach used in each appraisal was reapplied on the follow-up data cut to produce long-term OS predictions. Predictions from the original and follow-up data cuts were compared by area under the curves (AUC) and Akaike information criterion (AIC)-based ranking.

Forty reports were included. The average duration of the original data cut was 28.1 months. Using the follow-up data cut, with an average follow-up of 54.2 months, the average AUC of extrapolated OS estimates increased by 8.8% (95% CI 5.2% to 12.6%) under TLV assumptions and by 10.9% (95% CI 6.9% to 15.1%) under manufacturer assumptions. Thirteen (33%) TLV cases and 14 (35%) manufacturer cases showed AUC increases greater than 10%. In the AIC model-rank analysis, 18 models ranked worse when fitted to the longer-term data than to the original data, 16 ranked the same or better, and six were excluded.

Long-term survival estimates generally increased when original assumptions were applied to follow-up OS data, with material increases (>10%) in roughly one-third of cases, indicating original extrapolations were frequently conservative for the active arm. The findings support revisiting survival model fit, treatment-waning assumptions, and alternative scenarios when longer-term data become available. Validation across both arms is warranted to assess incremental outcomes and cost-effectiveness.

Colorectal cancer outcomes are heterogeneous, so greater prognostic discrimination is needed. In this retrospective real-world analysis, we assessed the prognostic effect of markers of systemic inflammation in a cohort of patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC) who received anti-EGFR therapy during routine care. We further examined the association between these markers and the known predictive biomarkers of anti-EGFR efficacy, amphiregulin (AREG) and epiregulin (EREG).

The prognostic effects of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) were tested. The cohort was randomly partitioned into training and validation sets (1:1). Cutoff values were defined in the training set, with analyses repeated in the validation set. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate and disease control rate.

374 patients with RAS and BRAF wild-type mCRC who received treatment with cetuximab or panitumumab across eight UK centres were included. NLR (≤ 4 vs. > 4) and PLR (≤ 200 vs. > 200) were independently prognostic for both OS and PFS. SII (≤ 900 vs. > 900) gave the strongest prognostic signal (OS: adjusted HR 1.63 [1.26-2.11], p = 0.0002 and PFS: adjusted HR 1.62 [1.26-2.08], p = 0.0001). There were no associations between NLR or PLR with AREG or EREG, suggesting anti-EGFR benefit in AREG/EREG-high tumours is not related to systemic inflammation.

Routinely assessed markers of systemic inflammation are independently prognostic in patients with mCRC receiving anti-EGFR therapy and may serve as useful adjuncts in informing discussions with patients about prognosis.